Dr. Brechot's Health Research & Care Blog - October 28, 2022

Visit the Global Virus Network Resource Portal for the latest scientific answers to your questions about COVID-19 variants and vaccines.

October 28, 2022

Holiday is coming, are you ready for the new Omicron subvariants?

It’s been a few months since the last blog update. During this time, the outbreak of monkeypox has caught people’s attention. The Global Virus Network representing 69 Centers of Excellence and 11 Affiliates in 37 countries and comprising foremost experts working on every class of human virus have formed the GVN Monkeypox Task Force. It urgently brought together GVN researchers to explore how to fight against the growing number of monkeypox cases worldwide. GVN has also launched a webpage that offers full information on this important issue. While the global monkeypox outbreak has been receding, the COVID-19 pandemic continues, and we are living in the Omicron variant era. With holiday season around the corner, what should we know and what should we do?

What we know about the Omicron subvariants

BA.5, BA 4.6, and BF.7

Based on the estimate from the U.S. Centers for Disease Control and Prevention (CDC) on last Friday, Omicron’s BA.5, which has been the main strain of COVID-19 cases in the United States for several months, is still in the lead (49.6%). Currently, BA 4.6 and BF.7 account for 9.6% and 7.5% COVID-19 cases in the U.S., respectively. Because of its unique spike protein mutation cluster, BA.5 is one of the most susceptible omicron lineages to breakthrough infections. The good news is that it doesn’t cause more severe symptoms than the other variants.

BQ.1 and BQ.1.1

The prevalence of Omicron subvariants BQ.1 and BQ.1.1 increased to 27% in the United States. It was reported 5% two weeks ago. The two variants are descendants of Omicron’s BA.5 subvariant. A preprint published last week showed that BQ.1 and BQ.1.1 have enhanced neutralization resistance in all new subvariants, driven by a key N460K mutation. We need to keep an eye on these two variants, as they seem to be spreading quickly.

XBB

Last week, the World Health Organization reported that the recombinant variant XBB, which has been on a rise in Singapore and other parts of Southeast Asia, has been found in more than 26 countries. According to a recently published Preprint on BioRxiv, XXB is the strain with the highest antibody avoidance against existing antibody drugs, including Evusheld and Bebtelovimab. The CDC is also keeping a track of XBB in the United States; yet there has been so far not report of severe associated diseases. However, further studies need to be done to confirm whether or not XBB will induce the next wave of COVID-19 cases.

What should we do?

Holiday season is coming which means flu and Respiratory Syncytial Virus (RSV) season are right around the corner as well. Many of you are planning to travel or visit your loved ones during the holiday; what can we do to protect them and yourself? This month, U.S. Food & Drug Administration authorized the use of COVID-19 Bivalent Vaccine Booster dose. The booster dose can provide protection against the original strain as well as the Omicron variant. Moderna COVID-19 vaccine bivalent single dose was approved for use in individuals 6 years of age and older, and the Pfizer-BioNTech one was approved for use in individuals 5 years of age and older. Both bivalent booster doses should only be used at least two months after completing COVID-19 primary or booster vaccination. Eligible individuals are strongly encouraged to receive the bivalent vaccine. Everyone 6 months and older in the United States should get a flu shot every season, with a few exceptions, to protect you from the flu virus. It is also recommended to wear a mask in crowded indoor space. Good personal hygiene also plays an important role in preventing infection with SARS-COV-2 and/or influenza.

Christian Brèchot, MD, PhD
Senior Associate Dean for Research in Global Affairs, USF Health Morsani College of Medicine
Associate Vice President for International Partnerships and Innovation, USF
Professor, Department of Internal Medicine
President, Global Virus Network

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

April 27, 2022

SARS-Cov-2 Omicron Variant Keeps Surprising Us with Its Continuous Evolution

Earlier this year, Omicron BA.2 quickly became the dominant variant in the United States, infecting many people. Another subvariant BA.2.12.1, has been counted in more than 19% of new cases, according to data recently released by the U.S Centers for Disease Control and Prevention. Little is known about this subvariant, but it does appear to be highly contagious; yet fortunately it does not appear to cause severe symptoms. Dr. Emma Thomson, Professor of MRC-University of Glasgow Centre for Virus Research at London School of Hygiene and Tropical Medicine, and a member of the Global Virus Network recently conducted an excellent seminar about “the Characterizing the Omicron Variant of SARS-CoV-2”, which you can view here.

After months of mutation, the Omicron variant of SARS-COV-2 keeps surprising us by constantly evolving. Now the Omicron variant of SARS-COV-2 has further mutated and expanded into several lineages. According to a recent report from the World Health Organization (WHO), the Omicron variant includes B1.1.529, BA.1, BA.2, BA.3, BA.4, BA.5 and descendent lineages. It also includes XE, an Omicron variant recent emerged after recombination of Omicron BA.1 and BA.2. More than 1,000 cases have been reported in the UK, based on the recent report from the UK Health Security Agency. Japan, India, Australia, Spain and other countries have also reported their first cases of the XE mutation in the past few weeks. WHO emphasizes that public health authorities should monitor these descendant lineages as distinct lineages and should conduct comparative assessments of their viral characteristics. So, in order to better understand the viral characteristics of different variants and lineages, we first need to understand how XE occurs.

What is the recombination?

In our last blog post, we briefly introduced the concept of Deltacron variants. Delatacron is a recombinant virus between the Delta and Omicron variants. Recombination occurs when the two variants become infected and replicate in the same person and cells. Deltacron is the result of two variants of Delta and Omicron that spread and infect in the same population.

XE occurs in a similar process. The only difference is that Deltacron is a recombination of two different variants — Delta and Omicron. XE is a recombination of Omicron’s own BA.1 and BA.2 lineages. In other words, XE combines the genetic characteristics of Omicron BA.1 and BA.2 strains. Is XE more contagious than other lineages? It is too early to draw conclusions at this point. However, one of WHO’s Weekly Epidemiological Update On COVID-19 Report shows that XE represents a 10% transmission advantage as compared to BA.2. However, further research is needed to confirm the findings. Monitoring for this disease and other emerging mutations is critical to ending the pandemic.

Will the vaccine work against all the new mutated strains?

The short answer is yes. Despite all the uncertainties, existing COVID-19 vaccines are providing protection against severe illness, hospitalizations and reducing community transmission. In particular, the booster shot will increase the protection against the spread of the Omicron variants. We also need to continue to reduce the spread of the virus through necessary testing and self-isolation. We all know that Omicron will not be the last variant of SARS-CoV-2 as long as cases continue to circulate. What we can do is to increase the vaccination rates among populations, especially in countries where they have limited access to vaccines. The importance of SARS-COV-2 vaccination equity is self-evident. It is not too late to reach global vaccine equity. Organizations like WHO and Gavi, the Vaccine Alliance are working towards vaccine equity to leave no one behind.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

March 10, 2022

Omicron BA.3 lineage and Deltacron update

In our last blog we briefly introduced the Omicron variant (B.1.1.529) and its subvariants BA.1 and BA.2. A month later, the Omicron family has expanded to three globally prominent subvariants, BA.1, BA.2 and BA.3. So, what are the characteristics of BA.3 lineage?

The BA.3 lineage was discovered in northwestern South Africa. Based on a preprint paper recently published on bioRxiv, BA.1 has 39 mutations, BA.2 has 31, and BA.3 has 34, with 21 shared mutations among all three. BA.2 now accounts for 11% of COVID-19 cases in the United States according to the Centers for Disease Control and Prevention. BA.3 spreads much slower than either BA.1 or BA.2. This is likely due to the missing mutations compared to BA.1 and BA.2.

Real-world data from South Africa, the United Kingdom (UK), and Denmark indicate no difference in severity between Omicron subvariants BA.2 and BA.1, according to the World Health Organization (WHO). High levels of immunity from vaccination or infection could contribute to this outcome. Even though Omicron is known for causing milder illness than previous variants, more studies are needed to understand the severity of BA.3.

Deltacron: A real variant or lab error?

In early January, a scientific team announced the discovery of several SARS-COV-2 genomes that featured elements of both the Delta and Omicron variants and called the hybrid “Deltacron.” A few days later, the scientists clarified that what they found likely resulted from a contamination in the laboratory. Since then, however, Deltacron cases arising from genetic sharing of information (recombination) between the Omicron and Delta strains have been fully confirmed.

In the UK, health officials identified a patient infected with both Delta and Omicron at the same time. The UK Health Security Agency continues to monitor the situation.

France has reported 10 cases of Deltacron infection. According to the global initiative GISAID, the first solid evidence for a Delta-Omicron recombinant virus was shared by Institut Pasteur Paris via a GISAID analysis of raw genomic data. This analysis clearly confirmed the structure of recombinant viruses from the Delta AY.4 and Omicron BA.1 lineages. The recombinant virus identified by EMERGEN Consortium in several regions of France has been circulating since early January 2022, and genomes with similar characteristics were also found in Denmark and the Netherlands. However, much remains unclear. Scientists around the globe should collaborate to better understand Deltacron’s infectivity, transmissibility, disease severity and immune evasion.

What’s next?

As the virus continues to mutate, more variants of concern may emerge, and SARS-COV-2 will remain. So, as we’ve emphasized before, if you qualify, get vaccinated! Vaccines can protect against severe illness from COVID-19. When needed, get the booster shot. Scientists continue to work on developing a vaccine that can trigger even better immune protection, especially against new variants.

Testing is also critical for containing this pandemic. Health insurance covers most home self-administered test kits, or they cost very little. Early detection can help you seek treatment early and prevent spread of the virus to your loved ones.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

What we know about the Omicron variant and its latest version

Since the Omicron variant (BA.1) of SARS-COV-2 first emerged in late November 2021, it has now been detected in more than 145 countries worldwide.

Characteristics of the Omicron variant

Based on the data from the World Health Organization, Omicron is highly transmissible and rapidly replacing Delta as the dominant SARS-CoV-2 variant. Omicron has more than 30 genetic mutations of the spike protein. As explained in one of our previous blogs, the SARS-CoV-2 spike protein acts like a gatekeeper, allowing the virus to bind to the ACE-2 receptor, and to enter and infect human cells. In fact, Omicron shows increased capacity to infect the cells, particularly those in the nasopharyngeal area but less so those in the respiratory tract. Thus, close contacts are at a higher risk of becoming secondary cases. This is high likely due to its transmissibility and immune evasion.

The Global Virus Network (GVN) recently published a detailed perspective on Omicron’s transmissibility, immune evasion, and pathogenicity. You can read it here.

Omicron shows more upper respiratory tract infections as compared with Delta and other variants which prefers lower respiratory tract. In addition, although patients with Omicron infection have a lower risk of being hospitalized, the variant continues to overwhelm hospital systems worldwide as the number of people infected grows exponentially.

Vaccines continue to work

According to a recent study in JAMA Network, people administered three doses of mRNA COVID-19 vaccine show higher protection against both Omicron and Delta variants, compared to unvaccinated populations (Omicron odds ratio, 0.33 and Delta odds ratio, 0.065), and recipients of two doses (Omicron odds ratio, 0.34; Delta odds ratio, 0.16). Also, according to U.S. Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report on Jan 21, 2022, during both Delta- and Omicron-predominant periods, a third dose of COVID-19 vaccines (often called a booster) was highly effective in preventing COVID-19-related admissions to intensive care units and overall hospitalizations (94% and 90%, respectively). Booster vaccination can also help reduce the burden on the health care system amid the Omicron wave.

Omicron’s sister – BA.2

Omicron’s sister, subvariant BA.2, was first identified in India and South Africa in late December 2021. BA.2 emerged from a mutation of the Omicron variant. Early observations from India and Denmark suggest no dramatic differences in severity of illness between those infected with the BA.1 and BA.2 strains. Both share 32 mutations but differ by 28 mutations.

As of the last week of January, BA.2 was gaining dominance in India, Denmark, and Sweden and had spread to more than 40 countries. More research is needed to better understand BA.2 but so far nothing indicates any changes in sensitivity to the vaccines. So, meanwhile, please get the COVID-19 vaccines and boosters when eligible.

What is Omicron’s impact on long COVID?

As the virus keeps mutating, the post-acute effects of the COVID-19 virus (known as long COVID) are still largely unknown — especially the impact of the newest variant Omicron. Indeed, some people who were infected by SARS-COV-2 experience persistent symptoms and/or delayed or long-term complications four weeks after initial onset of symptoms. Due to the broad tropism of SARS-COV-2, people experience a wide range of long-lasting health problems.

A study published in The Lancet journal eClinical Medicine, reported responses from 3,762 participants with confirmed or suspected COVID-19 infections from 56 countries. The most frequent symptoms experienced by these COVID patients after six months were fatigue, post-exertional malaise, and cognitive dysfunction, or “brain fog.” In fact, most respondents (>91%) reported persistent symptoms more than 35 weeks after recovery. Furthermore, a recent preprint paper indicates that 65% of the study participants who recovered from COVID-19 during the first wave of the pandemic experienced some olfactory dysfunction (loss of smell) even 18 months later!

Long COVID is potentially a major clinical and public health challenge, and more multidisciplinary research is crucial for its appraisal. Global alliances are needed to investigate the duration and pathology of prolonged COVID-19 in different geographical and environmental contexts, as well as its mechanisms and potential treatments.

Scientists across the world should share clinical samples and data. Defining the contribution of autoimmunity and other host immune responses during long COVID-19 can provide important information. Institutions like USF Health and GVN can take advantage of our current advances in SARS-COV-2 research and support such critical efforts.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

December 8, 2021

Importance of a global, collaborative diagnostic arsenal to detect and fight pandemics

The recent emergence of a new variant of concern, Omicron, has fueled a resurgence of anxiety in a pandemic-weary world. The first officially confirmed Omicron (B.1.1.529) infection was from a sample collected in South Africa on Nov. 9, but some recent studies based on wastewater analyses suggest the Omicron variant was already circulating about two months before then.

This latest variant spread quickly in South Africa and worldwide, including the U.S. (the first known cases in Florida were reported earlier this week.) Due to its rapid transmission and the large number of mutations in its spike proteins, many countries imposed travel bans on southern African countries. Omicron has re-emphasized the importance of accurate, rapid, and massively deployed diagnostics to effectively contain viral transmission.

Amid global spread of the Omicron variant, under the High Patronage of H.S.H. Prince Albert II of Monaco, the Global Virus Network(GVN), the Centre Scientifique de Monaco, the Foundation Prince Albert II de Monaco, the Merieux Foundation, and the Princely Government of Monaco, hosted the GVN & Monaco COVID-19 Diagnostic Conference: Promises and Challenges on Dec. 2 and 3. This conference brought together academia, industry, and government to boost innovative diagnostic technologies for meaningful collaborations with a focus on developing countries. Specific workshops addressed:

Progress in cutting-edge technologies for COVID-19 diagnostics and platforms readily available for the control of the ongoing COVID-19 pandemic and for future pandemic preparedness.
Application of such novel diagnostic systems for implementing global health strategies.
Approaches for sharing resources and technologies, especially with developing countries.

The complete conference presentations are available here.

Testing: Immunology, Saliva and Rapid Testing

In response to emerging pathogens, it is critical to understand the dynamics of viral shedding in different individuals to identify the most vulnerable time for viral transmission, to select efficient diagnostic tests such as molecular and immunology tests; and to prevent super-spreader events.

The development of the neutralizing antibody test has been very useful to understand protective immunity against SARS-CoV-2 in both naturally infected and vaccinated people. This antibody test helps to predict the levels of protection against the virus in the context of waning immunity and breakthrough infections, and to guide public health policy implementation. The presentations from Monaco offered a first proof of concept on how an entire population of vaccinated individuals can be tested for neutralizing antibodies, with the potential to develop personalized management strategies for future boosts.

Saliva samples have become a realistic and beneficial strategy in COVID-19 diagnostics. Saliva-based detection assays can decrease cost and turnaround time. Different assays with different demographic samples have demonstrated usefulness and broad applications. Importantly, saliva may be superior to nasal swabs for early detection of infection.

Rapid tests for COVID-19 can also be useful in developed countries as well as developing countries. Various advanced technologies and platforms (i.e., CRISPR and biosensor-based assays) are now available for sensitive and cost-effective COVID-19 diagnostics. These advanced techniques are adaptable and deployable in the field, offering point-of-care testing and massive throughout.

Value of biomarkers and genomic sequencing

Identification and monitoring of biomarkers in patients offer the potential to predict disease status and severity, identify targets for antiviral drugs, and develop personalized treatments. Advanced genomic sequencing analysis facilitates rapid identification of emerging variants and predominantly circulating variants, leading to implementation of public health measures. The water-waste surveillance approach may also quickly identify such variants and provide valuable information required to protect the community.

With data sharing and database systems for SARS-CoV-2 genome sequencing, we can now track variants of concern and predict the effects of their mutations on the efficacy of existing vaccines, therapeutics, and diagnostics. Specifically, risk assessment algorithms help us track the emerging variants and analyze the functional impact of mutations. Such programs forecast that the Omicron variant could be of particular concern because of many mutations in the virus’s receptor binding domains and their potential impact on how well vaccines and treatments work.

Global health strategy needed

Global collaboration, partnership, and leadership are vital to mitigate the current pandemic and prevent the next. Health organizations, including FIND and Unitaid, are working to break the chains of transmission and facilitate public health interventions by distributing affordable, accountable, and rapid diagnostic kits to developing countries. Yet, lack of testing in these countries (especially, remote areas) greatly hinders disarming the current pandemic. Future pandemic preparedness will rely not only on our access to inexpensive, rapid diagnostics and our genome sequencing capacity, but also on adequate education, training, and regional manufacturing capability with technology transfer. Furthermore, establishing global partnerships to share samples (biobanking) and available database systems can enhance our efforts to rapidly develop the diagnostics needed for infectious diseases.

Robust diagnostics vital for pandemic preparedness

In conclusion, preparing for future pandemics will require new levels of partnerships among academia, industry, and government sharing a global vision. We need comprehensive approaches integrating engineering, medicine, public health, and virology. We need an “Operation Warp Speed” program to accelerate the development, clinical testing, manufacturing, and procurement of novel diagnostic tests. We must merge the best experts worldwide in a science-driven and independent spirit to provide better mitigation strategies. Both GVN and USF Health have ongoing efforts to define the impact of the Omicron variant. We are fluid in our specific research goals as the pandemic continues to evolve.

As Dr. Charles Lockwood, senior vice president for USF Health and dean of the Morsani College of Medicine, wrote in a recent letter to USF Health’s faculty, staff and students: While we wait for more data to be collected about Omicron, “in the interim, the single most effective tool we have to ensure the public’s health, a vibrant economy and our collective sanity is multi-dose COVID-19 vaccination. So, if you haven’t been vaccinated – do it now, and, if you qualify, get your booster shot. In other words, do what USF Health has done so well over the past two years – follow the science, use common sense, and keep calm and carry on.”

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

November 5, 2021

Update: COVID-19 Pandemic and Mental Health

Last month, the Centers for Disease Control and Prevention (CDC) added mental health disorders, such as mood disorders and schizophrenia spectrum disorders, to the underlying medical conditions associated with higher risk for severe COVID-19. Twenty months after the outbreak began, it has once again put mental health in the spotlight.

Pre-existing mental health disorders and COVID-19

Based on data from the World Health Organization, mental health disorders increased 13% globally in the last 10 years. One in five children and adolescents worldwide has a mental health problem.

Early this year, a cohort study published in JAMA Psychiatry found that a schizophrenia spectrum diagnosis was associated with an increased risk of death among 7,348 adults with laboratory-confirmed COVID-19 in the New York Health system. Another study recently published in JAMA Psychiatry showed that people with pre-existing mood disorders are at increased risk of hospitalization and death from COVID-19 and should be classified as a high-risk group based on those pre-existing conditions.

Emerging mental health conditions associated with COVID-19

People commonly experience stress or fear of the uncertain or unknown. The coronavirus pandemic has completely changed our way of life — from working at home, virtual classrooms, outdoor dining, and restricted group gatherings to lack of physical contact and unemployment. Many people reported experiencing one or more mental health conditions. According to research conducted by the CDC between August 2020 and February 2021, 41.5% of adults reported recent symptoms of an anxiety or a depressive disorder. That’s up from 36.4%. The figure was 11% the year before.

A meta-analysis published in Nature reveals a total prevalence of anxiety symptoms of 32.6% during the pandemic. For depression, the prevalence was 27.6%; for insomnia, 30.3%; and for post-traumatic stress disorder symptoms, 16.7%.

Importance of addressing psychological distress

Understanding the pandemic’s influence on mental health is critical so that we can help prevent and treat the mental conditions of those in need. As discussed in a previous blog post, the collective and individual psychological impact can last long after the pandemic ends. The emotional well-being of health professionals and communities at large must be addressed during and after the pandemic. Appropriate measures should be taken to overcome the effects of psychological distress on different target groups.

During this pandemic, we encourage everyone to remain aware of potential psychological responses, maintain a positive attitude, take precautions to protect yourself and others from infection, stay in touch with family members and the community, and take care of your body and mind. Most importantly, seek appropriate help when needed.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

September 29, 2021

Update on COVID-19 breakthrough cases

We first covered COVID-19 breakthrough cases in our July 28, 2021, blog. Here we update what we know about breakthrough infections based on the most recently published statistics.

As of Sept. 20, 2021, the U.S. Centers for Disease Control and Prevention (CDC ) reported 19,136 patients with COVID-19 vaccine breakthrough infections were hospitalized or died. That is less than 0.01% of the 181 million fully vaccinated people in the United States.

Despite an early national vaccination campaign and a very high vaccination rate compared to other countries, Israel’s increasing breakthrough cases last month prompted global concern. All Israelis are enrolled in health maintenance organizations, which makes it easier to track the vaccination data. Israel has so far administered COVID-19 vaccines to nearly 63.9% of the country’s population. Yet, because of the reports on breakthrough cases, some people started questioning the effectiveness of the COVID-19 vaccines.

The worldwide spread of the COVID-19 Delta variant and reports of breakthrough cases have raised questions about vaccine effectiveness.

Vaccines work

In short, vaccines work. Worldwide, most breakthrough cases causing severe disease have occurred in patients who are old or have underlying medical conditions. For example, a group of researchers at Yale University studied 969 individuals who tested positive for COVID-19. According to this comment published in The Lancet Infectious Diseases, 54 out of the 969 individuals (5.6%) admitted to the hospital for confirmed SARS-CoV-2 were considered breakthrough cases. Among all breakthrough cases, 14 (26%) out of the 54 patients experienced severe or critical illness. The median age for the 14 patients was 80.5 years, and they all had pre-existing comorbidities.

No vaccine is 100% effective. However, the COVID-19 vaccines are very effective against severe illness and hospitalization. The table below shows the efficacy of the main vaccines currently available to protect against variants of concern. For more information, please visit the Global Virus Network Variants and Vaccines Resource Portal.

Table – Vaccine efficacy against variants

Another study published in The Lancet Infectious Diseases estimates the number of SARS-CoV-2 infections and COVID-19-related hospitalizations and deaths averted by the nationwide vaccination campaign in Israel. This study estimated 116,000 (73.1%) SARS-CoV-2 infections, 19,467 (79.1%) COVID-19-related hospitalizations, and 4,351 (79%) deaths were averted by Israel’s fully vaccinated population. Without the national vaccination campaign, Israel probably would have experienced triple the number of hospitalizations and deaths compared to what actually occurred during its largest wave of the pandemic to date. A surge of that magnitude may well have overwhelmed the country’s health care system.

Who should get a booster shot?

On Sept. 22, the U.S. Food & Drug Administration authorized a booster dose of the Pfizer-BioNTech COVID-19 vaccine for certain populations. Many countries are still debating the necessity of the booster shot. Israel has also been at the forefront of distributing a booster shot.

An article published in The New England Journal of Medicine found that the rates of confirmed COVID-19 and severe illness were substantially lower among adults age 60 or older who received a booster dose of the Pfizer vaccine at least 5 months after receiving their second dose of the mRNA vaccine. We believe that the booster shot is needed by the elderly and fragile. Others should wait patiently for results of ongoing worldwide studies examining the duration of protection.

Studies indicate that being fully vaccinated is the best protection against hospitalization and death from COVID-19, including from the Delta viral variant.

Get Vaccinated

Meanwhile, if you’re not already vaccinated, please get vaccinated to protect yourself and your loved ones. Only 2.2% people in low-income countries have received one dose of the vaccine. Vaccine equality is needed globally to end this pandemic, because spread of the COVID-19 virus does not stop at borders.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

August 25, 2021

Back to School: Children and COVID-19

This week, the U.S. Food and Drug Administration fully approved the Pfizer’s COVID-19 vaccine. We really hope this will greatly increase confidence in the vaccine, leading to much higher vaccination rates. Meanwhile, as more children head back to school for in-person learning, the issue of when vaccines might be available for students under age 12 has become an increasingly hot topic.

Many schools are reopening for in-person learning as the highly contagious Delta variant continues to circulate widely, placing students at increased risk of contracting the COVID-19 virus.

Update on cases in children

Children younger than 12 are not yet eligible to be vaccinated. However, most U.S. schools open in August or just after Labor Day and many of these younger students are at increased risk of contracting SARS-CoV-2 due to ongoing worldwide spread of the highly contagious Delta variant. As of August 19, more than 4.59 million children had tested positive for COVID-19 , according to the data from the American Academy of Pediatrics. They represented 14.6% of total cumulative cases. In fact, they accounted for 22.4 percent of the weekly COVID-19 cases reported last week, with an increasing number of children hospitalized. Although they are still much less likely than adults to develop severe illness, children might spread the virus. On the other hand, as discussed in a previous blog post, very few children develop a rare systemic inflammatory response called multisystem inflammatory syndrome in children (MIS-C).

Prevention strategies to protect children

Vaccine clinical trials are still underway for children ages 6 months to 11. Without a vaccine, other intervention strategies such as mask wearing and physical distancing become even more important to keep children healthy. The Centers for Disease Control and Prevention (CDC) recently updated its guidance for COVID-19 prevention in K-12 schools. The agency recommends universal indoor masking for all students (age 2 and older), staff, teachers, and visitors to K-12 schools, regardless of vaccination status. Outside school, parents should help minimize a child’s contact with others to reduce the chance of transmitting the virus. Limiting outdoor play time with other children is strongly recommended. In previous blog posts, we have repeatedly highlighted the importance of screening, testing, contact tracing and hand washing to contain the outbreak. Schools should implement comprehensive prevention strategies to protect students, staff, and the community.

While children age 12 and older are eligible for the vaccine, the percentage of fully vaccinated children so far remains low. Only 43 percent of 16-to 17-year-olds and 33 percent of 12-to 15-year-olds are fully vaccinated, according to a newly released report from the American Academy of Pediatrics. We strongly recommend that parents or guardians consider vaccinating eligible children against COVID-19. It is a critical tool to help protect both your children and the people around them. To learn more about COVID-19 vaccines for children and teens, please visit the CDC site.

The percentage of children age 12 and older fully vaccinated against COVID-19 remains low.

Reliable sources of information needed

As the pandemic continues evolving, there is a lot of misleading information about COVID-19 vaccines and variants. The Global Virus Network (GVN) recently published a detailed scientific perspective about the COVID-19 vaccines and variants. Read it here. Earlier this year, GVN also launched a comprehensive resource portal, which is updated daily with the latest scientific answers to your questions about COVID-19 variants and vaccines.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

July 28, 2021

Putting vaccine breakthrough COVID in perspective

To date, more than 195 million people worldwide had been infected by SARS-CoV-2 and more than 4 million of them have lost their lives. In fact, some studies suggest that the numbers might be much higher, close to twice these figures. Thus, as the COVID-19 pandemic continues to disrupt our daily lives, the importance of vaccinations will only grow. Meanwhile, more attention is turning to COVID-19 breakthrough cases.

What is a breakthrough case?

COVID-19 breakthrough means that some people may still become infected with SARS-CoV-2 despite being fully vaccinated. That sounds alarming. But, breakthrough cases are rare. Importantly, most breakthrough cases will not cause severe illness, hospitalization or death.

On May 1, 2021, the U.S. Centers for Disease Control and Prevention (CDC) transitioned from monitoring all reported COVID-19 vaccine breakthrough cases to focus on identifying and investigating only breakthrough case hospitalizations or deaths from any cause, including causes not related to COVID-19. As of April 30, 2021, over 10,000 breakthrough infections were reported in the U.S.

Meanwhile, according to the CDC, more than 161 million people, or 48.8% of the total U.S. population had been fully vaccinated against COVID-19 as of July 19, 2021. That means breakthrough with clinical symptoms only occurred in about 1 of every 16,100 persons vaccinated. Moreover, only a very small percentage (<0.003%) of such patients were hospitalized or died from COVID-19 vaccine breakthrough infections, with 5,914 cases reported.

Why does breakthrough infection happen?

The vaccine clearly works; however, no vaccine is 100% effective. The point here is not to produce a 100% effective vaccine, but to get more people to receive the currently available COVID-19 vaccines. The more people are vaccinated, the faster the outbreak will be contained.

In addition, as the current pandemic keeps evolving, continued circulation of the virus leads to the emergence of new SARS-CoV-2 variants. Yet, a major benefit of the current vaccines is their efficacy against both the original SARS-CoV-2 strain and the major circulating variants – including the latest variants.

For example, an article published in The New England Journal of Medicine reports two doses of the Pfizer-BioNtech mRNA vaccine (full vaccination) provides 88% protection against the Delta variant. The Delta variant was first detected in India in December 2020 and has spread to more than 80 countries, quickly becoming the most frequently reported variant in many countries. Also the two-dose Pfizer-BioNtech vaccine regimen was shown to be 94% effective against the Alpha variant (previously called the “UK” variant). Two doses of the Oxford-AstraZeneca vaccine (full vaccination) were 67% effective among people with the Delta variant and 75% effective in those with the Alpha variant.

Why study breakthrough cases?

Although we don’t need to overact to breakthrough cases, we can benefit by learning more about them. For instance, it would help to understand whether certain COVID-19 vaccines might work better than others in protecting against some dominant viral mutations. Sometimes, vaccines must be modified to fight specific variants. Studying breakthrough cases will give us a clearer picture of the current pandemic and help scientists decide if and when booster shots are needed.

Get the vaccine

The Public Health England confirmed that two doses of the Pfizer-BioNtech vaccine are 96% effective against hospitalization for infections caused by the Delta variant. Conversely, an analysis of government data by the Associated Press showed that nearly all COVID-19 deaths in the U.S. were in unvaccinated people. As mentioned before, vaccines also greatly prevent severe illness and hospitalization. COVID-19 vaccines are widely accessible in the U.S., so please get yours as soon as you can to protect yourself and loved ones.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

June 14, 2021

What do we know about the Delta variant?

On May 31, the World Health Organization (WHO) announced a simpler naming system that identifies SARS-CoV-2 so-called variants of interest (VOI) and variants of concern (VOC) by giving each variant a name from the Greek alphabet. The Delta variant, aka B.1.617.2, spreading globally including in the U.S., has attracted the most attention in recent weeks.

The World Health Organization (WHO) has begun naming SARS-CoV-2 variants of concern and interest after letters of the Greek alphabet.

Variants of interest vs. variants of concern

Before delving into the Delta variant, we need to understand the definitions of VOC and VOI. VOC are defined as variants that clearly show one or more of the following changes: increased transmissibility, enhanced disease severity, or decreased vaccine protection. The Alpha variant (B. 1.1.7) first documented in the United Kingdom in September 2020 was the first SARS-CoV-2 variant of concern. At least 80% of COVID-19 cases in the UK over the past months were caused by the Alpha variant.

VOI encompasses variants predicted to significantly impact virus transmissibility, disease severity and/or the effectiveness of vaccines, diagnostics, or treatments. However, the evidence is preliminary and warrants further studies.

The WHO definitions of VOI and VOC, which we refer to in this blog, may vary somewhat for each country since the variants differ by regions. For example, the Epsilon variant, B.1.427, first documented in California is defined as a VOC by the Centers for Disease Control and Prevention (CDC) and a VOI by WHO.

Why is the Delta variant so concerning?

The Delta variant, first detected in India in October 2020, quickly led to a surge in cases in India, where younger people are getting sick more frequently. It quickly spread to the United Kingdom and more than 60 countries. Now, the Delta variant is increasingly replacing the Alpha variant and contributes to 75% of cases in the UK. This variant has begun spreading in other European countries and accounts for 6% of new coronavirus infections in the United States.

The Delta variant, first detected October 2020 in India, is considered 40% to 50% more transmissible than the Alpha variant. It has spread to more than 60 countries, including the U.S.

Transmissibility

The Delta variant is considered 40% to 50% more transmissible than the Alpha variant. Several mutations in the Delta variant may affect the receptor binding protein (452 and 478) and induce a deletion of a portion of the N-terminal domain; these changes may account for the rapid global spread of this variant.

Disease severity

No solid evidence suggests that the Delta variant induces a more severe disease. Keep in mind that the clinical effect of a given SARS-CoV-2 variant depends on both its intrinsic properties and many epidemiological parameters. The same concern arose earlier about the Alpha variant, which does not induce a more severe disease even though the variant is now recognized as more contagious than previous isolates. Thus, exercise caution when interpreting the handful of recent studies in the UK and India suggesting that the Delta variant induces increased hospitalization rates and COVID-19 severity.

The AstraZeneca COVID-19 vaccine appears to be less effective against the Delta variant. | Giovani Cancemi-stock.adobe.com

Vaccine efficacy

Although in vitro neutralization is less effective against the Delta variant, a recent study in humans shows only a slight difference in vaccine effectiveness against the Delta variant compared to the Alpha variant after completing two doses of Pfizer vaccine. The Pfizer vaccine was only 33% effective in preventing COVID-19 after one dose, but as much as 88% after two doses.

Unfortunately, the Oxford-AstraZeneca vaccine appears less effective against the Delta variant, and this may contribute to the ongoing new surge of COVID-19 in the UK despite massive vaccination of the population. Interestingly, the rates of hospitalization and deaths in the UK have not significantly increased. So, while the AstraZeneca vaccine may not fully protect against circulation of the virus, it does appear to protect against severe COVID-19.

It is good news that the Pfizer vaccine we are using in the U.S works well against this variant, but individuals must complete the two doses to be adequately protected. Also, the story of the Delta variant is a warning. The COVID-19 pandemic is not over, so all eligible people should get fully vaccinated as quickly as possible to protect themselves and others.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

May 13, 2021

COVID-19 vaccines for children begin

This week, the U.S. Food and Drug Administration (FDA) authorized Pfizer’s COVID-19 vaccine for adolescents ages 12 to 15 under the agency’s expanded emergency use authorization (EUA). Many consider this an important step toward controlling circulation of the virus and eventually ending the pandemic. However, some parents have mixed views about vaccinating their children against COVID-19. What do parents or guardians need to know?

Pfizer’s COVID-19 vaccine for adolescents ages 12 to 15 has been authorized under an expansion of the FDA’s emergency use authorization.

COVID-19 cases in children

As of last week, over 3.85 million children tested positive for COVID-19 since the pandemic began, according to the most recent report issued by the American Academy of Pediatrics. Children account for 14% of all cases in the United States. During the week of April 29 to May 6, 2021, children represented 24% of the new weekly cases. Most children with COVID-19 have mild symptoms or no symptoms at all. But whether they are mildly ill or asymptomatic, they (like adults) can still spread the virus to others. The Global Virus Network recently published a detailed scientific perspective regarding the SARS-COV-2 transmission to, from, and among children. Read it here.

Very few children develop an extremely rare but significant systemic inflammatory response 4 to 6 weeks after acute SARS-CoV-2 infection. Although the disease-causing mechanisms of multisystem inflammatory syndrome in children (MIS-C) are not well understood, the Centers for Disease Control and Prevention notes that the infection can cause inflammation of several organs, including the heart, lungs, kidneys, brain, skin, eyes, stomach and intestine. Most MIS-C infections resolve with treatment.

The aim of vaccinating children is not to prevent severe COVID-19, which is an exceptional event in children. Rather, vaccination of this young population is meant to further prevent circulation of the virus and protect the health of the broader community. Fewer overall infections in the population at large, including children, mean that vaccine or treatment-resistant variants have less of a chance to become prevalent.

Vaccine pros and cons

In late March, Pfizer announced that in its Phase 3 trial in children, the COVID-19 vaccine demonstrated 100% efficacy and robust antibody responses. This U.S. study was conducted among 2,260 children ages 12 to 15. Half of the study participants received a placebo; 18 children in the placebo group were diagnosed with COVID-19, compared to none in the vaccinated group. The Pfizer COVID-19 vaccine dose for children ages 12 to 15 is the same as that given to adults. Children should also receive two doses at least 21 days apart.

Based on the randomized, placebo-controlled clinical trial, common side effects include pain at the injection site, tiredness, headache, chills, muscle pain, fever, and joint pain. Most side effects were reported after receiving the second dose. This is consistent with reported side effects in people ages 16 and older. According to the FDA press release, the EUA in younger adolescents is supported by the immunogenicity and an analysis of COVID-19 cases. In this analysis, immune responses among study participants ages 12 to 15 were as good as those exhibited by people ages 16 to 25.

However, it is unclear how long protection from the vaccine will last. Also, we know that children with a known history of severe allergic reactions should not receive the vaccine. Meanwhile, Pfizer is conducting a phase 1/2/3 seamless COVID-19 vaccine study in children ages 6 months to 11.

Overall, given these very encouraging results, we urge parents or guardians to consider vaccinating eligible children against COVID-19 now that schools, restaurants, sporting events, and other venues are reopening.

Authorizing vaccinations for younger populations represents another important step forward in reducing the public health burden caused by the COVID-19 pandemic. At the same time, keep in mind that unless vaccines are exported to low-income countries, the massive vaccination efforts underway in richer countries will not end this pandemic’s global reach. As renowned chemist and microbiologist Louis Pasteur used to say: “Viruses do not know borders.”

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

April 21, 2021

Neurological complications of COVID-19

In last blog, we discussed the COVID-19 “long haulers.” The common symptoms of long COVID are neurological.

More than 36% of COVID-19 patients developed neurological symptoms, according to a Chinese study published in JAMA Neurology. Among severely infected patients, the number is even higher (45.5%). More than 80% of hospitalized patients may experience neurological symptoms at some point in the course of the disease. Reported neurological complications include, but are not limited to: stroke, seizure, sleep disorders, encephalopathy, acute cerebrovascular events, impaired consciousness, and encephalitis. Other respiratory viruses, including other coronaviruses such as SARS-CoV-1 and Middle East respiratory syndrome (MERS), exhibit similar neurological manifestations.

Why are neurological complications more common?

In short, we do not know yet. One perspective published in Nature Reviews Neurology suggests that neurological complications may be caused by the direct effects of the virus as well as the systemic response to infection. In particular, the complications appear to encompass three distinct categories:

Neurological consequences of pulmonary and related systemic diseases, such as stroke
Symptoms caused by the direct invasion of the virus into the central nervous system, such as encephalitis.
Neurological abnormalities related to immune-mediated complications after infection, such as Guillain-Barré Syndrome (GBS).

One hypothesis proposes that many neurological symptoms of COVID-19 may be triggered by an exaggerated immune response to the viral infection, rather than a direct infection of the brain or nervous system by the virus. But scientists are still learning how the virus affects the brain and other organs over the long haul.

An editorial published this month in the Lancet Neurology highlighted the importance of continuing to study long-term neurological symptoms of COVID-19. The National Institutes of Health recently launched a database, called the COVID-19 Neuro Databank/Biobank (NeuroCOVID), to track neurological symptoms associated with COVID-19. As the pandemic continues to evolve, further studies are needed to better understand the full spectrum of neurological symptoms to improve patient diagnosis and treatment.

Most neurological symptoms are observed in or reported by adults. Even though children rarely suffer severe illness from COVID-19 infection, those who do are at risk of developing neurological symptoms, such as seizures and encephalopathy.

We need to investigate the role of autoimmune responses and other changes that cause a range of lingering symptoms in some people after initial recovery. The Global Virus Network recently published a detailed scientific perspective regarding COVID-19 and autoimmunity. You can find it here.

COVID-19 vaccines and risk of neurological complications

As of April 21, more than 928 million COVID-19 vaccine doses had been administered globally. Based on the data from Centers for Disease Control and Prevention (CDC), nearly 216 million had been administered in the U.S. Concerns about neurological complications caused by coronavirus have risen as the vaccine has become more widely available.

Dizziness, headache, muscle pain, and paresthesia (a burning, tingling skin sensation) are common side effects of the vaccines. According to a detailed report by the CDC, no reliable data exists to suggest that any COVID-19 vaccine is associated with a higher risk of neurological disease. Overall, the benefits of COVID vaccination far outweigh the risks of developing neurological complications. So, please heed the recommendation of public health officials: To protect yourself and others, get vaccinated as soon as you are eligible.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

April 1, 2021

Searching for answers to help COVID-19 ‘long haulers’

As the COVID-19 vaccine rollout continues in many countries around the globe, the long-term health consequences of the pandemic are drawing more attention.

What is long COVID?

While most people recover from COVID-19 and resume their normal lives after about two to three weeks, some continue to suffer from symptoms after their initial recovery. This emerging condition is referred to as “long COVID,” and individuals with the lingering illness are known as “long haulers.” Evidence now suggests that tens of thousands of people suffer from persistent, sometimes debilitating COVID-19 symptoms after apparent resolution of the disease.

In one prospective, single-center study, reported in JAMA Network Open, nearly one-third of COVID-19 patients, including healthy younger people, had several persistent symptoms six months after infection onset.

What are the lingering symptoms?

According to the Centers for Disease Control and Prevention, the most commonly reported long-term symptoms of COVID-19 include fatigue, shortness of breath, cough, joint pain, chest pain, brain fog, and even neurological complications. A negative COVID-19 test does not mean the patient has fully recovered from clinical symptoms.

A study in China, published in The Lancet, suggests that as many as 76% of COVID-19 patients experienced at least one long-term symptom 6 months after an acute infection; fatigue, muscle weakness and difficulty sleeping were the main symptoms experienced. Other reports suggest that long COVID-19 associated with several symptoms may affect as many as 30% of infected patients. The risk of anxiety or depression also need to be considered, especially for patients with more severe COVID-19.

The truth is that we do not know the exact prevalence of long COVID, because the interpretation of some symptoms is difficult. Yet, clearly, how the virus affects long-term health and quality of life is a real problem.

Underlying reasons

Many studies are underway to investigate why people develop long COVID. According to a study published in the Nature Medicine, elderly, female, and overweight patients and those who show a certain pattern of symptoms in the first week of illness are expected to develop long COVID-19. Long COVID afflicts not only older people or those with underlying health conditions, but also healthy young people, some of whom were asymptomatic when initially infected.

Management of long COVID

Because COVID-19 is a new virus and no standard practice is yet established, the diagnosis of long COVID remains challenging. The National Institute for Health and Care Excellence in the United Kingdom recently published a guideline for managing long COVID. It is critical for doctors to take patient perspectives into consideration when making a diagnosis. Meanwhile, post-recovery follow-ups are critical for long haulers. Nurses, rehabilitation specialists, mental health professionals and community support are needed to promote full recovery from long COVID.

More research needed to guide care

Many questions remain unanswered. Can the COVID-19 vaccine help prevent or reduce prolonged symptoms? Why are certain people more susceptible to long COVID? What is the underlying cause of these persistent symptoms? Longer follow-up studies in larger populations are needed to understand the long-term symptoms and full health consequences of COVID-19.

The good news is that many institutions, funding agencies and researchers are already focused on this important area of research. The World Health Organization works with its Global Technical Network for Clinical Management of COVID-19, researchers and patient groups around the world to design and carry out studies to better understand long COIVD. The scientific findings will be used to further guide patient care. The National Institutes of Health recently launched a large new initiative to study long COVID.

Several funding opportunities aim to learn more about how SARS-CoV-2 may lead to widespread and lasting symptoms, and to develop ways to treat or prevent the long-term effects of infection. Meanwhile, we must all continue to practice public health measures that work – wear masks, maintain physical distance and wash our hands. When it is your turn, please get vaccinated to stop the spread of the virus and protect yourself and others.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

March 10, 2021

COVID-19 variants and vaccines: An uphill battle

It has been 15 months since the first COVD-19 case was reported and nearly a year since we launched this blog. COVID-19 remains the hottest topic in the world. In particular, the impact of SARS-CoV-2 variants on contagiousness, the severity of COVID-19, and vaccine effectiveness presents a major challenge for alleviating the SARS-CoV-2 pandemic.

Variants dominating the spread of SARS-CoV-2

Three most worrying variants of COVID-19 so far dominate the current spread of the SARS-CoV-2 virus: B 1.1.7 (United Kingdom), B1.351 (South Africa), and P1, AKA B1.1.28 (Brazil). You can refer to our Jan. 20, 2021 blog and the Global Virus Network resource portal (see below) for details.

The situation has become increasingly complex as several other variants emerge. For example, Cal. 20.C, AKA, B1429 was first discovered in California in July 2020 and now accounts for nearly half of COVID-19 cases in Southern California. The biological characteristics of this new variant are still unknown, so it is unclear whether this variant’s surge is because of its intrinsic contagiousness. Moreover, B.1.1526 was recently identified in New York and a first study shows that patients infected by this novel variant are on average older and hospitalized more often.

So, what does this mean? It is normal for a virus, in particular an RNA virus like COVID-19, to mutate and we will continue to see the emergence of other mutants. These mutations are favored by combining high rates of virus circulation and selection pressure through the antibodies against the virus. Antibodies are generated after either natural infection or vaccination. The increasing degree of immunity in the population conferred by these antibodies increases “selection pressure” on the virus; that is, it favors COVID-19 variants that can partially escape the body’s immune defenses. Only massive and rapid vaccination can stop the virus from circulating without imposing a selection pressure.

Graphic courtesy of the Global Virus Network

How much do variants impact COVID-19 vaccines?

The short answer is not significantly, so far. All the current vaccines demonstrate efficacy against the initial SARS-CoV-2 strain and the major circulating variant: the B.1.1.7 (U.K.). Moreover, they are efficient at averting transmission of the virus as well preventing symptomatic and severe COVID-19. This is good news; however, we must press forward to meet the major challenge of massive and rapid vaccination to prevent new, and potentially more dangerous, variants from taking hold.

Many investigations continue. The major concern comes from the B.1.351 (South Africa) and P1- B.1.1.248 (Brazil) variants. Indeed, laboratory tests show that current vaccine-generated antibodies have a reduced capacity to neutralize these two COVID-19 variants. Consistent with these results, clinical studies have shown differences in vaccine efficacy based on the vaccine manufacturer and the variant: 86% U.K. and 60% South Africa with the Novavax vaccine, The Johnson & Johnson vaccine was 72% protective in the U.S. and 58% in South Africa, where the B.1.351 is circulating. This February, a preprint paper reported that the AstraZeneca vaccine is 74% effective against the UK variant versus 84% against the nonvariant strain. In addition, a new study from the University of Oxford indicates that AstraZeneca’s vaccine is effective against the B1.1.28 (Brazil) variant, but detailed information has not yet been publicly released.

Despite their lower efficacy against the South African variant, the current vaccines still protect against severe COVID-19 and this is a very important. Nevertheless some companies, such as Moderna, have already initiated the design of novel booster vaccines intended to specifically protect against some variants, including the one from South Africa.

Finally, a recent trend could prove very beneficial to vaccination. The emerging variants appear to display the same mutational patterns. That means the virus might, in fact, have a limited number of possibilities to escape the immune response. If confirmed, this would have a major impact.

Updates, clear guidelines more important than ever

As the virus continues to spread worldwide and vaccine implementation advances in many countries, it is critical to bring all available information about COVID-19 variants and vaccines together and to convey clear guidelines to the general public and the scientific community. Furthermore, we must update the public about the swift and continuous evolution of SARS-CoV-2. In response to this urgency, GVN recently launched the GVN COVID-19 Variants and Vaccines Resource Portal hosted on the GVN website (click graphic below to access). The website provides the latest scientific answers to important questions about the spread of emerging variants, vaccine development and vaccination policies to both the public and the scientific community.

Coincidentally, USF Health was officially named as the GVN Southeast U.S. Regional Headquarters last month. USF Health is the first regional headquarters named by GVN to provide organizational and leadership support to GVN’s Global Headquarters in Baltimore, Md. In that capacity, USF Health will help strengthen GVN’s initial research response to emerging and re-emerging infectious diseases, such as COVID-19, and its collaborative efforts to plan for, and defend against, future epidemics and pandemics.

The GVN COVID-19 Variants and Vaccines Resource Portal is fully consistent with GVN’s mission and the mission of USF Health, the new GVN Southeast U.S Regional Headquarters. As Dr. Charles J. Lockwood, senior vice president of USF Health and dean of the Morsani College of Medicine, has said: “Together we can, and we must, be better prepared to meet the challenges of the next emerging virus.”

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

January 20, 2021

What do we know about emerging SARS-CoV-2 variants?

Less than a month into 2021 we already face a great challenge with the rapid evolution of SARS-CoV-2 variants and the difficulties of implementing mass vaccinations. Several new SARS-CoV-2 variants have been reported to the World Health Organization: the B.1.1.7 variant in the United Kingdom; 501Y.V2, a.k.a B.1.351, in South Africa; and B.1.1. 248 in Brazil and Japan. What have we learned about these variants, and what are the practical implications for COVID-19 testing, treatments and vaccines?

Epidemiology

Infectivity. First, SARS-CoV-2 is an RNA virus and mutations occur naturally as the virus replicates. Although the overall rate of mutation for SARS-Co-2 is not very high (much less than for influenza), many mutations have been identified in SARS-CoV-2 samples. Most mutations make no significant differences to the virus. Yet, sometimes a mutation makes the virus more contagious and it becomes the dominant strain. For example, the D614G substitution in the gene encoding the SARS-CoV-2 spike protein, which happened as early as February 2020, disseminated worldwide. Thus, monitoring various viral strain sequences is critical to understanding the spread and mutation of the virus.

Based on available preliminary data, the UK’s B117 strain exhibits a surprisingly larger than usual number of viral genetic changes (mutations) — 17 in total. N501Y is one of its worrisome mutations. Indeed, a recent report published in Science suggested that N501Y, located in the receptor binding domain of the SARS-CoV-2 spike protein, increases the protein’s binding affinity to the ACE2 receptor. In other words, the virus becomes more contagious because it more easily attaches to ACE2 and enters human cells. This may explain why the B117 strain spread so rapidly spread throughout the UK. In fact, this strain has now infected most of UK’s population, replacing previous strains and imposing a severe lockdown since November 2020.

A recent preprint indicated that the 501Y.V2 mutation in viral strains identified in South Africa might be 1.5 times as transmissible as previously circulating variants. So far both new variants, (in the UK and South Africa) have spread to more than 50 countries. Some reported patients did not travel recently, indicating that these strains have already initiated community-based (people-to-people) transmission.

Reinfections. Certain SARS-CoV-2 mutations might help the virus evade immune responses triggered by a past infection or vaccination. This is not unusual. For example, the vaccine against influenza must specifically be adjusted to new strains each year. SARS-CoV-2 shows a much lower rate of mutations than influenza. Yet, in a recent preprint, scientists suggested that another mutation, E484K, identified in the B.1.1.28 variant in Brazil and Japan, might reduce the ability of antibodies to SARS-CoV-2 to bind tightly to the spike protein. This may interfere with the effectiveness of antibodies, generated during a previous COVID-19 infection or through vaccination, to neutralize the virus. Brazil reported that a patient initially infected by a usual SARS-CoV-2 lineage B.1.133 was reinfected by this B.1.1.28 strain, which contains mutation E484K in the spike protein. However, let’s be clear: overall, reinfections remain rare.

Disease Severity. No evidence so far suggests that any of the emerging three variants first identified in the UK, South Africa and Brazil cause more severe disease. Most mutated viruses with increased transmissibility generally do not show increased severity and, in fact, may cause milder illness. For example, the D614G mutation referenced earlier caused the virus to spread worldwide, but it has not created more serious symptoms. Finally, animal studies support these observations.

Treatments

Will such variants affect the virus’s response to available COVID-19 treatments? No evidence so far exists for this, but SARS-CoV2 variants may impact the effectiveness of monoclonal antibodies-based treatments. In our Aug. 26, 2020 blog, we explained how neutralizing antibodies (nAbs) work against COVID-19. NAbs prevent COVID-19 viruses from entering human cells to launch infection by binding to the cell surfaces. The most relevant concern is whether mutations will interfere with the neutralizing effects of the antibodies.

Diagnostics

Molecular tests were designed to detect multiple sequences within the SARS-CoV-2 RNA. Thus, diagnostic results are less likely to be affected by one or a few mutations. Yet, both the FDA and certain companies have started to address genetic variants of SARS-COV-2 and specific PCR-based assays are being developed. While viral genome sequencing remains the most accurate detection method, this type of test cannot be performed routinely.

Vaccines

Will SARS-COV-2 mutations impact our capacity to curb the pandemic through vaccines? Overall, the ongoing vaccines are safe and highly effective. In fact, vaccinating quickly and on a larger scale is the best way to contain mutants, because this approach rapidly curbs circulation of the virus that would otherwise generate new variants. A recent preprint published by one of the Global Virus Network center directors, Dr. Scott Weaver of the University of Texas Medical Branch at Galveston, indicates that sera of 20 participants in a trial of the mRNA-based Pfizer–BioNTech COVID-19 vaccine efficiently neutralized the virus despite the N501Y mutation. On the other hand, we are still concerned about the potential impact of the E484 mutation referenced earlier. So, more comprehensive studies are needed to better understand the impact of mutations on the current COVID-19 vaccines and future vaccine candidates, and vice versa.

Meanwhile, it’s important to continue practicing public health measures – wear masks, maintain physical distance and wash your hands. When it is your turn, please get vaccinated to protect yourself and others around you.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

December 9, 2020

COVID-19 susceptibility and severity: Role of host factors and genetics

We still do not fully understand why certain people with COVID-19 are asymptomatic or experience only mild symptoms. What differentiates those who fight off the SARS-CoV-2 infection without any treatments from others who suffer severe symptoms, and even die from the disease?

So far, we know that underlying health conditions (obesity, diabetes, heart disease, and lung problems to name a few), gender (men are more at risk than women) and age (over 65) increases vulnerability to COVID-19. But, what about genetic make-up? When exposed to the virus, are some people at higher risk of infection and developing symptoms that are more serious simply because they carry or lack one or several specific genes? This question can be posed for each infectious disease, not just COVID-19. Yet, given the huge prevalence of COVID-19, rigorously pursuing the answer could have a major impact on human health.

Why do so many COVID-19 patients exhibit neurological disorders?

In one of our previous blogs, we explained that proteins called spikes protrude from the surface of SARS-CoV-2 particles. This spike protein (S protein) has two subunits, S1 and S2. S1 contains the receptor-binding domain (RBD), which binds to the angiotensin-converting enzyme 2 (ACE2) receptors on human host cells. The S protein conveys the virus to receptors on the host cell surface, helping the virus efficiently invade the human cell to produce more viruses.

However, reports published in Science last month suggest that the differences observed in various tissues infected with COVID-19 may be related to another host factors. The research shows that the membrane protein neuropilin-1 (NRP1), which promotes SARS-CoV-2 entry, is another host factor for the coronavirus infection. Moreover, pathological analysis of olfactory epithelium cells obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells. Within the olfactory epithelium, NRP1 was also observed in cells positive for oligodendrocyte transcription factor 2, which is mostly expressed by olfactory neuronal progenitors. That means the SARS-CoV-2 virus not only enters pulmonary and pharyngeal epithelium but also directly infects the brain, particularly through the nasal cavity, thus better explaining why so many infected patients suffer from neurological disorders, including loss of smell (anosmia) and taste (ageusia). Moreover, understanding the role of NRP1 gene expression in SARS-CoV-2 infection may provide potential targets for future antiviral treatments.

What about the influence of genetics in immune response?

The highly complex human immune response involves many genes. Scientists look for links between specific genetic markers and risk for and severity of disease. Investigating the interplay between human genetics and COVID-19, a study published in the New England Journal of Medicine identified a gene cluster called 3p21.31 on chromosome 3 as a risk locus for respiratory failure after infection with SARS-CoV-2. A study by Regeneron scientists also emphasized the positive link between the 3p21.31 locus and the severity of COVID-19. Another striking paper published in Nature demonstrated that this modified gene cluster is inherited from Neanderthals and carried by about 50% of people in south Asia and about 16% in Europe. In theory, the absence of this particular gene cluster in Africa might in part account for the decreased severity of COVID-19 cases across the continent. Of course, COVID-19 severity depends on many factors, but it is interesting that some genetic variations may also influence the characteristics of the current pandemic.

In a paper published in Science, researchers studied type I Interferons (IFNs)-based immunity, investigating whether defects in this immune defense might account for life-threatening COVID-19. The scientists found that indeed those individuals who lack functional IFNs signaling are more susceptible to severe COVID-19.

In fact, they identified two mechanisms that jeopardize IFNs functioning. First, 3.5 % of patients with life-threatening COVID-19 pneumonia had genetic defects in the genes controlling the type I interferon pathway. Secondly, and this is the first report in virology of this kind, at least 10.5% with severe COVID-19 pneumonia yielded type I interferon autoantibodies that existed before the infection. Autoantibodies are misguided antibodies that attack the immune system instead of the virus. Researchers did not find those autoantibodies in patients who were asymptomatic or experienced milder infections, or in healthy people. Patients with either modified genes or autoantibodies lacked an effective type I interferon-dependent immune response. These findings further underscore the importance of investigating in-depth the interferon pathway to help identify individuals at higher risk for severe SARS-CoV-2 infections.

In summary, the susceptibility to and severity of any infection is the result of interactions between viral- and host-related factors. Therefore, studying human genomics can help us understand the transmission, pathogenesis, susceptibility and severity of the infectious disease, as well as potentially lead to new, advanced COVID-19 diagnostics and treatments. Such studies must be evidence-based and conducted with caution to avoid misunderstandings and stigmatization of groups of patients.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

November 18, 2020

The COVID-19 vaccine race: Are we close to the finish line?

Within the last 9 days, the world has welcomed promising vaccine news from two biotechnology companies, Pfizer in partnership with BioNTech and Moderna. These companies announced that their mRNA-based vaccines offer 90% and 94.4% protection against COVID-19, respectively. Pfizer with German biotechnology firm BioNTech was first to announce the interim analysis of their 44,000-person, phase III trial. Moderna‘s result is based on 95 COVID-19 confirmed cases, 90 of which were in the placebo group. Moreover, in Moderna’s study, all 11 severe COVID-19 infections occurred in patients who did not receive the vaccine. Importantly, both announcements were based on the evaluation of the phase III results by independent scientific committees.

Concurrently, the Gamaleya National Center of Epidemiology and Microbiology in Moscow, Russia, announced interim data analysis of their phase III clinical trial for the Sputnik V COVID-19 vaccine. The center reported that this vaccine, based on an adenoviral vector, demonstrated 92% effectiveness. Despite the undebatable quality of the Russian scientists, it bears noting that these data were based on very few (20) confirmed COVID-19 cases in the vaccinated and placebo groups.

Earlier this month, both Pfizer-BioNTech and Moderna announced late-stage clinical trial data showing that their mRNA vaccines against COVID-19 were highly effective.

What do the interim vaccine results mean?

It means – and this is great news – that different vaccine technologies can produce very significant protection against COVID-19. Last spring, few would have expected to achieve such results in less than a year. Developing a new vaccine generally takes several years. This scientific feat reflects major involvement by academic and industrial partners across the board and substantial funding support from the government. The Global Virus Network has contributed to the massive effort and USF has been at the forefront of the fight.

Yet caution is warranted, because several questions still need to be answered. How long will the vaccine protection last? We do not know, but even short-term protection would be very useful for controlling clusters of COVID-19. How often do we need to be vaccinated? How well do these vaccines work in populations we want to protect most, like the elderly, those with diabetes or other underlying conditions, and other high-risk groups?

Is the vaccine effective in preventing people from getting the virus or developing symptoms? (As explained in a previous blog, asymptomatic people can be highly contagious.) Importantly, the results from Moderna suggest that the vaccine not only prevents infection, but also reduces the severity of infection. What happens if we vaccinate someone already infected with the virus and who tests positive for antibodies? Ensuring vaccine safety is critical to success, so safety must be thoroughly assessed.

In addition, the logistics of vaccine production and distribution could delay the whole process. For example, one notable difference between the vaccines from Moderna and Pfizer is their cold storage requirements. The Moderna vaccine must be shipped and stored long-term at minus 4 degrees Fahrenheit – standard freezer temperature. Pfizer’s vaccine requires minus 94 degrees Fahrenheit, which means special super-cold freezers are needed to transport and distribute the company’s vaccines. That can be a huge challenge for many resource-constrained areas, although Pfizer and BioTNech announced improvements to overcome the barrier.

Mass producing and distributing millions of doses of coronavirus vaccine globally by the end of the year will be logistically complex.

What are the next steps?

We will wait for final clinical trial results and their publication, as well as full approval by the FDA and European regulatory agencies. Then, the first vaccinations will begin, likely among health care workers and the most vulnerable individuals. Vaccination of these high-risk groups may begin in the United States by the end of this year and in Europe by early 2021. Every country is preparing; many governments, particularly in the United States, have secured substantial quantities of vaccine. However, mass vaccination of the broader public will only begin in the spring or summer of 2021.

So, this not the end of the story for vaccines against COVID-19. It is actually the first turn in the race. Many other types of vaccines in the pipeline will soon be evaluated and could offer important, possibly long-term, protection.

All these vaccine developments forebode a bright future. However, the vaccine alone will not end this pandemic. Mask wearing, hand washing, social distancing, rapid diagnostics and new treatments, including preventive therapies, cannot be forgotten if we want to curb COVID-19.

Both the Pfizer and Moderna COVID-19 vaccines must be transported and stored at low temperatures, which can present challenges for distribution in under-resourced areas.

Types of vaccines in development

As of Nov. 12, 48 COVID-19 candidate vaccines were undergoing clinical evaluation, according to a report from the World Health Organization (WHO). Most research efforts focus on the following vaccine types:

Virus-Based Vaccines	These vaccines employ a virus rendered inactive or weakened so it will not cause COVID-19 infection, but still produces an immune response.
RNA/DNA (Nucleic Acid) Based Vaccines	This brand new technology harnesses genetically engineered DNA or RNA of the virus’s protein to prompt an immune response. The vaccines from both Pfizer and Moderna are mRNA-based. The mRNA is injected into human cells, which churn out many copies of the coronavirus protein — in this case, the spiked protein on the COVID-19 virus’s surface. This type of vaccine trains the immune system to recognize and block the virus when exposed to it.
Viral Vector Vaccines	A harmless virus, such as an adenovirus or lentivirus, is engineered to deliver SARS-COV-2 protein genes into the body so that the spike protein can be safely produced and stimulate an immune response.
Protein-Based Vaccines	This approach delivers the immune system-simulating antigen to the body. SARS-CoV-2 proteins, such as the spike protein, are used to induce an immune response. The vaccine is usually administered in multiple doses and combined with adjuvants (ingredients) to enhance immunogenicity. One of GVN’s corporate partners, Sanofi, is working on the Phase I/II study of its protein-based COVID-19 vaccine.

Coronavirus vaccination of high-risk groups may begin in the United States by the end of this year and in Europe by early 2021. Both the Pfizer and Moderna vaccines require two doses, separated by several weeks.

Dr. Florian Kramme from Icahn School of Medicine in New York, one of the GVN Centers of Excellence, published a comprehensive overview of SARS-CoV-2 vaccines in development in the journal Nature. Dr. Kevin Sneed, dean of the USF Health Taneja College of Pharmacy, also recently published a very informative blog post about COVID-19 vaccines.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

October 28, 2020

Is there a link between the gut microbiome and COVID-19?

Several major U.S. news outlets are reporting that the United States is heading towards another peak of COVID-19 cases. Coincidentally, the French government issued a curfew order to major cities, including Paris, while battling to contain record numbers of COVID-19 infections. Italy has also broken its highest daily COVID-19 case record. As the world’s cases continue to climb, many unknown factors and understudied areas may be associated with coronavirus infections and possibly delineate novel opportunities to prevent and mitigate COVID-19. One is the interplay between the gut microbiome and the viral infection.

3D illustration of peptostreptococcus, bacteria that are part of human microbiome in the intestine and can cause inflammation.

What is the gut microbiome?

The human gut microbiome is made up of a huge numbers of bacteria, viruses and other microorganisms that inhabit our body. These gut microbiota play an important role in our immune system’s capacity to defend against infections and in regulating our metabolism, thus affecting our overall physiological status. Nutrition, diet, age and other environmental factors help shape the gut microbiome and immunity. Crucial cross-talk between the intestinal microbiota and the lungs is called the “gut–lung axis”. Bacteria produced in the gut can send signals through the blood to affect the lungs; in turn, inflammation in the lungs also affects bacteria populations in the gut.

Evidence mounts for effects of viral infection on the microbiome

Gastrointestinal symptoms, such as nausea, vomiting, or diarrhea, are common in COVID-19 patients. These symptoms are accompanied by intestinal damage or inflammation, which may contribute to the cytokine storm, a major overreaction of the immune response.

At the beginning of this pandemic, a study published in the journal Nature Medicine reported that SARS-CoV-2 virus was detected by anal swabs and fecal samples in more than 50% of COVID-19 patients. Recently, the Chinese University of Hong Kong conducted a small pilot study to investigate changes in 3 Dthe fecal microbiomes of patients with SARS-CoV-2 infections. The study showed that the fecal microbiomes of COVID-19 patients were significantly altered compared to those of the control group. We also know SARS-CoV-2 causes lung infections through the angiotensin-converting enzyme 2 (ACE2) receptor on host cells. Interestingly, ACE2 expression is increased in the digestive tract of COVID-19 patients and this may provide possible routes for SARS-CoV-2 infections. Collectively, this points to a potential prolonged effect of SARS-CoV-2 infection on the gut microbiomes of patients with COVID-19.

An interesting hypothesis has emerged that intervening in the gut microbiome composition, for instance by using pre-probiotics and/or nutrient-based therapies, might help prevent or mitigate COVID-19.

USF Microbiome Initiatives

The interplay between the microbiome and COVID-19 is at the forefront of USF’s research hub on “Microbiomes, Immunology and Infection Mitigation,” coordinated by Dr. Shyam Mohapatra and Dr. Christian Brechot. The hub’s activities merge transdisciplinary research and clinical projects. For example, Dr. Asa Oxner of the USF Health Morsani College of Medicine is working with Rutgers University to study the modulation of gut microbiota with an investigational dietary fiber-based nutritional regimen for the early treatment of COVID-19 patients with type 2 diabetes.

Meanwhile, the University of South Florida Initiative on Microbiomes has partnered with the Global Virus Network to offer the online course “Microbiomes and their Impact on Viral Infections.” Taught by world-renowned experts, this certified, noncredit course will provide students with the latest knowledge on the important role of the microbiome in preventing, mitigating and treating diseases. The course is open to anyone interested in learning more about the microbiome. More information of the course can be found here.

Overall, evidence now exists to support that intestinal microbiota impact the severity and disease progression of COVID-19. Understanding how the gut microbiome interacts with the respiratory system, as well as the immune response to the virus, should be useful in developing potential treatments or preventive measures for SARS-CoV-2.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

October 7, 2020

Understanding super-spreading in the fight against SARS-CoV-2

The COVID-19 pandemic continues spreading in many areas worldwide and, despite huge efforts, very few candidate therapies exist. Similarly, while promising, getting a safe and efficient vaccine remains a significant challenge.

We have transitioned from a crisis to a new era in the fight against COVID-19. Although we cannot precisely predict the pandemic’s evolution, experts have widely predicted a second wave of COVID-19 and long-term circulation of SARS-CoV-2. In addition, no matter how the pandemic evolves, over the next years we will face the risk of new and fatal viral infections, mostly zoonoses (diseases transmitted from animals to humans).

With this in mind, scientists from the Global Virus Network (GVN), a network of 57 research centers worldwide, brought their collective expertise to a two-day virtual workshop hosted by GVN. They convened to better appraise which lessons we should learn from our handling of COVID-19 and to determine best practices in preparation for potential future pandemics.

These leading scientists emphasized that rapid diagnostic testing, repurposing drug therapies, and vaccines targeting innate immunity are major factors in mitigating COVID-19. Read the full executive summary of the workshop here.

One of the key findings about SARS-CoV-2 and COVID-19 research addressed the role of “super-spreaders” and “super-spreading” events. The GVN scientists believe that both are major drivers of the pandemic, indicating that only a handful of those infected seem be highly contagious. Furthermore, short-range aerosol-driven transmission contributes to the dissemination of the virus, particularly at the super-spreading events.

Super-spreaders and super-spreading events are not new terms in infectious diseases. They have been documented in many infectious diseases, including typhoid, tuberculosis, measles, Ebola, and SARS-CoV-1 in 2003.

Who are super-spreaders?

Super-spreaders are the relatively small number of highly infectious individuals who disproportionately contribute to most of the virus transmission. After studying the cluster of SARS-CoV-2 infections in Hong Kong, a group of scientists at the University of Hong Kong published a preprint indicating that 20% of cases were responsible for 80% of the local transmission. However, what makes super-spreaders so contagious is still an enigma. We know that many are young, and can also be asymptomatic, an important factor favoring viral spread.

What are super-spreading events?

Super-spreading events are gatherings of large groups of people, which lead to unusually high numbers of viral infections. Nebraska Medicine, a GVN Center of Excellence, pointed out that these crowded events have venue, ventilation and vocalization in common. Most happen indoors and in confined spaces with close contact between people. People stay together in one place with limited fresh air. There is plenty of talking, yelling or singing, which can aerosolize the virus.

The Biogen leadership conference in Boston in late February is among several well studied super-spreading events during the COVID-19 pandemic. Ninety-nine cases were reported from this biotech company conference. A recent study analyzed SARS-CoV-2 genomic epidemiology primarily in the Boston area and presented further findings in a preprint paper. The researchers discovered that about 3% of the SARS-CoV-2 virus genomes sequenced nationwide, and 1.6% worldwide, had a unique genetic marker consistent with the results of the Biogen meeting.

Meanwhile, aerosol-related transmission remains a controversial issue. Yet, GVN scientists emphasize that short-range aerosol-driven transmission contributes to the dissemination of the virus, particularly in the context of super-spreading events. While very efficient against large respiratory droplets, masks are unfortunately less useful in blocking the tiny aerosolized droplets.

How can we prevent them?

Understanding the mechanisms of super-spreaders and super-spreading events can help us prevent them. So, what we should do to protect ourselves?

First, as we’ve repeatedly emphasized, mask wearing, handwashing and social distancing are critical to controlling the spread of the virus. Try to avoid large gatherings whether they occur inside or outside. When you must stay indoors with others, try to minimize the time spent together and choose venues with better ventilation systems.

Second, after COVID-19 cases are confirmed, contact tracing and quarantine should take place rapidly to limit transmission.

Finally, viral sequencing and phylogenetic analysis can provide immediate actionable insights as well as a better understanding of outbreak dynamics. More studies should be conducted to identify novel biomarkers capable of better defining the contagious potential of infected individuals.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

September 16, 2020

What will life be like after COVID-19?

As the global death toll from COVID-19 approaches 931,000, the world cannot wait for this pandemic to end. According to a World Health Organization report, so far 35 COVID-19 vaccine candidates are undergoing clinical evaluation, with the goal of recruiting more than 280,000 participants from at least 470 sites in 34 countries. Meanwhile, the U.S. Food & Drug Administration has authorized five COVID-19 treatments for emergency use. One question looms: Will our lives ever return to prepandemic normal after a vaccine or treatment is in place?

Even when a vaccine is ready, life will be different after the COVID-19 pandemic.

Even after the COVID-19 vaccine becomes available, life will be different in 2021 or even over the next several years. There are several reasons.

First, even when a vaccine is distributed, scientists still need to track its long-term safety and effectiveness. How long does protective immunity last after vaccination? How effective is the COVID-19 vaccine at reducing infection or sickness?

Second, will it work against potential new epidemics of related coronaviruses? In other words, can we dream of a “pancoronavirus” vaccine?

Third, will a sufficient proportion of the population get vaccinated? To end the pandemic, 55-80% of a population must achieve immunity either through infections or a COVID-19 vaccine. Yet, opposition to vaccination has exploded since the beginning of the pandemic.

Taking into account these yet-to-be-answered questions, here are some changes we foresee after COVID-19:

Mask wearing

Preventive measures against infectious diseases, such as wearing masks and maintaining good personal hygiene, will become routine for most. In the early days of the pandemic in the U.S., the use of masks was controversial. Later, the Centers for Disease Control and Prevention (CDC) issued recommendations about wearing masks in public settings, or where other social distancing measures are difficult to maintain. Months later, scientific evidence continues to mount about the benefit of wearing masks to reduce spread of the virus. In many Asian countries, wearing masks is already an important way to control infectious diseases, and this practice will likely become the new norm for people all over the world.

In many Asian countries, wearing masks is already a routine and important way to control infectious diseases.

Mental health

As noted in our April 15 blog, collective and individual psychological effects can last long after the outbreak ceases. The emotional well-being of health care professionals, patients who recover from COVID-19, and entire communities must be addressed both during and after any disaster, including pandemics. Appropriate approaches should be implemented to overcome the impact of post-crisis psychological distress.

Travel

The current pandemic has no doubt greatly affected the way we travel and will continue to do so. Many countries restrict internal and cross-border travel to reduce the spread of the virus. With many countries reopening and the holiday season approaching, many people are struggling to decide whether to travel, especially by air, or stay home. The CDC still recommends avoiding unnecessary or nonessential travel, whether for business or leisure. According to an editorial published in The Lancet Infectious Diseases, future airplane passengers can expect less inflight services, enhanced cleaning protocols, personal protective equipment that both crew members and passengers need to wear, and contact-free technology to facilitate payment and processes linked to travel.

Many people are struggling to decide whether to travel, especially by air.

Workplace

Many of us have been working from home since the SARS-CoV-2 pandemic began. Even if many businesses reopen, working from home may become permanent for many employees. When working remotely is not possible, employers may adopt a mixed work style. At the same time, both employers and employees should consider how to motivate those who work from home to engage in daily business activities and maintain or even increase their productivity.

Global preparedness and response

During this pandemic, we have lacked unified and multidisciplinary preparedness and response strategies. The approaches of governments vary widely. Thus, the outcomes are very different. Some countries have successfully reduced their cases to low levels, but many countries still struggle with reducing transmission of the virus. We must find solutions because the COVID-19 pandemic is far from over, and we may well experience other outbreaks in the future.

Overall, it is now critical to take a step back and thoroughly analyze what went wrong so far in our handling of the pandemic and what measures have succeeded. We must also discuss how to better harmonize the mitigation strategies from the different countries. Finally, we need to delineate our major scientific and medical successes as well as the challenges to be overcome in the next months and years. With this in mind, the Global Virus Network, an international network of 57 centers worldwide, will host a special annual meeting this month to address a global pandemic scenario analysis and help define how to prevent, or prepare for, a second wave of COVID-19 as well as future pandemics.

COVID-19 responses and outcomes have differed across the world.

In conclusion, COVID-19 will not disappear anytime soon and influenza season is right around the corner. So, until a vaccine is safe and sound to use widely, we should do all we can to protect ourselves and others.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

August 26, 2020

Neutralizing antibodies: Exploiting COVID-19 weak spots

With many schools beginning this fall, the need for COVID-19 treatments and vaccines is more urgent than ever. While researchers continue working around the clock to develop reliable vaccines and therapies, neutralizing antibodies (nAbs) are receiving valuable attention as a potential way to prevent and/or treat SARS-CoV-2.

What are neutralizing antibodies?

Antibodies are proteins naturally produced by the human immune system to fight infectious pathogens, such as the SARS-CoV-2 virus. NAbs prevent viruses from entering cells to launch infection by binding to the cell surfaces. A cohort study recently published in JAMA Internal Medicine found that neutralizing antibodies were detected in most of the 175 patients recovering from mild SARS-COV-2 infection. However, the viral concentration varied greatly at discharge. In addition, neutralizing antibodies were not detected in 10 patients. This means that many people’s immune systems are likely to produce antibodies strong enough to counteract SARS-CoV-2 when exposed to the virus; however, it is doubtful whether they will produce enough useful antibodies. The good news is that nAbs can be manufactured. NAbs produced in a laboratory are called monoclonal antibodies.

Monoclonal antibodies are produced by cloning a single B-cell. These lab-made antibodies recognize unique epitopes, or binding sites, on a single antigen (substance that induces an immune response) and act like human antibodies in the immune system. They are injected directly or intravenously into the body. Monoclonal antibodies are already used for many different clinical indications, such as cancers, asthma and osteoporosis. So, how do monoclonal antibodies fight against SARS-CoV-2?

Targeting the SARS-CoV-2 spike protein

As mentioned in our April 1 blog, SARS-CoV-2 particles have proteins called spikes protruding from their surfaces. The spike protein (S protein) contains two subunits, S1 and S2. S1 contains the receptor binding domain (RBD), which binds to the angiotensin-converting enzyme 2 (ACE2) receptors on host cells. The S protein conveys the virus to receptors on the host cell surface, helping the virus efficiently invade the human cell to produce more viruses.

In the search for nAbs against SARS-CoV-2, many studies have focused on the RBD of the S protein to block the ACE2 receptor binding. An article in Science suggests that, when considering vulnerable spots of COVID-19 to be attacked, the focus should be on intact spike proteins, including the N-terminal domain (NTD). NTD is another major domain of S1, but the NTD of SARS-CoV-2 does not bind to the ACE2 receptor. The role of NTD in SARS-COV-2 infection should be further investigated.

Research and development of antibodies that “neutralize” the COVID-19 virus may provide a prevention and/or treatment option until a vaccine is available.

Interestingly, another article published earlier in Nature supports this conclusion. A team of scientists from Columbia University isolated 61 antibodies from five patients with severe COVID-19. Nineteen of the 61 monoclonal antibodies robustly neutralized the virus, with those directed against the RBD and those directed against the NTD evenly divided. The team also conducted an experiment in an animal model to demonstrate the potency of these monoclonal antibodies and to highlight NTD as a target for potentially treating and/or preventing SARS-CoV-2.

Infection protection while awaiting vaccines

Monoclonal antibodies may offer a short-term protection from SARS-CoV-2 while we wait for reliable vaccines, especially for vulnerable populations such as nursing home residents, people with underlying diseases, health care providers, and the elderly. Earlier this month, the National Institutes of Health announced two additional Phase 3 randomized, placebo-controlled, double-blind clinical trials testing whether experimental monoclonal antibodies can prevent infection by SARS-CoV-2.

Thus, neutralizing antibodies, whether natural or monoclonal, may block initiation of the infection cycle and possibly treat an established infection by directly targeting different parts of SARS-CoV-2’s S protein. This strategy might be extremely valuable while waiting for an efficient vaccine. It can also complement therapies being evaluated for COVID-19 prevention in at-risk individuals.

Coronavirus depicting spike proteins on cell surface

Like other coronaviruses, SARS-CoV-2 particles are spherical with proteins called spikes protruding from their surface.

However, nAbs also have limitations. For example, determining the doses to be injected is not that simple. Mutations of SARS-CoV-2 virus might allow the virus to develop resistance to nAbs. Furthermore, at least theoretically, we cannot exclude that these molecules might worsen the outcome of SARS-CoV-2 infection, a phenomenon known as antibody dependent enhancement. This possibility must be evaluated carefully before moving to treat humans.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

August 5, 2020

Cleaning, sanitizing and disinfecting against COVID-19: What’s the difference?

Nearly a half million COVID-19 cases were confirmed in Florida as of Aug. 4. By now, we hope everyone understands the importance of wearing face masks, maintaining social distancing, and practicing good personal hygiene in controlling the spread of SARS-CoV-2 and containing the pandemic. Over the past few months you have no doubt practiced at least one, if not all, of the following three processes: cleaning, sanitizing and disinfecting. So, what are the differences and how can each be used to help prevent COVID-19 infection?

In this context, we don’t intend to recommend any products or teach you how to make homemade solutions, but to explain the differences.

Based on Centers for Disease Control and Prevention (CDC) guidelines, cleaning means to remove the germs, dusts or dirt from surfaces or objects through scrubbing, rubbing or washing. Sanitizing significantly reduces the growth of viruses, bacteria or germs on surfaces or objects. Sanitizers are referred to by the U.S. Environmental Protection Agency (EPA) as antimicrobial solutions or devices that can reduce microbiological contamination to meet the public health standards or requirements.

Disinfecting kills or inactivates bacteria, germs or viruses on surfaces or objects. Disinfectants are more effective than sanitizing or cleaning products, so they must meet more rigorous EPA testing standards. Both sanitizing and disinfecting processes can be used after the cleaning process to further lower the risk of spreading infection. For example, during influenza season, it’s highly recommended that schools or communities clean, sanitize and disinfect their facilities daily to reduce the spread of flu.

Let’s be clear; disinfection is not a panacea. Sometimes, disinfecting is not as good as a simple cleaning or sanitizing process. Before deciding which is applicable or more efficient, you need to evaluate your situation. The CDC has issued a guidance for Cleaning and Disinfecting Public Spaces, Workplaces, Businesses, Schools, and Homes.

Cleaning

Regardless of the presence of the pandemic, every person, household and community should maintain a good cleaning routine. Thoroughly cleaning your home or work environment can provide many benefits, such as reducing allergies and stress. Regular cleaning is enough for infrequently touched surfaces or objects, and unoccupied rooms, sidewalks, parks or other spaces.

Sanitizing

Surfaces, such as kitchen countertops and cutting boards, that come into contact with food (especially raw meat) and beverages, should be sanitized using appropriate methods. Chemicals are not necessary for some sanitizing processes. For example, steamed heat can reduce or kill certain germs and bacteria. Some products work as both sanitizer and disinfectant. Be sure read the label before using.

Disinfecting

Frequently touched surfaces should be disinfected routinely. These include light switches, door handles, handrails, elevator buttons, faucet handles, tables, cell phones, laptops and other electronic devices. Even when social distancing is applied, shared spaces or those occupied by many people — hospitals, clinics or homes with sick patients, for example — should also be disinfected regularly. The Global Virus Network recently published an important update about disinfection strategies against COVID-19. Interestingly, a paper published 15 years ago concluded that commonly used disinfectants, such as isopropyl alcohol (rubbing alcohol) with concentrations of 60% or more, could inactivate SARS-CoV-1; this is also effective for SARS-CoV-2. However, before using any disinfecting products, please check whether the product is included in EPA List N, an updated list of more than 400 surface disinfectants that meet the agency’s criteria for use against SARS-CoV-2.

Different voices

Recently, different voices have been raised regarding cleaning, sanitization and disinfection in stopping the spread of COVID-19 virus. A Comment recently published in The Lancet stated that contaminated objects that have not been in contact with an infected carrier for many hours do not pose a measurable risk of transmission in non-hospital settings. In other words, surface transmission seems rare in COVID-19 cases. The paper also suggested peer-reviewed studies are needed to determine the COVID-19 virus’s survival rate on different types of surfaces in real-life settings. Yet, we still must be careful and pay attention to surface transmission.

Whatever product or process you decide to use to reduce your risk of COVID-19 viral infection, remember safety. Always wear proper protective equipment when working with chemicals, follow the label instructions, avoid mixing chemicals, safely store the products/devices, properly handle waste, and last, but not least, never eat, drink or inject any of the products.

Finally, please do not let cleaning, sanitizing and disinfecting give you a false sense of security. To fully minimize our risk, we must remain diligent about wearing masks, keeping social distancing and avoiding crowds.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

July 22, 2020

Is it time to shift to a saliva test for COVID-19?

As COVID-19 continues to spread in most U.S. states, the 7-day moving average daily percent of positive tests in Florida has reached 18.7%. Months after the first outbreak of this pandemic, we all know SARS-COV-2 diagnostic tests are vital for immediately identifying an infectious cluster, tracking transmission, and managing treatment and overall prevention of the virus’s spread.

In our April 1 blog, we described the standard SARS-COV-2 diagnostic test — real time reverse transcription-polymerase chain reaction (rRT-PCR) detection of the COVID-19 virus from a nasal or throat swab. A 6-inch-long swab is inserted into the nose or throat to collect samples for analysis. The whole process should take no more than 15-20 seconds if performed correctly. Does the test hurt? Not necessarily, but the process can be uncomfortable. Are any other tests available? Yes, we also have another test method called the antibody test. Blood needs to be drawn and analyzed for antibody response to the virus.

A health care worker collects a specimen using a nasal swab at a COVID-19 mobile testing site.

How reliable is saliva for detecting SARS-CoV-2?

In this blog, we’d like to review a new diagnostic test based on saliva samples. Like nasal swab testing, it is an alternative way to collect specimens and detect the presence of SARS-CoV-2, rather than checking for antibodies against the virus. Like many DNA tests self-administered at home, the saliva sample is collected by spitting into a test tube and mailed to a laboratory for testing. The test uses a method similar to the rRT-PCR nasal swab test, which converts the specimen’s RNA into DNA and rapidly amplifies it to detect tiny genetic pieces of the virus. If genetic material of pathogen SARS-CoV-2 is present, the patient is diagnosed with COVID-19.

Is the saliva test reliable? Saliva has been shown in several studies to be a promising specimen for diagnosis, surveillance and prevention of COVID-19. For example, a study published in Clinical Infectious Diseases demonstrated that 91.7% of patients detected COVID-19 virus in their own saliva. Another study, later published in the Journal of Infection, confirmed that saliva samples from 25 COIVD-19 patients tested positive for SARS-COV-2. Further study at Yale University found that saliva was more sensitive than nasopharyngeal swabs. Saliva is a common agent for transmitting viruses, such as SARS-CoV-1, MERS and Ebola. Different sizes of saliva droplets are generated by sneezing, talking, or even breathing. Overall, saliva tests have yielded many accurate results for SARS-CoV-2 RNA detection.

Several studies have shown saliva to be a promising specimen for COVID-19 diagnosis, surveillance and prevention.

Advantages of the saliva test

Saliva testing has many benefits:

It is noninvasive and more comfortable. Samples are easier to collect compared to nasal swab and antibody blood tests. States are being urged to reopen their schools, so saliva might play a very important role in testing populations of children because the process is not as scary for them. Children up to 10 years old are less likely to develop severe illness from SARS-CoV-2 and less likely to transmit the virus; yet, those older than age 10 (i.e., in middle and high schools) were recently shown to potentially transmit the virus, especially in the context of a high-virus circulation level. Thus, the risk of transmitting the virus to other vulnerable family members, such as grandparents, should not be underappreciated, and children should be extensively tested to better contain the pandemic.
With appropriate guidance, the collection and screening of saliva samples can be managed at home and repeated multiple times. That significantly reduces the risk of infection among health care workers who administer nasal swab or antibody tests. In May, under an emergency use authorization, the U.S. Food & Drug Administration approved the first diagnostic test with the option of using home-collected saliva samples for COVID-19 testing.
The diagnostic test is less costly due to its simple process, allowing health care personnel and protective equipment to be saved for when they are most needed.
Test volume can be easily increased compared to other methods. Saliva collection and screening can scale up without the need for fully functioning testing centers.

Saliva-based COVID-19 testing — with a simpler, more comfortable, and less costly collection process than nasal swab or antibody testing — may offer an option for timely testing of students when schools reopen. Studies continue to evaluate the reliability of this test method.

Even though many studies have shown reliable results, it is still uncertain whether the saliva test is as sensitive, if not more sensitive, than the nasal swab method in correctly generating a positive result for people who have COVID-19. Several institutions across the globe are conducting ongoing studies testing the reliability of saliva tests to detect COVID-19 virus. No firm conclusions should be drawn until the peer-reviewed studies are complete.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

July 8, 2020

Can SARS-CoV-2 be spread by floating airborne particles?

Over the past few weeks, the spread of COVID-19 in geographic areas such as Latin America, the U.S. and India, has been rather daunting. Has the second wave arrived, or has the first wave never left? The COVID-19 case reports from the three countries mentioned all show an ascending curve. So, the first wave of COVID-19 is far from over in these countries. While we have learned a lot about the current pandemic, much remains uncertain. For example, one hot topic is whether SARS-CoV-2 is airborne. 239 scientists worldwide supported a recent Clinical Infectious Diseases commentary recommending precautions against potential airborne transmission of SARS-COV-2 to control the increase in cases as countries reopen.

What is airborne transmission?

Airborne coronavirus has been a bone of contention for many scientists since this pandemic started. As mentioned in our May 13 blog, the two major routes for transmission of the COVID-19 virus are person-to-person through respiratory droplets and by direct contact. Today what worries us most, however, is potential spread of infection from microscopic droplets (aerosols) exhaled by contagious people without symptoms.

According to the World Health Organization, airborne transmission occurs when infectious agents, contained within droplet nuclei in aerosols, persist long enough for others to inhale the virus particles. It is important to understand that many public health agency recommendations are based on older studies. In fact, a perspective published in Science noted that in still air, a 100-μm droplet will settle to the ground from 8 feet in 4.6 seconds, whereas a 1-μm aerosol particle will take 12.4 hours. Also, droplets produced by coughing or sneezing can be aerosolized and travel across an enclosed space.

The perspective also suggested that the CDC’s 6-feet-apart social distancing guideline may not be enough in many indoor environments. In spaces with inadequate ventilation aerosols can stay suspended in the air for hours, accumulate over time, and move more than 6 feet with the air flow. That means that by talking, or even breathing normally, you can get infected with airborne diseases, such as tuberculosis and measles. Interestingly, an article published 16 years ago in the New England Journal of Medicine cited SARS-CoV-1 investigations that concluded only airborne transmission appeared to explain the large community outbreak at the Amoy Garden in Hong Kong.

So, is SARS-CoV-2 airborne?

The simple answer is that it is too early to either draw a solid conclusion or to rule out reasonable doubt. Based on a study published in Nature, scientists in China measured the viral RNA of SARS-CoV-2 in two Wuhan hospitals in February and March this year. Their analysis identified the spread of viral RNA in aerosols in isolation wards and ventilated patient rooms. The good news is that the amount was very low when proper sanitization and ventilation was performed. Also, after thorough sanitization, previously high concentrations of aerosolized SARS-CoV-2 RNA in some medical worker areas were reduced to undetectable levels. Of note, the researchers did detect higher concentrations of SARS-CoV-2 RNA in aerosols in patients’ toilet areas.

However, detecting viral RNA does not automatically imply the presence of infectious viral particles. More studies need to be done worldwide on the circulation of viral infectious particles, investigating different doses and sizes of droplets. Such research could help define how many aerosolized SARS-CoV-2 particles must be inhaled to get infected.

What should we do?

Although current scientific evidence is insufficient to conclude that SARS-CoV-2 can be transmitted through aerosols, we fully support the recommended precautions, recently published in scientific journals, to address potential airborne spread of COVID-19. Good indoor ventilation, avoidance of crowds, proper household disinfection, and open spaces can limit the risk of airborne transmission. These protective measures are simple and inexpensive to implement.

Also, never forget to wear face masks. Masks provide a critical barrier and reduce the likelihood and severity of COVID-19 by significantly reducing the concentration of the virus in the air. The aerosol filtering efficiency of homemade masks using different materials, thicknesses, and layers was recently found to be similar to that of tested surgical masks. Thus, it comes as no surprise that countries implementing universal masking, such as Taiwan, Japan, Hong Kong, Singapore, and South Korea, have been most effective in reducing the spread of COVID-19.

By combining methods to reduce the risk of airborne COVID-19 virus transmission indoors with wearing masks, social distancing and good personal hygiene, we can all do our part to curb the pandemic.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

June 24, 2020

Dexamethasone: Has an old drug ushered in a new era?

With total COVID-19 deaths surging past 469,000 this week, an old drug called dexamethasone continues to capture the worldwide attention of media and clinical literature. Almost every major news outlet has published, or broadcast stories related to this common steroid medication that has been on the market for over 60 years.

What prompted all the enthusiasm?

It all started with the news release reporting initial results of a randomized, controlled clinical trial from the University of Oxford. According to the release, more than 2,000 COVID-19 patients received randomized low-dose dexamethasone treatment. This treatment group was compared with over 4,000 patients who received routine care only. Dexamethasone administered either orally or by intravenous injection was found to reduce the number of deaths by one-third, one-fifth and zero, respectively, in patients on ventilators, on oxygen, and without any respiratory support.

These initial findings have shown dexamethasone to be the first drug to reduce deaths among COVID-19 patients. The World Health Organization welcomed the preliminary results and the lifesaving scientific breakthrough for coronavirus patients with severe respiratory complications.

What is dexamethasone and how does it work?

Dexamethasone is a long-acting corticosteroid used to treat numerous health conditions, including severe allergies, arthritis, asthma, skin conditions, inflammation, and adrenal insufficiency. Although the drug is widely prescribed for many different diseases, the effectiveness and safety of corticosteroids to treat COVID-19 patients remains highly controversial. As mentioned in our May 20 blog, SARS-CoV-2 can trigger hyperinflammation in the lungs and lung lesions in about 5-10% of patients with clinical symptoms. This is linked to a major overreaction of the immune response, called the “cytokine storm.” It can cause acute respiratory distress syndrome (ARDS) and multiple-organ failure in infected patients, leading to severe illness or death.

Steroids, like dexamethasone, prevent the release of inflammation-causing substances in the body. In other words, the drug does not target the viral infection but suppresses the body’s immune response. Well-established research indicates that the immune system should not be inhibited when the body is fighting against infection.

So, why does dexamethasone still work? We do not exactly know; the balance between stimulating and inhibiting the immune response to the virus is very delicate. One possible explanation is that the benefits of steroid treatment outweigh its potential harm in patients experiencing a critical medical condition. Indeed, the drug produced more promising results in patients on ventilators or receiving supplemental oxygen; there was no benefit for those who did not require respiratory support, that is, they had less severe disease. Clearly, more studies are needed on the immune profiling of such patients.

The benefits and limitations

No doubt, initial results reporting that dexamethasone cuts the risk of death in the sickest patients with coronavirus infection are remarkable. Another significant benefit is the low cost of the drug, which is widely produced in many countries. Last week, both the British government and South Africa Health Ministry approved dexamethasone to treat severely ill COVID-19 patients. Dexamethasone could also open a door for treatment of non-COVID-19 patients who have severe respiratory failure— although anti-inflammatory drugs were initially considered toxic, based on previous experience with influenza.

This clinical trial also has limitations. Modifying immune response must be carefully evaluated. We have learned how difficult it can be to control potential side effects when treating patients with sepsis. Although the Oxford study states that dexamethasone had no adverse effects, the research needs to be peer-reviewed and reproduced to reach full conclusions.

In addition, it would be interesting to evaluate the effectiveness of dexamethasone in combination with antiviral drugs like remdesivir to treat SARS-CoV-2. Peer-reviewed data shows that remdesivir — which directly targets the virus itself by blocking a key enzyme it needs to replicate — shortens hospital stays for COVID-19 patients. Further studies should carefully investigate whether these two therapies could improve outcomes jointly, rather than using each separately.

Dexamethasone illustrates the impact of an unbiased drug repurposing strategy. More definitive data are needed to make this old drug a new standard of care for critically ill COVID-19 patients.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

June 17, 2020

Risk of COVID-19 transmission by presymptomatic vs. asymptomatic patients

Whether or not COVID-19 infected patients with no apparent symptoms (asymptomatic) can transmit the virus tremendously impacts the global public health strategy against SARS-CoV-2 infection. In this week’s blog, we wish to clarify the distinction between asymptomatic and presymptomatic carriers of COVID-19, their risk of transmitting the virus and the critical need to identify a testing method before symptoms appear. We support the World Health Organization’s recent clarification and thank them for raising awareness of this critical issue.

What is presymptomatic?

We understand that distinguishing between asymptomatic and presymptomatic cases can be confusing. Asymptomatic was discussed many times in our previous blogs. But, what does presymptomatic mean? Presymptomatic transmission is the spread of SARS-CoV-2 from an infected person to another person before the source has developed symptoms. A recently published study in Nature has shown substantial transmission of COVID-19 before symptom onset. Shedding of the virus—the point at which an individual becomes contagious– may begin two to three days before the appearance of the first symptoms. This contrasts with what was observed with SARS-CoV-1 in 2003. A recently published editorial in The New England Journal of Medicine states that, although virus shedding was not quantitatively analyzed, 71% of samples cultured from patients at a skilled nursing facility yielded live viruses one to six days before symptom onset. After symptoms appear, the viral load decreases gradually. In general, as expected, higher rates of presymptomatic transmission were reported in geographic areas where SARS-COV-2 diagnostic tests have been widely used.

According to an article in Emerging Infectious Diseases, presymptomatic transmission occurs through generation of respiratory droplets as well as, possibly, aerosol or indirect transmission. It has been more challenging to quantify how asymptomatic individuals contribute to the transmission of SARS-CoV-2. Lack of quantitative analysis of viral shedding has hindered evaluating the role of “asymptomatic” individuals, those who are infected but display no symptoms. However, a recent study in Clinical Infectious Diseases reported that asymptomatic individuals may also show substantial viral shedding for potential transmission. More comprehensive studies are needed to draw a solid conclusion about the risk of COVID-19 transmission when comparing asymptomatic and presymptomatic individuals.

Challenge to identify infections before symptoms

Unfortunately, the COVID-19 pandemic is expanding because it remains difficult to trace mild or presymptomatic infections. We have learned a very important lesson from the initial response to the SARS-CoV-2 outbreaks. For instance, most countries worldwide delayed state and local responses, thus allowing SARS-CoV-2 to spread rapidly. A key issue has been testing. Symptom-based screening alone fails to detect a high proportion of infectious cases and is not enough to control overall transmission. Consequently, many countries have been locked down to prevent the rapid spread of COVID-19, because simply isolating patients may not be enough to contain the outbreak. Conversely, several countries, such as Australia, South Korea, Germany, Singapore, and Taiwan, managed to contain the virus early and have worked hard to keep it suppressed with efficient testing and a contact tracing system.

Until a reliable vaccine is widely available, or we develop effective screening to identify presymptomatic or asymptomatic virus carriers who are unknowingly contagious, we suggest the following:

Make sure to wear face masks, maintain social distancing of 6 feet or more, and practice good hygiene.
Young people at not invulnerable. SARS-CoV-2 is a highly contagious virus that can infect anyone, and even those without apparent symptoms can accelerate its spread to family, friends or others.
Governments and communities should embrace new technologies to efficiently trace previous contacts of patients diagnosed as contagious COVID carriers, regardless of the presence or absence of symptoms.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

June 10, 2020

The 1918 flu pandemic vs. COVID-19: What have we learned?

Many studies and articles have compared the flu pandemic of 1918-1919 to the COVID-19 outbreak that began in December 2019 (maybe even earlier). We are witnessing a very uncertain time with a flattening of the coronavirus curve in most but, by far, not all geographic areas. While many countries report a sharp decrease in cases and deaths, the pandemic persists in South America, India, and other areas. In fact, the number of infections is still increasing in Florida, although at a slow pace. Thus, we all wonder what will happen next. As with the 1918 flu pandemic, will a second, or even third, more deadly wave occur or will this latest pandemic end soon? First, let’s look back at what happened during the 1918 influenza pandemic.

Notice of the influenza epidemic of 1918 lying on the laboratory table of a medical research scientist studying the virus.

A brief history of the 1918 influenza pandemic

From 1918 to 1919, a devastating pandemic infected more than 500 million people worldwide (almost one third of the total population), and about 10% died. The disease was caused by an HIN1 virus that originated in birds. It was called the 1918 Influenza pandemic, also known as the Spanish flu. Ironically, the pandemic was not first detected in Spain. During World War I, unlike most other countries that fought in the war, Spain was a neutral zone. Without a wartime news blackout by Spain’s government, Spanish media reported freely on the severity of the illness and the country became associated with the origin of the pandemic!

According to an article published in the journal Emerging Infectious Diseases, the case-fatality rate was more than 2.5% worldwide (compared to less than 0.1% in other flu pandemics). In the U.S, the first case was identified among military personnel in spring 1918. Many American soldiers gathered before being deployed to Europe by ship. Air travel was not available at that time. Many soldiers developed “flu-like” symptoms, but most recovered rapidly. The more deadly wave struck in fall 1918. This second wave lasted six weeks and followed the troops from Sierra Leone to the U.S, spreading to almost all Europe and later Asia. By the end of the pandemic, more than 675,000 people had died in the U.S. and 50 million globally. Half of all the deaths occurred in the second wave. Many researchers believe this was caused by a mutated strain of the virus. The third wave in spring 1919 led to the end of the pandemic that summer due to herd immunity and massive deaths.

A century has passed since the 1918 influenza pandemic. Are there any significant similarities or differences to the current COVID-19 pandemic we are fighting? The answer is yes to both.

The similarities

Both viruses are transmitted via respiratory droplets. This means that the old- fashioned social distancing and quarantine measures that worked during the 1918 flu pandemic will work now as well. For example, an article in PNAS, reported that St. Louis, Missouri was one of the U.S. cities with the most effective public health interventions against the 1918 flu pandemic. The transmission rate was reduced around 30- 50%. The mortality rate was reduced only about 10%, because the measures were introduced too late and lifted too early. Conversely, Philadelphia was badly hurt because the city did not cancel massive gatherings. Does that sound like the current situation? We are not at war now. However, just as troops traveled worldwide during the 1918 flu pandemic, nowadays “global citizens” taking advantage of our more convenient transportation systems have contributed significantly to the spread of the COVID-19 virus between countries.

The white crosses of an historic graveyard cemetery in Norway, built after miners died during the 1918 influenza pandemic.

Furthermore, people living in poverty were more vulnerable to the 1918 flu pandemic virus, because they didn’t receive proper medical care or pay sufficient attention to personal hygiene. Low-income people in U.S. and in developing countries are also suffering disproportionately during the current pandemic. In the absence of vaccines and treatments, surveillance and contract tracing was implemented to contain the spread of the 1918 flu pandemic. Just like we are doing right now.

The differences

While many similarities can be drawn between two pandemics, there are also important differences. The most noticeable difference involves individuals at greatest risk. The elderly and those with underlying diseases are the most vulnerable to SARS-COV-2. In contrast, during the 1918 flu pandemic, young healthy people died at a higher rate. Why? One hypothesis proposed that the elderly people in 1918 had already encountered similar viruses in previous years and therefore were partly protected against infection. It is a good example of the “cross-immunity” phenomenon explained in our June 3 blog.

Another notable difference is today’s immersive improvements in data sharing. A century ago, the lack of health care infrastructures and providers made reporting cases difficult. The same was true for the development of new diagnostic tests, treatments and vaccines. In 1918, we did not have the technology or the capability to accelerate pandemic-related research that we can achieve today.

An elderly woman sitting in her home tries out the face mask she has handmade to wear during the 1918 influenza pandemic.

What have we learned?

Pandemics have rewritten the course of human history in their own unique ways. Is there going to be a second, or even third, wave of COVID-19? Maybe. However, we live in extraordinary times so we should keep our hopes up. This pandemic has been devastating for many, but we are witnessing the development of diagnostic tests, treatments and vaccines faster than ever before. Many organizations and institutions, including the Global Virus Network, continue devoting 100% of their efforts toward curbing the current pandemic. While we wait patiently for more promising results, make sure to wear your face masks, maintain social distance, and practice good hygiene.

Linman Li, MBA, MPH, PMP, CPH
Director, USF- GVN Center
USF Health Morsani College of Medicine
Vice President, Global Virus Network

June 3, 2020

The implications of COVID-19 cross immunity

What is immunity?

Knowing how immunity works against SARS-CoV-2 is critical for understanding the pathogenesis of COVID-19; developing diagnostics tests, neutralizing antibody-based therapies and vaccines; and standardizing protective and preventive measures.

Immunity is a state in which the body recognizes and resist to invading viruses, bacteria or other pathogens, mitigating their harmful effects. It prevents infection and maintains the integrity of the body by fighting, neutralizing and removing the pathogens. Most COVID-19 patients (symptomatic or asymptomatic) produce IgM and IgG antibodies within days to weeks of infection with SARS-CoV-2. The virus also induces a cellular immune response based on T cells, but we are still in the early days of understanding this T cell-mediated immunity.

However, an article recently published in the journal Cell by La Jolla Institute for Immunology at the University of California San Diego, a Global Virus Network (GVN) Center of Excellence, found that 40-60% of unexposed, healthy individuals developed T-cell immune responses to SARS-CoV-2 proteins. Blood specimens were collected from these study participants between 2015 and 2018, before the outbreak of COVID-19. That means although they had not been exposed to the new coronavirus, it appears that a good percentage had already raised an immune response, which could be partially protective against SARS-CoV-2!

One plausible explanation for this finding is cross-immunity.

What is cross-immunity?

Cross-immunity, or cross-reactivity, means that an antibody can recognize multiple structurally similar parts of pathogen proteins known as epitopes, even though they are located on different viruses. That enables the human host to efficiently defend itself against many potentially-threatening pathogens. The smallpox vaccine, for example, was developed after British doctor Edward Jenner observed that milkmaids infected with cowpox did not show any symptoms of smallpox; this led to administering as a vaccine material from smallpox sores (a process known as variolation).

Returning to the Cell article, individuals never exposed to SARS-COV-2 might show a cross-reactivity between SARS-CoV-2 and the other coronaviruses that cause the common cold. Similarly, another GVN Center of Excellence, Duke-NUS Medical School in Singapore, published a preprint on BioRxiv last week. The researchers noted that T cells reacting to SARS-CoV-2 epitopes were detected in nine out of 18 blood donors (50%) although they had neither been exposed to the first SARS virus (2003) nor SARS-CoV-2.

Understanding the mechanism of cross-immunity is increasingly important because antibodies are actively developed for diagnostics, vaccines, or treatment for various diseases. Indeed, a very important implication is that we might use cross-immunity to existing vaccines to reinforce protection against SARS-CoV-2. With this in mind, several studies are now evaluating the potential protective effect of the Bacille Calmette Guerin (BCG) vaccine, used to prevent tuberculosis. And the Institute of Human Virology at the University of Maryland, the first GVN Center of Excellence, leads a clinical trial testing whether the polio vaccine can induce innate immunity against SARS-CoV-2, and, possibly, interfere with its replication.

Human immunity to SARS-CoV-2 may be more widely distributed than we thought. According to an article posted by the American Society for Microbiology, 60-75% of children have antibodies to at least one coronavirus, and 90% of adults over age 50 years have antibodies to all coronaviruses causing the common cold. This may also have important implications for the mortality (deaths) caused by COVID-19. Is it plausible that different levels of cross-reactivity with coronaviruses explain why certain countries, regions or individuals would be more susceptible to SARS-CoV-2 or may experience higher morbidity and mortality rates even with social isolation and other protective measures? Yet, while cross-immunity is a very appealing concept, many other factors need to be considered. For instance, we know that age, gender, health status, diet, behaviors and other factors play a very important role in contributing to the severity of COVID-19 symptoms.

Cross-immunity may induce challenges as well as potential benefits. For example, we must ensure that cross-immunity with other coronaviruses does not cause COVID-19 diagnostic tests to show false positive results. Finally, cross-immunity might in theory contribute to what we call “antibody-dependent enhancement (ADE),” a phenomenon that generates vaccine side-effects. So far, no evidence exists that any of the vaccines in development worsen a COVID-19 virus infection, but we need to remain mindful of ADE as we monitor vaccine progress.

Clearly, more studies are needed, but cross-immunity remains an important field of research to decipher.

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

May 27, 2020

Where do we stand in the fight against COVID-19?

Did the curve really flatten?

Nearly five months after the first cluster of pneumonia cases (later identified as COVID-19) was reported on Dec. 31, 2019, has the curve really flattened?

As mentioned in our April 22 blog, there are many prediction models. In the U.S., for example, the Centers for Disease Control and Prevention cites 19 individual forecasts. All suggest that the number of deaths will continue to rise in the coming weeks, but at a much slower pace. Many states continue to loosen their restrictions. At the same time, coming off a long Memorial Day weekend, unfortunately the U.S. death toll approached 100,000. This accounts for almost 30% of all COVID-19 related deaths worldwide. At the same time, the situation is particularly alarming in South America.

While waiting for vaccines and treatments, we must innovate and identify more preventive solutions

According to the World Health Organization, we still have a long way to go in the COVID-19 pandemic. Last week, Spain extended its state of emergency for the fifth time until June 6. Meanwhile, Spain has announced it will reopen its borders to foreign tourists in July. This capricious pattern has repeated during the pandemic. Ironically, while we cannot fully foresee the course of the pandemic, we can certainly predict that the situation’s unpredictability will continue until a vaccine or treatment becomes available.

A new study published last week in The Lancet found that hydroxychloroquine or chloroquine may not help treat COVID-19 as has been claimed, but instead the drug may lead to a decreased hospital survival rate and an increased frequency of ventricular arrhythmias. However, the authors of this large retrospective analysis acknowledge that randomized prospective studies, such as those conducted at Tampa General Hospital, are still needed. Also, hydroxychloroquine is likely to be effective in the early stages of infection, rather than in critically ill pneumonia patients. Overall, these debates point to the importance of evaluating drugs that might prevent, not only treat, COVID-19. The FDA, for example, has approved two clinical trials to assess the potential of using the repurposed drug nitazoxanide, widely prescribed to treat intestinal parasites, to prevent COVID19 in nursing homes and among health care workers. These nitazoxanide trials are being initiated in Tampa Bay. Finally, identifying optimal ways to improve the effectiveness of masks and disinfecting solutions should also have a significant impact, and several teams at USF are working along these lines.

As with treatments, we have seen very promising, but still early results in vaccine development. So far, the interpretation of the studies is limited by the small size of the cohorts, short follow-up time, and the absence of randomized control groups. Two weeks ago, the company Moderna announced encouraging early results from a Phase 1 trial of its messenger RNA vaccine against the novel coronavirus. And last week, the The Lancet published a paper based on data from the COVID-19 vaccine developed by Cansino Biologics. This platform uses genetic material from a live but weakened human cold virus, adenovirus 5(Ad5), and SARS-COV-2 coronavirus, incorporating the latter into the Ad5 virus. The results appear promising, because antibodies and neutralizing antibodies increased significantly at day 14 after inoculation and peaked 28 days after inoculation in the three dose groups. Yet, does previous immunity against colds decrease the effectiveness of such viral vectored vaccines? In addition, we need to ensure not only effectiveness, but also safety of the vaccines.

Another question to be addressed: When a vaccine is available who, or which groups, should receive it first? It will be impossible to produce enough doses in a short time to protect the world’s population, so vaccination priorities must be determined. The principles established for distributing and implementing the use of COVID-19 testing kits should also apply to the vaccine. High-risk groups — including the elderly, people with underlying medical conditions, health care providers, and underserved populations — should be vaccinated before others. Standard protocols must be developed to meet the expected high demand but initially low supply of vaccines.

Summer is here, which means flu season is not far away. By fall, we may have to fight both COVID-19 and influenza. Please do not take the current ease of restrictions for granted. Continue to be diligent about social distancing and personal hygiene to protect your loved ones and yourself.

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

May 20, 2020

COVID-19: A perverse respiratory virus that attacks beyond the lungs

The overall COVID-19 mortality (death) rate is not known, but given the estimated number of asymptomatic infections it will not be very high, maybe about 0.3%. However, the highly contagious virus has had devastating consequences as it spread across the world. The mortality rate is much higher in older populations (10-15%) and in people with pre-existing conditions, such as diabetes, obesity, and chronic cardiovascular or pulmonary diseases.

This virus is so unusual and, in fact, perverse!

Each week we learn more about its capacity to damage the organs of infected patients who become critically ill. SARS-CoV-2 can trigger lung lesions in about 5-10% of patients with clinical symptoms. This is known to be associated with a major overactive immune response, known as the “cytokine storm,” which causes extensive inflammation in the lungs. We now also know that the virus can cause a loss of smell and taste (anosmia) and infect the brain with significant neurological consequences (see our April 29 blog on nicotine).

Lately, another deadly feature of the virus has emerged. That is, its ability to infect the endothelial cells that line blood vessels. These cells have very important functions in our body, including maintaining a proper cardiovascular balance. They also contribute to our immune status and defense against infections. Therefore, infection of endothelial cells and resulting inflammation of blood vessels may lead to severe dysfunction of vital organs, such as the heart, lungs, brain and kidneys. It may also be associated with thrombotic complications observed in many patients with COVID-10 (primarily embolisms caused by a blood clot blocking an artery in the lungs), as well as breakaway blood clots leading to unexpected stroke in some young and middle-aged adults.

There is more. The U.S. and several European countries have reported rare cases of a pediatric inflammatory disorder that shares features of Kawasaki disease (KD) and may be linked to the virus.

Described in our May 6 blog, KD is a very rare acute vascular inflammation almost exclusively affecting children. The prognosis is generally good, but the condition is clearly still a serious threat. One of KD’s most severe complications is coronary artery aneurysm. Although the cause of KD remains unclear, researchers hypothesize that a viral trigger may play a role in some genetically susceptible children because KD is associated with some viral respiratory infections, including seasonal coronavirus.

The annual incidence of KD is highest in Japan, at more than 300 per 100,000 children under the age of 4, compared with 25 per 100,000 children under age 5 in the U.S. Now some recent reports indicate a link between KD with SARS-CoV-2. In particular, a recent study published in The Lancet shows that the ongoing COVID-19 epidemic in Italy resulted in an increased monthly KD incidence at least 30 times greater than the monthly incidence of the previous five years. Moreover, there was a clear starting point after the first case of COVID-19 was diagnosed in North Italy. Similar observations were made in France, in the UK and now also in the U.S.

But let’s be clear. Although we need to pay attention to these findings, it does not change the fact that KD is a very rare condition, and the vast majority of children experience very mild COVID-19 symptoms when they are infected.

So, what does COVID-19’s growing list of apparent complications mean?

It means we are still at the beginning of our journey to fully understand the physiological effects of this vexing virus. And, it emphasizes the distinctiveness of a new respiratory virus that can ravage many parts of the body — and why we must persist in protecting ourselves.

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

To view Dr. Brechot’s recent interview with Rolling Stone, Click Here. He discusses the origins of COVID-19, and how the virology and wider scientific communities are working together for solutions.

May 13, 2020

Q & A: What you need to know about COVID-19

We have now entered the era of “containment relaxation.” This is a new chapter, an unprecedented situation. Two months have passed since we launched this blog, so let’s sum up some top public concerns and questions about COVID-19 in everyday life. Throughout our busy work and study days, we are bombarded with countless pieces of information about the new coronavirus, many of which are unconfirmed.

Clearly, many mysteries about COVID-19 remain. Yet, the one thing confirmed by all studies is that effective prevention of COVID-19 transmission should be based upon well-known public health measures: wearing a mask as soon as you leave your house, washing your hands frequently with soap and hydroalcoholic solutions, and respecting the social distance of at least six feet. This is key!

1. How is COVID-19 transmitted? Will I get infected if I go grocery shopping?

The predominant routes for human-to-human COVID-19 transmission are through respiratory droplets (from coughing, sneezing, talking) or by fomites: i.e., touching a surface or object contaminated by an infected person and then touching your nose, mouth or eyes. It is important to keep a social distance while at the grocery store. You must wear your mask. You should make a list of things that you need for at least a week or two. If possible, only one household member should go shopping to minimize unnecessary exposure. Before entering the home, try to leave your shoes outside and make sure all the products are thoroughly cleaned and disinfected. If possible, use gloves but make sure to minimize cross-contamination. Most importantly, don’t forget to wash your hands before touching anything in the house. You can clean and disinfect households as recommended by the Centers for Disease Control and Prevention.

2. Is a vaccine available?

Testing of vaccine candidates continues globally but, unfortunately, no vaccine is available yet. We have to wait. Safety is the primary goal for seeking approved vaccines. Many researchers have stepped up to develop vaccines against COVID-19. According to a recent published perspective in Science, new manufacturing platforms, structure-based antigen design, computational biology, protein engineering, and gene synthesis now provide tools for making vaccines quickly and precisely. The Global Virus Network recently published a scientific column about COVID-19 vaccines; please read it here.

3. Has the U.S. Food and Drug Administration (FDA) approved any drug to treat COVID-19?

A huge worldwide effort is focused on developing treatments to fight COVID-19 on many fronts. Several are very interesting candidates, including for preventive therapy. Yet, at this stage, the FDA has yet to approve any drugs to treat COVID-19. However, the agency created a Coronavirus Treatment Acceleration Program to speed up the development of treatments. For example, on May 1, 2020, the FDA issued an emergency use authorization (EUA) allowing the investigative antiviral drug remdesivir to be used in treating suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. However, the effectiveness of this drug must be confirmed. In addition, new immunomodulatory molecules have shown a lot of promise for combatting the acute respiratory syndrome, which affects about 5 to 10% of patients with COVID-19-related disease.

4. I keep hearing that the U.S. doesn’t do enough testing? Why?

At this point, we all know the importance of viral RNA testing and antibody testing. The main reason we do not conduct enough tests is that the supply of resources required for testing, including the swabs, reagents, and personal protective equipment, is still far below the demand. In addition, some people are reluctant to get tested because they fear discrimination associated with COVID-19. When capacity is sufficient to test for SARS-CoV-2 antibodies, such testing will help reveal the true scale of the population already exposed to the virus (particularly who experienced no or mild symptoms). Moreover, diagnostic testing for viral RNA should be mandatory. If you have been exposed to a confirmed case or experience any of the listed symptoms, please call your health care provider or county health department to schedule a test.

5. Should I stop seeing my doctors about my underlying health conditions during the pandemic?

No, you should keep up with all routine doctor appointments, including annual examinations. Most health care providers are available through telemedicine or are developing this technology to accommodate standard doctor appointments. Please check with your health care provider about what they can do for you. If you are a USF Health patient, please review this page for detailed information.

6. If I have recovered from COVID-19, can I be re-infected? How long does immunity last?

The presence of antibodies to COVID-19 does reflect elimination of the virus and protection, at least for most patients. But is too early to tell how long protective immunity may last. The levels of neutralizing antibodies from recovered COVID-19 patients vary from case to case. According to the World Health Organization, detection of antibodies suggested by some governments as a basis for an “immunity passport” does not guarantee protection against COVID-19 re-infection. Additionally, a viewpoint from JAMA Network suggests that the “immunity passport“ needs to be implemented with caution.

7. The weather is getting warmer. Is there any correlation between COVID-19 infection rate/mortality and weather?

According to several papers, including one recently published paper in Science of The Total Environment, the average temperature in each country negatively correlated with the number of SARS-COV-2 infections. However, no significant association was found between COVID-19 mortality and temperature. In fact, humidity seems to be a more important parameter. In the laboratory, the virus showed sensitivity to temperature. However, it is too early to predict whether seasonal changes will really affect the outcome of COVID-19 epidemics. More data are needed to draw reliable conclusions.

8. Are my pets safe?

Some SARS-CoV-2 cases have been confirmed in pet cats and dogs in Hong Kong and the U.S. However, not enough evidence exists to show that your pets can transmit the virus to you. If you are sick, limit your contact with your pets. If you suspect your pet is infected with COVID-19, consult your veterinarian. Here is a resource for COVID-19 in animals.

9. How can I maintain a healthy relationship with my family or other household members?

It is very challenging to work and live at home every day especially if your roommate, children and/or significant other are present at the same time. Here are some tips from Johns Hopkins University to help improve your relationship during this pandemic. Keep in mind that mental health problems should not be trivialized. When you need help, don’t wait.

10. When will it be over?

Of course, the sooner the better. But without a vaccine and/or therapeutic treatments, it is difficult to predict when this pandemic will end or possibly recur. All we can do is maintain our role as good citizens— be diligent about social distancing and personal hygiene. One day, we will emerge from this global health crisis and look back proudly at what we have done together to curb COVID-19.

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

May 6, 2020

Children and COVID-19: How infectious are they?

How many children have been infected with SARS-CoV-2? Are they contagious? Which treatments should we contemplate for them? These are all key questions to answer if we want to successfully implement our public health strategies in the coming months. Unfortunately, more studies are required to provide the information we need.

To date, the pediatric population accounts for only 1 to 5 percent of the reported infected patients worldwide. In most cases, the course of the disease is much milder in children than in adults. A few newborns have been infected, but the evidence for intrauterine transmission from mother to fetus is so far scarce. Kawasaki disease, a rare but serious inflammatory vascular disorder, has been potentially linked to COVID-19 in some children in the UK and in France. Such reported cases of this syndrome are unusual, but they indicate the need for caution and continued investigation.

What about children’s capacity to spread the virus, not only to other children but also to their parents and more vulnerable grandparents? While still controversial, most studies to date emphasize a lower viral load (amount of virus in the blood) and low transmission rates in children. Yet, a recent study from Germany suggests that the viral loads for children can be comparable to those seen in adults — but does this mean that children show the same potential for transmitting the virus? Fortunately, the answer appears to be no. In fact, the virus can be more easily transmitted from adults to children than from children to adults. This points to the complexity of viral transmission, which does not depend solely on the viral load.

Overall, growing evidence indicates that children yield less impact than adult populations in disseminating COVID-19 infection. This is key information for making decisions about sending the kids back to school. Again, we still need much more information about the impact of the new coronavirus on children – and hope to soon see some comprehensive studies on this topic in the U.S. and in Florida.

What can we expect when countries reopen?

After several months of battling the COVID-19 virus, at least 12 countries are preparing to reopen or lift some restrictions in certain parts of their countries. Florida was among the states in the U.S. to begin a phase 1 reopening this week. In New York, the epicenter for COVID-19, as the weather warmed up, many people rushed to parks over the weekend to breathe fresh air, the New York Times reported. You may wonder: Does reopening put more people at risk? Will the curve continue to flatten, or will we experience a second wave?

Without sufficient data, it is too early to draw conclusions. While many questions remain uncertain or unanswered, people’s lives here will slowly return to normal, as they have been in China. In the process, the following strategies and measures should be taken into account.

Increase testing capacity and volume

As emphasized many times in our previous posts, testing-identifying-tracing-isolating, testing and more testing are vital. Extensive tests (both for viral RNA and antibodies to the virus) are needed to reveal the true scale of this pandemic. Many diagnostic kits are now provided by various companies. We need to evaluate them carefully and standardize the results nationally and internationally. The University of South Florida is leading efforts to develop novel test kits and test the residents in our community.

Enhance and improve contact tracing

Contact tracing identifies and follow ups with individuals who may have been in contact with confirmed COVID-19 cases during the time when those patients were infectious. The Centers for Disease Control and Prevention advises contacts to stay home and to maintain social distance from others until 14 days after their last exposure in case they also become ill. Contact tracing is critical in fighting COVID-19 and other infectious diseases, such as Ebola. Based on a recently published article in the journal Lancet, isolation and contact tracing can reduce the spread of infection within the community. However, contact tracing is labor intensive and can be greatly enhanced by innovative technologies, such as smart phone/device applications.

The GPS and Bluetooth functions built into most people’s smartphones can be used to track contacts. Many countries, including China, Singapore and Australia, rely heavily on smartphone tracing apps to prevent COVID-19 from spreading further in their regions. Last week, Apple and Googlereleased virus contact tracing tools to public health organizations so agencies can build and test their own apps.

An editorial in Nature points out many challenges of relying on the smart phone apps for contact tracing. First, no global standards exist among different countries. Moreover, many users will question whether their data is stored safely, and whether the privacy of app users sharing the information is effectively protected. The contact tracing app sends you an alert when you are in close contact with a confirmed case. Based on the data received and your social circle, the infected individual who is supposed to remain anonymous may be easy to identify. An original investigation published in JAMA Internal Medicine suggests that the maximum benefit from contact tracing can be achieved only while following other measures such as testing and social distancing.

Maintain protective measures

As we try to strike a balance between protecting ourselves and restoring our lives, keep some principles in mind. First, a recent journal article in Mathematical Biosciences, reports that early termination of social distancing may trigger a second wave of COVID-19. So, wearing face masks and maintaining social distancing practices are highly recommended, and these measures will be the new normal until a vaccine is eventually available. Secondly, everyone must continue to practice good personal hygiene: wash your hands frequently, avoid touching your face, and cover your mouth when coughing or sneezing. Lastly, remain positive and safely maintain daily physical activities. Physical and mental health are equally important during this time. Remember, we are all in this together, and we will fight this pandemic together.

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

April 29, 2020

Basic research meets epidemiology: Can nicotine patches prevent SARS-CoV-2 infection?

Let’s be clear: this is still a hypothesis. But a great paper recently published by the French National Academy of Science proposes, with substantial rationale, that controlled nicotinic agents may efficiently prevent or control infection by the COVID-19 virus. Here’s how that might work:

We know that SARS-CoV-2, like other human coronaviruses (SARS-CoV-1, MERS-CoV) and some animal coronaviruses), infects the central nervous system (CNS). In fact, several clinical observations indicate that patients with COVID-19 experience neurological dysfunction, and this may play a role in the respiratory failure of some. Moreover, loss of the sense of taste and/or smell (anosmia) is quite frequently observed and might even correlate to the severity of the infection. Those with anosmia may possibly experience less severe courses of infection, but this needs to be confirmed.

We have also learned that SARS-CoV-2, such as several other viruses including coronaviruses, enters the olfactory epithelium and progresses into the brain to the olfactory bulbs. But how does the virus enter neural (nerve) cells? It has been well established that angiotensin converting enzyme II (ACEII), acting synergistically with a cellular serine protease (TRMPSS2), is a major receptor used by the virus to enter targeted cells. But could the virus enter through additional receptors?

This is where serendipity, or “open thinking,” comes into play. Scientists have long known that the rabies virus infects neurons by binding its envelope protein to the nicotinic acetylcholine receptor (nAChR). In fact, nAChR plays a critical role in the host-pathogen interaction by down-regulating inflammation (the so-called cholinergic anti-inflammatory pathway), and the rabies envelope inhibits nAChR activity. So, the virus not only uses the receptor to enter the brain; it also inhibits the receptor’s anti-inflammatory potential. These nicotinic receptors are also present in cells lining the interior surface of blood vessels in the lungs (lung epithelium).

A nicotinic treatment might compete with the viral envelope for binding to the nAChR, decrease entry of the virus, and partially restore the anti-inflammatory activity of the receptor. Why?

That’s where basic research and structural biology come in. A study was conducted based on very sophisticated electron microscopy (cryo-EM) of the SARS-CoV-2 spike (S) protein, the envelope protein that binds to the cell surface. The advanced microcopy demonstrated that SARS-CoV-2 and rabies viral envelopes share similarities. Thus, SARS-CoV-2 might also bind to the nicotinic receptor to enter cells and block nAChR.

Now, add epidemiology and clinical observations to that structural biology discovery. Recent solid evidence indicates that the COVID-19 rate among smokers is less than that of nonsmokers — even after taking into account potential confounding factors of smoking, such as age and sex.

Overall, epidemiological, clinical and basic research evidence suggests that Covid-19 infection may be prevented and controlled by nicotine. With this in mind, French clinicians have begun testing whether COVID-19 can be effectively treated by administering nicotine through skin patches, or other methods like nasal spray or chewing gum. Let’s wait and see, but, if successful, this bold and simple approach would be quite a breakthrough!

At the same time, infected individuals who smoke have a worse prognosis than those who do not. So let’s be clear. This new COVID-19 clinical research evaluating nicotine substitutes — which contain small amounts of nicotine without other harmful chemicals found in tobacco — is not an encouragement to smoke.

COVID-19 antibody therapy: convalescent plasma transfusions

While we wait for clear COVID-19 drugs or a vaccine to provide widespread immunity, the population is still vulnerable. In the meantime, many researchers and health care providers are leaning towards the historical, experimental treatment commonly called “convalescent plasma.”

What is convalescent plasma?

Plasma makes up 55% of your blood in the form of liquid. The rest is comprised of red blood cells, whites blood cells, and platelets. Plasma contains immune-boosting antibodies that help your body fight off viruses, bacteria and other pathogens. Convalescent plasma (CP) is a post-infection potential therapy identified for viral diseases. The treatment collects plasma containing antibodies from the blood of recovered COVI-19 patients (donors) and then transfuses those potentially antibodies into infected patients to neutralize the virus. The purpose, when no other treatment or vaccine exists, is to improve survival rates.

CP therapy is not a new concept and can be traced back to a century ago. Its effectiveness was evident during the outbreak of H1N1 virus in 1918, SARS in 2003, as well as in the H1N1 pandemic in 2009. Most recently, it was used to treat Middle East Respiratory Syndrome and Ebolapatients.

Physicians from many countries, including India, China, South Korea, Italy and the U.S are all enthusiastic about using CP therapy to help severely ill COVID-19 patients recover more rapidly. The MayoClinic, working with 56 other institutions, leads the U.S. project investigating this antibody therapy for hospitalized patients with severe or life-threatening COVID-19, or those at high risk of serious disease progression. The U.S. Food and Drug Administration has published recommendations for using COVID-19 CP in clinical trials and for emergency purposes.

Promising early results, but challenges remain

Apreliminary communicationon JAMA Network reports an uncontrolled case series in which the clinical status of five severely ill COVID-19 patients improved after they received CP therapy. A study published in the Journal of Medical Virology demonstrates a similar finding.

As promising as CP therapy may be, many challenges lie ahead in proving its effectiveness.

First, the FDA recommends that patients with severe or immediately life-threatening disease meet criteria for the use of COVID-19 CP therapy, but the optimal dosage and timing of the therapy remains unclear. That will be important to know, because CP transfusions carry the risk of a damaging immune reaction. Instead of being defended against the virus, patients could suffer a “cytokine storm” driven by inflammation in overdrive. A studyreporting on CP therapy for H1N1 influenza, suggested that a single dose of CP with neutralizing antibodies titers of greater than 1:160 effectively reduced mortality and the respiratory viral load..

Secondly, although COVID-19 positive cases now surpass 3 million, not enough people qualify as CP donors. According to FDA guidelines, CP donors must completely recover from the COVID-19 infection and have undergone an initial positive diagnostic test. If a diagnostic test was not performed, then patients are required to obtain a positive antibody test. Before donating plasma, they must either be asymptomatic for 28 days, or be at least 14 days asymptomatic and have a negative diagnostic test. All CP donors must also meet minimum eligibility criteria to donate blood. All these requirements can exclude many potential donors.

Finally, tests are available to identify recovered patients with high levels of antibody response; however, standard guidelines for use of these antibody tests still must be developed.

Despite the challenges, CP is worth studying as a therapy that may limit the loss of life during this COVID-19 pandemic. Further published data is needed to prove its benefit.

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

April 22, 2020

Collaboration more important than ever to curb a pandemic characterized by uncertainties

The pandemic caused by SARS-CoV-2 is less than two months old, yet seems longer. Scientists face extraordinary challenges, particularly when it comes to balancing the understandable urgency of the public expectations for immediate research outcomes with the reality of science, which requires time to avoid mistakes, hasty conclusions and misleading announcements.

The discussion on antibody testing is a good illustration of this dilemma. We need widespread use of diagnostic kits as soon as possible, but must also standardize testing and choose the right kitsto obtain the best results (as mentioned in previous blogs). At the same time, we now face the reality of coronaviruses infections. Antibodies do not last very long, maybe a few months. Some neutralize (defend against) viral invaders – but others may facilitate adverse immune reactions, such as a subsequent infection.

Scientists are tackling the challenge of balancing the demand for rapid COVID-19 research outcomes with the need for accurate and clinically meaningful diagnostics and therapeutics.

To cope with these challenges, we need to organize prospective cohorts of patients infected with SARS-CoV-2, evaluating the outcomes of those treated with the investigational therapies, and those not treated. This is the only way to truly understand immunological responses to the virus, design robust vaccines, investigate the extent and effects of viral genetic variability, and evaluate the interplay between genetic variations and the genetic profile of infected patients. The scientific method takes time, and it won’t allow us to draw useful conclusions for this first round of epidemics. But, it is the way to get meaningful results.

Meanwhile, we must encourage transdisciplinary efforts to find rapid solutions as well as engage in the more long-term research efforts. This is exactly what the University of South Florida has initiated, and I am proud to participate with so many colleagues and friends. The task force launched by USF President Steve Currall and Senior Vice President Paul Sanberg has attracted many research ideas and proposals that will be extremely useful; USF Health clinical studies at Tampa General Hospital will facilitate prospective follow-up of patients with COVID-19; and the university’s partnership with the GlobalVirus Network will allow us to integrate the results in an international context.

While I have led many large and renowned research institutions, I’ve never witnessed such rapid mobilization as achieved both here at USF and by the entire international community. That’s why I remain optimistic that, beyond all the struggles and uncertainties, the overwhelming response to this pandemic will lead to meaningful discoveries in the fight against COVID-19 and future emerging infectious diseases.

Predictive models for COVID-19 are critical, but interpret with caution

As COVID-19 continues to spread worldwide, predictive models have increasingly drawn the attention of the news media and of policymakers. The Institute for Health Metrics and Evaluation (IHME) model has gained the most attention and generated debate in the U.S. In this blog, we will not attempt to evaluate which models are more valid, but to share how such mathematical models may be useful as the pandemic evolves.

What are predictive infectious disease models?

Predictive modeling uses available data and reasonable assumptions to predict how an infectious disease spreads in the real world. All models are simplifications of reality. Many different kinds of predictive models exist to simulate the outbreak. The most common is the Susceptible-Infectious-Recovered (SIR) predictive model. The population can be the host of disease (susceptible); infected by the disease and show symptoms (Infectious); or recovered or naturally immune from the disease (Recovered). The model demonstrates how individuals move from one stage to another. By adding populations who experience a long incubation period (Exposed), you get a more advanced model known as Susceptible-Exposed-Infectious-Recovered (SEIR). Using different variables and equations, the model can calculate when COVID-19 cases will peak under certain circumstances. Many parameters affect the accuracy of a predictive model.

Predictive modeling uses existing data and reasonable assumptions to forecast how an infectious disease spreads in the real world. As more data becomes available, it triggers adjustment of the model, resulting in different outcomes.

How can modeling help us?

A viewpoint recently published in JAMA indicates the primary purpose of predictive models is to assess the relative effect of interventions in reducing health care burden, rather than to forecast the exact number and duration of cases. Nevertheless, in early March, a paper based on the transmission of COVID-19 in Hubei, China, was published by a group of Chinese scholars. Their aim was to help the rest the world understand the predictability of virus spread and make proper decisions to help prevent or slow the outbreak. The predictive values of these models are only useful when compared under different intervention scenarios. For example, by computing the effects of different potential measures such as social distancing, wearing face masks or home isolation, the simulations can guide government leaders’ decisions during the pandemic. According to an article in Nature, many countries, like the U.K. and the U.S, are using the predictive models as their “wind indicator” to implement preventive infection control measures to curb the pandemic and to put in place certain economic policies to support their citizens.

What are the drawbacks of predictive modeling?

Improper estimation and prediction based on inadequate forecasting models will affect the resilience of the national health care system and could have adverse consequences. For instance, not every state or region implements social distancing the same way. Also, as more data becomes available daily, it triggers the adjustment of the predictive model, resulting in different outcomes. Moreover, infection rates, disease incubation period, case-fatality ratios, comorbidities, age distributions, and the correct number of asymptomatic individuals must be taken into account for the accuracy of projections. Unfortunately, during this current pandemic driven by a new virus, reliable data is very challenging to collect.

What course should we follow?

Based on the analysis report of Imperial College London’s model, a combination of mitigation measures, such as home isolation, home quarantine and social distancing, may reduce the peak medical demands by two-thirds and deaths by half. So far, the lockdowns in Europe and social distancing in the U.S. seems to be working as expected. However, the question remains: When these can these measures safely be lifted or relaxed? Will reopening certain areas lead to a second wave of COVID-19? Without standard COVID-19 drugs or other treatments, as well as the absence of a vaccine, the population is still vulnerable to COVID-19. Policymakers should exercise caution in relying solely on predictive models to make decisions about bringing people back to school and work, and resuming the normal activities of life. More data are needed for further actions.

Christian Bréchot, MD, PhD
Senior Associate Dean for Research in Global Affairs, USF Health Morsani College of Medicine
Associate Vice President for International Partnerships and Innovation, USF
Professor, Department of Internal Medicine
President, Global Virus Network

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

April 15, 2020

Importance of COVID-19 diagnostics and lessons for future pandemics

Diagnostic tests are at the heart of the fight against infectious diseases — something not fully appreciated by governments, national and international institutions, or venture funds (when it comes to financing biotech companies).

We need treatments and vaccines, but the key to containing a new pathogen that threatens the world is early detection of infected individuals and immediate contact tracing. This is exactly what has not happened for SARS-CoV-2 in most countries, with the notable exceptions of South Korea, Taiwan and Germany. Now, it is possible to use serology-based assays (antibody blood tests) to evaluate how extensively populations have been exposed to the virus, key information to help us figure out how to ease out of containment, return to a more normal life, reinvigorate the economy, and take care of patients who suffer from other diseases and cannot be properly treated in the present context. Indeed, dealing with a general population massively exposed to the virus (about 50-60%), a level that offers protection against a “second episode” of epidemics, differs from managing more limited population exposure (around 5-10%). Unfortunately, the more likely smaller exposure percentage can sustain the risk of reinfection upon containment relaxation. So, again, diagnostics will be at the heart of any strategy in the coming months.

COVID-19 nasal swab laboratory test

Before drawing shaky conclusions that could lead to another crisis, we should keep a few things in mind. First, a series of diagnostic tests have been proposed by biotechnology companies and academia. However, their sensitivity-specificity and reliability-reproducibility markedly differ, so we need standardization and thorough evaluation. This can be performed rapidly but must be done carefully, not only by national agencies but also at the international level. (The Global Virus Network will contribute to this assessment, incorporating its experience in 50 centers around the world.)

Secondly, an academic community cannot design diagnostic tests without the support of industry partners. The academic scholars can generate the concept, the bold and smart ideas, and this is how we make progress. But, then, industry must drive large-scale development – attaining a robust, easy-to-use test that can be massively produced and distributed. I see too many academics who believe they can do the entire job themselves.

Finally, how can we better prepare for future pandemics? The Coalition for Epidemics Preparedness Innovations (CEPI), set up after the Ebola crisis in 2014, has made real progress in developing standby vaccines against known viruses and in responding quickly to new ones, such as the current SARS-COV-2 virus. The creation of CEPI, a consortium of large foundations (Bill and Melinda Gates, Wellcome Trust), large pharmaceutical companies involved in vaccine development, the World Health Organization, the National Institutes of Health, governments, and other organizations, is clearly useful in preparing for prevention and treatment.

We should do the same for diagnostics, building upon the resources of existing institutions such as the Foundation for Innovative Diagnostics (FIND), based in Geneva and supported by the Bill and Melinda Gates and Wellcome Trust foundations. Only through close collaborations among academics, industrial partners, nonprofit foundations and research agencies can we outsmart our common invisible enemy, the viruses.

Psychological well-being during the COVID-19 pandemic

With the dramatic daily rise of COVID-19 cases, the rapidly emerging COVID-19 pandemic has affected our psychological well-being as well as physical health.

Over100 countries – representing one third of the world’s population — are either completely or partially locked down, according to the data. Escalating levels of anxiety, stress, sadness, anger, guilt, or post-traumatic stress are common during outbreaks, coinciding with daily reports of cases and deaths, quarantine and stay-at-home orders, overwhelming news coverage, and lack of social interaction caused by social distancing. In many countries, including China, Italy, the U.K. and the U.S., the mental health of frontline health workers is more fragile than ever as they struggle to balance the responsibilities of caring for patients, family, friends and, above all, themselves. Not surprisingly, health care groups that combated previous outbreaks of Ebola, H1N1, and 2003 SARS, experienced similar mood swings.

Based on recent psychiatry research, health care professionals working in intensive care units, emergency departments or infectious disease departments are twice as likely to suffer from anxiety or depression as those not directly exposed to COVID-19 patients. Due to the increase in cases and the shortage of resources, many medical staff members are severely overworked. As a result, they are under constant pressure to provide adequate care to patients without standard COVID-19 drugs or other treatments. They do this while enduring the loss of their patients and colleagues, fully realizing their risk of becoming infected or infecting others (including their own loved ones), and experiencing stigmatization as caregivers for COVID-19 patients.

A new study in Psychiatry Research reports that health care professionals in ICUs, emergency departments, and infectious diseases departments are twice as likely to suffer from anxiety or depression as those not directly exposed to COVID-19 patients.

Psychological intervention and prevention is critical to maintain the mental health of frontline healthcare professionals as well as the “health” of the medical system. We need to ensure that basic needs are met; for example, reasonable working hours, access to physical activities and healthy, balanced diets. Appropriate precautions such as personal protective equipment (PPE) should be taken. Furthermore, effective communication among health care team members, and tremendous support from leadership and family will help providers cope with the mental stress.

We must also address the mental well-being of other vulnerable groups, such as recovered COVID-19 patients, children, the elderly, pregnant women, the Asian population (a special case in this pandemic), and last, but not least, frontline COVID-19 workers, including first responders, cashiers, gas station attendants, restaurant workers, and delivery personnel. Take children, for example; most don’t understand why they can no longer go to school or gather with friends for social activities. Many schools in different countries have implemented virtual classrooms, resulting in more screen time and less physical activity. Adults need to set good examples to guide children in their lives through the stressful time of home confinement.

During this pandemic, the general public should remain aware of potential psychological reactions, maintain a positive attitude, be selective in determining what information to rely upon, take preventive measures to protect themselves and others from infection, and use online networks or cell phones to reach out to family members and the community. Most importantly, seek appropriate help when needed, through telemedicine and social support resources.

In short, collective and individual psychological effects can last long after the outbreak ceases. The emotional well-being of health care professionals and entire communities must be addressed both during and after any disaster, including pandemics. Appropriate approaches should be implemented to overcome the impact of psychological distress on various target groups.

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

April 8, 2020

Vaccine development challenges and the debate over masks

When and how will a vaccine to prevent COVID-19 happen?

As the SARS-CoV-2 pandemic continues, we already must think about the possibility that the virus may “return” next year and in the future. That means we must meet the urgent need for safe vaccines to protect against COVID-19 – and that takes time. Some phase I clinical trials to assess the tolerance of vaccine candidates in healthy individuals have already started. Several companies are even planning phase 2 trials with larger groups of people to determine effectiveness and further evaluate safety. Finally, phase 3 studies will test whether the vaccine works well in a “real world” context. So, we may have to wait 15 to 18 months for a vaccine ready for widespread use – and that estimate encompasses a very fast track record. Several scientists, including myself, co-signed a letter urging regulatory agencies to shorten the process. We will see.

What are some coronavirus vaccine approaches being tested?

At least 30 companies and academic groups are working on various approaches, and the competition has already shown promise. To induce an immune response, some vaccine platforms use direct injection of mRNA encoding for the viral proteins, in particular those shaping the “spikes” of the coronavirus. Others deploy viral vectors — such as measles, lentiviruses, adenoviruses or others — to carry a synthesized fragment of SARS-CoV-2 encoding the coronavirus spike protein for expression in the cell and presentation to the immune system. Finally, other groups work directly with viral peptide sequences chosen from structural analyses-derived studies and then injected into consenting study participants.

What will be the criteria for success?

First, let’s not forget that no one has yet successfully developed an efficient vaccine against a human coronavirus. We have no vaccines against SARS-CoV-1 or MERS-CoV. The major challenges to address include:

–Should we rely solely on generating a humoral immune response, indicated by the appearance of antibodies to specific viral proteins, or should we also rely on a cellular immune response in which T-cells (a type of immune cell) destroys infected cells? We know that COVID-19 produces protective antibodies, including neutralizing antibodies that block infection, but for how long? What is the real proportion of patients who get such neutralizing antibodies? The capacity of a vaccine to generate cellular immune response will likely be very important.

–What is the impact of the viral genetic variability? Should we worry that certain variants will “escape” from the vaccines we are preparing now? We really don’t know. So far (see our April 1 blog), no evidence exists for such evolution of the virus, but we should remain prudent.

–Would attempts to prepare vaccines with a “common core component” for all coronaviruses, be feasible?

Overall, these challenges imply that, concurrent with vaccine development, we must extensively analyze the immunological parameters during carefully designed follow-up of patients with COVID-19. We need to speed up carefully and spend time evaluating investigational vaccines in animal models. These models only partially recapitulate what happens in humans, but at least we minimize the risks. This would be particularly relevant to rule out inducing harmful “antibody dependent enhancement.” This is a phenomenon (as described for the dengue fever virus, for example) in which antibodies generated by the first infection do not protect against the virus, but actually enhance the second infection.

Can we identify other paths to eradicate COVID-19?

An interesting, complementary approach for vaccines recently emerged. Several studies reveal that some live vaccines, such as those administered for measles, bacillus Calmette-Guérin (BCG), pertussis and other diseases, produce pronounced nonspecific protective effects, while inactivated (or killed pathogen) vaccines do not. In fact, some strains of BCG vaccine not only confer protection against disseminated forms of tuberculosis, but also induce immunity against infections caused by nonrelated pathogens. Along these lines, a highly provocative new study found that countries without universal policies of BCG vaccination (Italy, the Netherlands, U.S.) have been more severely affected by SARS-CoV-2 than countries with universal and longstanding BCG policies. The authors also argue that BCG vaccination reduced the number of reported COVID-19 cases in a country. Related hypotheses have been proposed about the capacity of oral polio vaccines to stimulate such “cross-protection.” Can we take advantage of such bold approaches? We must be cautious, but this also needs to be explored. Ultimately, only extensive international cooperation and more flexible intellectual property and regulatory regulations will allow us to rapidly embrace so many scientific and development challenges.

How is the COVID-19 virus transmitted?

A recent World Health Organization scientific briefing, reported that the predominant route for COVID-19 transmission is human to human through respiratory particles known as droplets (>5-10 μm), which are emitted during sneezing or coughing. The second mode of transmission is through direct contact: transfer of the viral pathogen from a contaminated surface/environment to the mouth, nose or eyes. What worries us most is a potential third mode of transmission — that aerosolized viral particles may be spread through the air by talking, or even normal breathing.

Recent correspondence from the New England Journal of Medicine noted that the virus remained in aerosols as the infection titer decreased throughout a three-hour experiment. Also, the 7^th version of the guidelines for diagnosis and treatment of COVID-19 in China indicates that especially in relatively closed environments (such as elevators and stairwells), the virus may spread with prolonged exposure to high concentrations of viral particles suspended in air. Conversely, another study from Singapore, found no transmission through aerosol had been reported. Since we lack efficient research and valid data, it’s still debatable whether the COVID-19 virus can be spread by aerosol.

So, should a face mask be used?

According to a review in The Lancet, after the outbreak of SARS-CoV-2, many countries implemented their own recommendations about the use of face masks. In countries like China and Japan, wearing face masks in public has become a daily routine to stop transmission of the virus. Last week, the U.S. Centers for Disease Control and Prevention also issued recommendations for wearing cloth masks in public areas. People may still be unclear about the need for and effectiveness of the measure.

Keep in mind that the most effective way to contain a pandemic is not to cure all the sick patients, but to stop the spread of the infection. Without cutting off the source of transmission, anyone in the community can become infected to the extent that no health system in the world can absorb all the cases.

When should a mask be worn?

A recent study in Nature Medicine concluded that surgical face masks can prevent transmission of human coronaviruses and influenza viruses from both larger respiratory droplets and aerosol exhaled by symptomatic individuals. More studies are needed to determine whether this also applies to COVID-19 but, in the absence of treatments or a vaccine, wearing a mask during this pandemic should be a universal precaution. Masks should especially be worn in public, because a yet unidentified asymptomatic population of SARS-CoV-2 infected patients has the potential to shed the virus.

N95 respirators are designed to block 95% of small particles (0.3 micron), including airborne particles, when properly fitted to the face. They are commonly used in industrial or health care settings and are not recommended for use by the general public. Surgical masks are disposable and can block large droplets from sneezing, coughing, or talking. They should be worn by people with COVID-19 related symptoms to prevent spreading infection to healthy people. However, used surgical masks must be properly disposed; otherwise, they pose a potential health hazard for others.

Cloth masks, which can be made at home, washed regularly and reused, are suitable for people showing no symptoms to wear in public. Their widespread use is a good way to slow the asymptomatic population from unknowingly infecting others.

It is vital to ensure that those at high risk – health care providers, nursing home workers, sick patients and the people caring for them — have an adequate supply of N95 respirators and surgical masks. There is no need for the general public to hoard these types of masks.

In summary, a face mask of any kind can only help reduce the risk of infection. These coverings will not make you invincible against the virus. Nor are they an alternative to washing your hands or following appropriate physical distancing measures. For optimal prevention, wear your masks in public areas, maintain good hand hygiene, and keep a safe physical distance.

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

April 1, 2020

Antibody tests: The only reliable approach to reveal true scale of the SARS-CoV-2 pandemic

While we were preparing this week’s blog, the U.S. surpassed China and Italy as the worldwide leader in confirmed coronavirus cases. New York, for example, became the new epicenter of the current pandemic as the number of confirmed cases surged each day.

What is COVID-19 testing?

According to World Health Organization, when a patient meets the suspect case criteria, upper and/or lower respiratory tract specimens, such as a nasal or throat swab, sputum, and/or endotracheal aspirate, should be collected from the suspected cases and screened for the virus. They are screened using a nucleic acid amplification test (NAAT), such as real-time reverse transcription-polymerase chain reaction (rRT-PCR). This molecular technology converts the specimen’s RNA into DNA, which is rapidly amplified to detect tiny genetic pieces of the virus. If genetic material of pathogen SARS-CoV-2 is present, the patient is diagnosed with COVID-19.

Rapid diagnostic tests have been needed to decentralize testing capacity and help make up for lags in current testing. Now, we will have the possibility to perform rapid testing, with results being available in around 5 to 10 minutes. The specificity of these tests still must be evaluated, but this is real progress.

However, the real question now, in addition to increasing NAAT test capacity, is does NAAT provide enough data to help reach the ultimate goal of curbing this pandemic? We expect the best epidemiological data yet to be provided by upcoming antibody blood tests.

What is an antibody test?

Unlike the current tests collected primarily by nose or throat swab, the antibody test (known as a serological assay) relies on drawn blood. This blood test detects whether people have developed antibodies, molecules made by the immune system to attack disease-causing organisms (pathogens) and the level of antibodies in their blood. Many countries including France, the Netherlands, UK, Germany, China, and Singapore, as well as certain states in the U.S., are working rapidly to produce and promote the test, which can provide a bigger picture of populations infected and the full scope of immunity to COVID-19 within communities.

Dr. Florian Krammer, professor of microbiology at the Icahn School of Medicine at Mount Sinai in New York City, a center affiliated with the Global Virus Network (GVN), developed a similar test: the serological enzyme-linked immunosorbent assay (ELISA) test. According to the medRxiv preprint, the assay was created using recombinant antigen extracted from the spike protein (S protein) of SARS-CoV-2. The S protein conveys the virus to receptors on the host cell surface and helps the virus invade the human cell where it replicates. When infected with COVID-19, the body produces antibodies that recognize the “foreign” S protein and destroy the virus.

What is the difference between NAAT and the serological assay test?

While NAAT checks whether someone is currently infected, a serological assay identifies whether an individual has been infected in the past and if their immune system mounted an antibody response to the virus. It can identify even asymptomatic people (those who were infected without showing any apparent symptoms) — a mystery yet to be solved in this pandemic.

The antibody test offers several other advantages: it can demonstrate the true prevalence of SARS-CoV-2 infection within the population, and it’s simple and affordable. Blood from a finger prick is sufficient to generate the test result.

Most countries are implementing social distancing to flatten the pandemic’s curve. At some point, the population will need to resume normal life. Large-scale antibody testing can help officials determine when it’s safe to limit social distancing and allow people to return to work and public activities. In particular, the test can help determine which frontline health care providers were infected and developed immunity to the virus, so they can continue fighting the virus without endangering patients or their health.

Finally, antibody tests can identify recovered patients with high levels of antibody response. The antibodies in their blood can be harnessed through “convalescent plasma” to potentially treat patients with severe COVID-19. This investigational treatment may lead to the end of the pandemic, but further research is needed.

The tests have limits. Negative antibody test results cannot rule out infection with COVID-19 since immunity typically occurs after a few days of infection. Furthermore, NAAT testing is required to confirm the infection. Little data exists on how long antibody-mediated immunity lasts. Last, but not least, the reliability of the test must be proven. How do we know that patients are not responding to other kinds of coronavirus? Are laboratories in different countries using the same standard to design the antibody test and evaluate its results? Standard protocols need to be developedand are currently being assessed, in particular by the Foundation for Innovative New Diagnostics (FIND) jointly supported by WHO and the Bill and Melinda Gates Foundation. Future research and clinical trials must support the use of antibody blood tests.

Why are there big differences in mortality rates for this new coronavirus from one country to another; what is the contribution of virus genetic variability?

Keep in mind that we do not know the actual mortality rates of COVID-19, because the number of all infected individuals is still unknown. Yet, the number of confirmed deaths do seem to vary widely among countries, ranging from 0.7% in Germany to as much as 10% in Italy and Spain. We do not precisely know why — but clearly, the age of infected populations and testing strategies are key. SARS-CoV-2 appears to have targeted a group of young adults in Germany (in particular contaminated when skiing) versus an elderly population in Italy. Moreover, Germany immediately recognized the need to test individuals with mild symptoms and their contacts, not just focus on those with pneumonia.

Are some genetic variants of SARS-CoV-2 associated with higher mortality?

We do not know for sure, but this is emerging as an important issue to solve. Keep in mind that any virus, especially an RNA virus, generates a large number of genetic variations, or mutations, when multiplying due to “errors” in replication of the viral RNA polymerase. Moreover, such mutations can induce selective advantage or disadvantage to the virus and thus be selected or counter-selected as a result of natural evolution of the infection – but also in response to treatments and/or containment measures.

So, mutations will be detected. The more pertinent question is how relevant are they are to the clinical, virological and biological patterns of the COVID-19? The impact of the mutations will depend on which viral genes are affected by the mutations. For instance, changes in the “spike” encoding proteins may influence how the virus binds to its cellular receptor and, therefore, the type of cells infected by the virus (known as cellular tropism). Mutations in the viral polymerase may change the level of viral multiplication, while other mutations in viral proteins might affect immune response to the virus.

We are still at the early stages of this global pandemic, but the overall genetic variability of the virus seems low. If this holds true, it may markedly benefit the effectiveness of treatments and the future success of vaccines.

Two intriguing studies from China – one an accepted paper and the second a preprint – are based on variations in functional sites of the receptor-binding domain (the spike viral proteins). The researchers suggest that at least two major forms of the virus have been circulating. These two “genotypes” are very closely related. One study refers to the two genotypes as “Types I and II” and the other study refers to the “S and L” forms. The researchers suggest that L (or Type II) was more prevalent during the burst of the aggressive epidemics in Wuhan, while the S (or Type I) form induces less severe infection and may spread more quickly worldwide. This observation may help explain severity of the COVID-19.

But, even more provocative, the researchers hypothesize that the S strain might have preexisted in China in humans before the epidemics were identified and that the more recent L strain appeared through mutations and selection of the variant. If confirmed, this observation might also have a big impact on vaccination-based strategies. It raises the theoretical possibility of antibody-dependent enhancement whereby (as with dengue fever) antibodies to the virus induced by the first infection would not protect against a second infection, but actually make it worse. This hypothesis has already been brought up for other coronaviruses, such as MERS-CoV. In any case, some GVN members have emphasized the need for prudence before vaccinating the general population.

Other studies have described mutations in other regions of the SARS-CoV-2 genome, particularly in genes affecting the structure of the viral particles. Observations from GVN centers in Italy indicate the presence of mutations in the viral RNA polymerase that may lead to increased rates of viral replication.

All these observations still need to be proven. As we read the research literature on COVID-19, it is important to remember the evidence we still need — mutations in cultured cells to demonstrate their effect on viral multiplication and good, methodical clinical studies to determine if and how the mutations affect humans. This will only be achieved through international collaboration, data sharing, and the simultaneous study of host and viral genomes.

Christian Brechot, MD, PhD
Senior Associate Dean for Research in Global Affairs, USF Health Morsani College of Medicine
Associate Vice President for International Partnerships and Innovation, USF
Professor, Department of Internal Medicine
President, Global Virus Network

Linman Li, MBA, MPH, PMP, CPH
Associate Director, USF Medicine International
USF Health Morsani College of Medicine
Vice President, Global Virus Network

March 25, 2020

“Invulnerable” young adults not only contribute to pandemic’s spread; substantial numbers suffer respiratory distress

As of March 24, over 375,000 coronavirus cases and more than 16,300 deaths were reported from 196 countries, according to the World Health Organization. Last week, China reported no new cases from Wuhan, the epicenter of the outbreak. In contrast, Italy had exceeded the total number of deaths in China. It has been clear from the beginning of this pandemic that the death rate increases very significantly in old and fragile individuals. This led many to consider that young infected patients are primarily “carriers” of the virus, contributing only to transmission of the infection and suffering few ill effects themselves.

Many young adults still believe that they are invulnerable or even immune to the virus (currently no vaccine against the respiratory illness COVID-19 exists), and they tend to ignore social isolation or physical distancing. But a more disturbing reality is emerging as the pandemic evolves; a significant number of infected young persons have been hospitalized for respiratory distress, including many requiring critical care in ICUs.

Indeed, the most recent Epidemiology Report from Australian Government Department of Health indicates that the highest proportion of the country’s 295 confirmed coronavirus cases affect people ages 20 to 49. Also, 47.5% of hospitalized patients in Australia are people ages 20 to 49. In Italy, 50% of those hospitalized in ICUs were younger than age 50 – and in France as well. Similarly, in the U.S. more than half of all confirmed cases in New York are in people younger than age 49.

The most recent study from the U.S Centers for Disease Control and Prevention shows that about 20% of hospitalized patients are ages 20 to 44. Although the study has limitations, such as not identifying whether these young patients had underlying conditions, the risk of getting sick or even dying should be highly considered by all ages.

Some may argue that the chance of otherwise healthy young adults developing severe symptoms is still relatively low — but is this a risk young adults are willing to take? Even if they are unconcerned about their own susceptibility, it’s important for young people to recognize that this highly contagious respiratory virus can infect anyone and even those without apparent symptoms can accelerate its spread to family, friends or others. Ignorance of social distancing puts other vulnerable groups at risk. This pandemic has become the touchstone to test individuals’ values, principles and social responsibilities. We’re all in this together, so let’s all stay socially isolated to protect the medically vulnerable, help limit disease spread and reduce the strain on our health care system.

An all-out scientific push to find drugs and a preventive vaccine to treat SARS-CoV-2

No current treatment specifically targets this new coronavirus, SARS-CoV-2, or the closely related SARS-CoV-1 virus. We remain hopeful that the huge drug discovery effort underway will lead to new compounds. However, given the time required to develop safe and effective new drugs, such compounds will not be available in time to curb the present pandemic. Also, despite fantastic work being done to design vaccines against SARS-CoV-2, this form of immunotherapy will, at best, take around 18 months to become available. In fact, several scientists with the Global Virus Network have pledged to take the time needed to evaluate any promising vaccine candidates in animal models before vaccinating humans. This preclinical testing is critical to avoid severe vaccine side effects, such as those encountered with dengue virus – namely, the generation of antibody-dependent enhancement that can lead to increased infection. In this context, repurposing drugspreviously FDA-approved for other diseases or pathogens is our best chance.

Here’s the good news. We can use existing antiviral drugs that directly inhibit the replication machinery of the virus, such as remdesivir, faviparavir, lopinavir, or others. Several of these have been used to treat HIV. Some limited studies suggest that remdesivir works in COVID-19 patients with severe respiratory distress.

We can also investigate new uses for old drugs that target infected human cells, limiting the ability of the virus to enter and replicate in the cells. Chloroquine and its derivative hydroxychloroquine – extensively used in the past to treat malaria – are at the forefront of this class of molecule. Several small studies point to chloroquine’s effectiveness in reducing the concentration of viral particles (viral load) and how long the virus stays in the bloodstream (viremia) – both key to controlling the disease and the pandemic. One highly referenced, but very small, French clinical trialcombined hydroxychloroquine with an antibiotic to treat patients with COVID-19, and reported promising preliminary results. Some controversy continues about possible side effects. Chloroquine has accrued a very good safety profile in combatting malaria over many years; however, most treated populations have been young. Could the antimalarial drug cause toxicity in elderly persons (in particular those with cardiac arrhythmias), especially when a high dose is needed to efficiently control viral multiplication? The U.S. and several other countries are launching randomized controlled studies to carefully answer this question.

It may be too late in the disease process if we only aim to target the virus. Solid evidence now indicates that immune response and associated inflammation generated by the coronavirus play a major role in the so-called “cytokine storm,” an immune system overreaction driving lung pathology and acute respiratory distress. The interleukin 6 (IL6) cytokine has been identified as an important driver of this harmful inflammation. Also, the risk of long-term respiratory sequelae, such as lung tissue damage and scarring, following apparent recovery has become a concern, although not yet well documented. Interestingly, some studies suggest that monoclonal antibodies inhibiting the activity of the IL6 receptor (i.e., the immunosuppressant tocilizumab) might very significantly benefit those patients with respiratory distress. These drugs have so far been used to treat polyarthritis and an acute systemic inflammatory syndrome (called cytokine release syndrome) caused by CAR-T cell therapy, illustrating the impact of an unbiased repurposing strategy.

Clearly modifying immune response must be carefully evaluated. We have learned when treating patients with sepsis how difficult it can be to control potential side effects. It’s worth noting that preliminary evidence indicates corticosteroids may help those patients with severe respiratory failure — although these inflammation-lowering drugs were initially thought to be toxic, based on previous experience with influenza.

In addition, more upstream research is being conducted to neutralize the virus through antibodies obtained either by molecular biology or even from blood plasma of recovered patients; it is still too early to evaluate the benefits and risks of this approach. (Yesterday, the FDA announced it would expedite treatment of seriously ill COVID-19 patients with this “convalescent plasma.)

Beyond therapeutics against coronavirus, it would be great to provide preventive therapies (prophylaxis) to those with a high risk of infection (such as health care workers) and/or with a high risk of very severe disease (such as nursing home residents). But more data needs to be obtained for prophylactic therapies; with this view, and with further testing, chloroquine and hydroxychloroquine may offer an interesting opportunity, as well as nitazoxanide, a widely used antiparasitic drug with an excellent safety profile and laboratory (in vitro) evidence of its effectiveness against coronaviruses and SARS-CoV-2.

Overall, we have many therapeutic options to pursue with a real chance of success in saving COVID-19 patients from serious harm or death. And, any molecules proven effective will likely need to be combined – attacking the virus on multiple fronts — for optimal treatment of COVID-19.

March 18, 2020

New Findings on Coronavirus

The pandemic caused by SARS-associated coronavirus 2 (SARS-CoV-2) has become a stark reality, and the University of South Florida remains at the forefront of measures aimed at curbing its rapid spread. Leadership continues to closely monitor the evolving coronavirus (COVID-19) outbreak and to provide excellent ongoing communication on the crisis.

In my role as USF Professor and President of the Global Virus Network (GVN), a network of around 50 research centers worldwide, I will work with Linman Li of USF Medicine International (now being recruited as GVN Vice-President) to update you weekly on new findings about the coronavirus pandemic disrupting our lives. Our comments are not intended to replace documents and information issued by USF and USF Health on COVID-19, including the expertise shared by our USF Health Department of Internal Medicine infectious disease colleagues (Seetha Lakshmi, John Sinnott, Asa Oxner, and Kami Kim). Also, with the situation rapidly changing, we wish to emphasize that there is still much to learn about the epidemiology of this virus and how it causes infection.

USF Health’s Christian Brechot, MD, PhD, is president of the Global Virus Network

Epidemiology: Getting the “denominator” right in mortality rates

The mortality rate of this novel coronavirus infection will clearly be lower than estimates currently reported when we actually identify the overwhelming number of infected individuals. That’s because many with very mild or no clinical symptoms will then be counted and added to the overall number of cases encompassed in the “denominator” used to calculate a coronavirus mortality rate. (The numerator is the number of coronavirus deaths reported.)

Yet, recent information indicates that SARS-CoV-2 is highly contagious, with an R0 number (average number of individuals contaminated from a single case) possibly as high as 5 or 6. Under these circumstances, even though mortality rates may be lower than 0.4-0.5% overall, the dissemination of the virus worldwide (with potentially hundreds of millions of cases) will could have a massive casualty rate. COVID-19 will mostly kill old and fragile individuals (present estimates climb from around 2-3% after age 65 to 10% after age 80) — but a number of younger and apparently healthy persons will also die from the virus.

The pandemic threatens to completely overwhelm our health systems and lead to many uncounted side effects for patients with unrelated diseases who will not be correctly treated. This is why we must curb the pandemic now, and there is only one way — social isolation, that is, separating infected people from healthy people. The good news is that this method works: China has obtained a massive reduction of new infections. And in Codogno, the city where a coronavirus epidemic initiated in Northern Italy, a drastic lockdown has led to a very significant reduction of new infections after three weeks. How long should a lockdown last? This is a difficult questions, but governments should consider at least maintaining aggressive measures for about two months.

Linman Li of USF Medicine International

Pursuing treatment options

Several coronavirus vaccines are in different stages of development. When proven successful and approved, a vaccine will be very useful in combating any reemergence of SARS-CoV-2 — but it is not available to help us now. The scientific community worldwide is stepping up both to develop new therapeutic molecules and to repurpose drugs currently used for other diseases. The Global Virus Network is at the forefront of this ambitious task, synergizing the activities of the GVN centers and providing input to complement the efforts of national and international research agencies.

No antiviral therapy exists specific to either this new coronavirus, SARS-CoV-2, or the original SARS virus, SARS-CoV, which caused a swift global outbreak in 2003. That is why some clinical studies are testing antivirals proven to be effective for other viruses, in particular, retroviruses such as HIV. A complementary approach is to target the immune response, which clearly plays a critical role in the development of an acute respiratory syndrome in certain patients (to be further explained in the next blog).

Earlier this month, an international preclinical study published in Cell offered some good news. Researchers already knew that SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) to enter cells. A complex and multistep process allows SARS-CoV cell entry and infection to happen. It involves binding of the “spike” of the coronavirus (the viral S protein) to the ACE molecule and then cleavage of this S protein by a cellular serine protease known as TMPRSS2. The new study shows the same process holds true for SARS-CoV-2. Most importantly, the researchers demonstrated that a molecule inhibiting TMPRSS2 activity – a protease inhibitor previously used for another clinical indication in Japan — can block the infection of human lung cells. Also, antibodies obtained from patients who recovered from SARS-CoV-2 infection can block entry of the virus, thus providing a neutralizing action. This promising work defines potential treatment targets that may protect against SARS CoV-2 infection.

Dr. Brechot has served as president of the Global Virus Network since 2017, and is past president of the world-renowned Pasteur Institute.

University of South Florida

University of South Florida

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