Dr. Brechot’s Health Research & Care Blog – April 8, 2020

Vaccine development challenges and the debate over masks

 April 8, 2020

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 7th 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.

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

 

 

 

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

April 1, 2020 — 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 developed and 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

 

 

 

 

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

March 25, 2020 – 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.

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

 

 

 

 

 

New Findings on Coronavirus

March 18, 2020 — 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.

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

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