Tracking SARS-CoV-2 and its Evolving Variants

The panel on the left shows the host cell with an ACE2 receptor, which is the binding target for the SARS-CoV-2 virus spike protein that mediates entry into the cell. An antibody competes for binding with the ACE2 receptor and blocks (or neutralizes) this interaction. The panel on the right shows that even when an individual mutation (highlighted in red) disrupts or reduces the binding affinity of antibodies to one area of the spike protein, the body’s immune response to infection or vaccination typically generates a spectrum of antibodies that target different areas of the virus.

A new variant of SARS-CoV-2, the virus that causes COVID-19, appeared in Great Britain in greater frequency in December and has been reported in New York State. The new variant appears to spread more rapidly than older ones and has a distinct set of genetic changes, or mutations. This prompted renewed vigilance among scientists throughout the world who carefully monitor mutations of the virus within their own countries and share their data on public repositories. The genetic codes of 250,000 virus samples from all over the world have already been shared, according to the World Health Organization. Moreover, another new SARS-CoV-2 variant that appears to spread more quickly, but that is different from the English one, has been found in patients with COVID-19 in South Africa.

The Mount Sinai Health System’s Pathogen Surveillance Program continually studies the evolution of SARS-CoV-2 variants through genetic sequencing, a technique that allows them to examine the genetic composition of the virus and identify changes in its genetic code. The team’s work has yielded a series of firsts. Last spring, they reported that the first wave of SARS-CoV-2 in New York City started with several independent introductions of viruses that could be traced back to Europe. These studies also provided evidence for untracked community transmissions of the virus in February and March of 2020.

Mount Sinai Today recently discussed the latest SARS-CoV-2 variants with two leaders of Mount Sinai’s Pathogen Surveillance Program: Viviana Simon, MD, PhD, Professor of Microbiology, and Medicine (Infectious Diseases); and Harm van Bakel, PhD, Assistant Professor of Genetics and Genomic Sciences.

Has Mount Sinai’s Pathogen Surveillance team found this new UK variant in New York City?

Harm van Bakel, PhD

Dr. van Bakel: Although the UK variant has now been detected in New York State, in Saratoga Springs, we have not yet encountered it in our ongoing surveillance of patients cared for by the Mount Sinai Health System. Considering that New York City is a major hub for international travel we fully expect this to change as we continue to generate more data.

This new variant of SARS-CoV-2 from the United Kingdom has a set of distinct mutations—23 to be precise. Does that make it particularly noteworthy?

Dr. van Bakel: SARS-CoV-2 is a virus that tends to mutate slowly and the multiple mutations in this UK variant do make it different. Usually about one to two mutations occur each month. Mutations occur randomly and most of them do not change anything for the virus. But sometimes an occasional mutation makes it more transmissible or potentially less susceptible to existing immunity.

Viviana Simon, MD, PhD

Dr. Simon: There is some emerging evidence that the UK variant, termed B.1.1.7, is more transmissible, although that data is still being worked on. Importantly, there is no evidence that this variant is more deadly. One of the mutations in the UK variant is located within the receptor binding domain (RBD) of the virus’s spike protein, so that has created some concern. The RBD is an area of the virus that attracts a strong immune response from the human body. It is the area where the spike meets the cell receptor and where many neutralizing antibodies bind to prevent the virus from entering the cell.

Dr. van Bakel: A few months ago another variant arose in Danish mink farms that carried a different mutation in the RBD. We have also occasionally seen other RBD mutations as part of our surveillance efforts in New York City during the past few months. When this happens, the worry is that these variants can reduce the effectiveness of existing immunity, but we have not seen any evidence of that yet. There is also always a concern that the viruses become more infectious when they jump from humans to animals such as mink and back into humans. But thus far, we have not seen anything that points to this.

What can we say about this variant so far?

Dr. Simon: It is really important to note that there is no data suggesting that the UK variant is more dangerous or lethal. We are actively doing surveillance on this British variant. We are also looking at other variants that we know are in our city and in Mount Sinai’s patient populations. Starting in September, we began to notice a slow increase in diversity of SARS-CoV-2 detected in the patients seeking care at the Mount Sinai Health System. This is not surprising because SARS-CoV-2 is an RNA virus, and like other RNA viruses, such as influenza and HIV, the more people are infected, the more viral diversity is observed. SARS-CoV-2 does mutate more slowly than influenza viruses or HIV and the majority of these mutations are meaningless insofar as the properties of the virus remain unchanged.

Dr. van Bakel: We are waiting for functional data on the UK variant to tell us if there are differences with regard to how antibodies neutralize it. These data will come from already ongoing controlled experiments using sera from COVID-19 survivors as well as from vaccine recipients. Some genetic changes can render the virus more transmissible. For example, most of the SARS-CoV-2 variants circulating globally over the past 10 months carry a D614G mutation in the spike protein. Studies in animal models have shown that this mutation allows improved transmission compared to the original viral variant first reported in China. Similar studies are needed to determine if this is also the case for the distinct mutations seen in the UK variant.

Is there any evidence that the newly authorized COVID-19 vaccines will not work against this variant?

Dr. Simon:  We believe all of the new vaccines will be effective against this B.1.1.7 variant, as well as other variants, because the vaccines entice the immune system to make antibodies against different regions of the spike protein, and not only the sections of the RBD that are mutated. The immune responses developed upon vaccination will offer protection, even if we find out the RBD of the viral variants has been slightly changed.

Dr. van Bakel: Wearing face masks, maintaining social distancing, and observing all of the measures that have been put in place to protect oneself, as well as others, are still the most effective ways in controlling the spread of the virus until vaccines are more broadly available. Adhering to these guidelines will be effective regardless of the variant that is circulating.

Dr. Simon: Hope is on the horizon. We have highly protective vaccines, which will be delivered to as many people as possible in the coming weeks and months. Since the case numbers in our area remain worrisome, we really need to be careful and follow the guidelines that work for all SARS-CoV-2 variants.

Why Testing New Medicines in a Diverse Population Is Important

Companies are working to develop new vaccines for COVID-19, and one of the many challenges is ensuring that clinical trials required to test the new medicines reflect the population at large in order to determine how effective the vaccines will be when offered to tens of millions of people throughout the United States.

In this Q&A, Lynne D. Richardson, MD, Professor and Vice Chair of Emergency Medicine, Professor of Population Health Science and Policy, and Co-Director of Mount Sinai’s Institute for Health Equity Research, talks about the latest COVID-19 vaccines, why it is important for clinical trials to include a diverse population, and how well the pharmaceutical industry has done that.

Based on data you have seen about the most advanced COVID-19 vaccines in development, do you think the pharmaceutical companies have done a good job including a diverse group of people in their clinical trials?

They are all committed to trying to include a diverse population into their trials. I think there have been substantial efforts to improve the diversity of the participants in the vaccine trials. From the data I’ve seen, I think they did an okay job, though ideally, the makeup of the folks in the trials would be the same as the distribution of the disease.

Why is it important to have a diverse group of people in the clinical trials for COVID-19 vaccines?

Trials are a way of getting information about how something works. So if you want to know that it works for people of all ages, people of all races, people of all ethnicities, people who have lots of other medical conditions, these people must be in the trial. This is always true, not just for vaccines. In addition, participation in the trials must be representative of the population that is suffering from whatever condition is being targeted by the vaccine, or the treatment. There are certain communities, specifically Black and Hispanic communities, who we know are being harder hit by COVID-19, both in the chance they contract COVID-19, and the severity of the disease if they do get it. That’s why it’s important to have a vaccine that is safe and effective for those communities.

Lynne D. Richardson, MD

In the past, how well have clinical trials included a diverse population, including people of color and those of different socio economic status?

If you go back 40 or 50 years, clinical trials consisted almost exclusively of white men between the ages of 25 and 65. They were considered the ideal subjects. The problem is, it is very hard to extrapolate the results and findings of the trial to types of people who are not participating in the trial. It was about 30 years ago that a big push to improve the gender diversity in clinical trials came with the establishment of an Office of Women’s Health at the National Institutes of Health, and that’s when the federal agencies that sponsored research started paying attention to who actually was participating in trials. It was about a decade later that significant attention to the racial and ethnic diversity in trial participation emerged. So it’s not a new issue. The degree of under-representation even a decade ago was staggering. About five percent of clinical trial participants were Black at a time when Black people accounted for 12 percent of the population. About one percent were Hispanic at a time when Hispanics were 16 percent of the population.

Why has ethnic and racial representation been so poor?

For patients, there is a legacy of mistrust of research, certainly among the African American population, but also mistrust of the health care system in general and of research, specifically among many disadvantaged populations. They are skeptical about the motives and intent of researchers. Also, there are access issues. Most clinical trial participants are recruited through their physicians, and often companies did not include physicians and practices that serve diverse patient populations.

What can be done about that?

Project Impact of the National Medical Association, a national association of Black physicians, has been working to diversify participation in clinical trials for more than a decade by speaking with Black physicians, who often have a group of patients that is much more diverse. They have published results that show that when Black people are approached in the same way, when they are encouraged to participate by a physician with whom they have a relationship, and whom they trust, they participate at the same rates as other groups. But you have to reach out to the physician and the physician practices, where they have those sorts of relationships.

How has the situation changed during the pandemic?

In the era of the COVID-19 pandemic, with Black people and Hispanics being disproportionately impacted by the virus, it’s essential to engage them in vaccine trials. Yet the level of public distrust in the research process and government has never been higher. So we have a lot of work to do if we’re going to get this pandemic under control.  Building trust means developing relationships and that takes time. This is an ongoing challenge in some of the trials and is why Mount Sinai has been approached by many of the pharmaceutical companies because we do have access to this diverse population.

What is Mount Sinai doing?

At the Mount Sinai Institute for Health Equity Research, we have been approached by various entities, asking us to help recruit more diverse populations into their studies. We start by talking about the things you have to do. First, you have to talk with some of our community partners and you have to accept their input, such as the language you use in the materials you distribute to participants. You need to look at how burdensome the trial will be. If we are going to combat mistrust, we must behave in a trustworthy manner.  The Institute is ready to work with researchers who are serious about building the relationships needed to recruit diverse populations into clinical trials.

 

mRNA Vaccine Technology Makes Its Extraordinary Debut

mRNA vaccines must be stored at extremely cold temperatures.

The mRNA technology used to create the first two COVID-19 vaccines from Pfizer Inc., and Moderna, Inc. will undoubtedly change the course of vaccine development for years to come.

Both companies have “shown that the vaccines are extraordinary,” says Peter Palese, PhD, the Horace W. Goldsmith Professor and Chair of the Department of Microbiology, at the Icahn School of Medicine at Mount Sinai. The Pfizer vaccine began being administered to high-risk U.S. health care workers on Monday, December 14. This marks the first time mRNA technology has ever received authorization for use in a vaccine. Moderna’s vaccine received Emergency Use Authorization from the U.S. Food and Drug Administration (FDA) on December 18. 

“Every single one of the clinical trial participants who received the Pfizer vaccine is thought to have made antibodies against SARS-CoV-2,” which causes COVID-19, says Dr. Palese, who has dedicated his career to the study of vaccinology. Even the 5 percent of participants who did not make enough antibodies to be fully protected made enough to be partially protected against severe disease, he adds. “That is success and that is why everyone is so excited. I hope everyone who is eligible gets vaccinated.”

Like most scientific advances, mRNA technology has evolved over decades. When the COVID-19 pandemic hit in early 2020, mRNA was ready for prime time. The technology was first used successfully in mice in 1990. But it was an unstable molecule that could not be easily transferred into the human body. Over time, improvements in nanoparticle technology enabled mRNA to overcome that hurdle.

This chart shows how messenger RNA vaccines work.

In 2017, mRNA’s safety and efficacy in humans was reported in The Lancet, in a clinical trial of a rabies vaccine. The same year, early human trials began for an mRNA-based Zika virus vaccine. The technology is also being tested for use in cancer vaccines that are now in clinical trials around the world, some in combination with chemotherapy, radiotherapy, and immune checkpoint inhibitors.

Today, synthetic mRNA can be quickly manufactured in a laboratory and engineered to resemble fully mature mRNA molecules that occur naturally in the cytoplasm of the eukaryotic cells of animals. The platform works like a software program that carries the genetic code of the spike protein, an important and easily recognizable portion of SARS-CoV-2. When the code—delivered in a nanoparticle—is injected, the human body begins to make antibodies that recognize and protect against the virus.

The mRNA technology is considered particularly safe since its footprint is so minimal. It does not require the development of inactivated pathogens or small units of inactivated pathogens to trigger an immune response, which is the case with traditional vaccines. In addition, mRNA does not enter the cell nucleus where a human’s genetic material, or DNA, is kept, and leaves the body as soon as it has finished delivering its code. Its main drawback, however, is its high cost due to the intricate lipid preparation of the nanoparticles and the extremely low temperature required to store the vaccines.

Peter Palese, PhD

“If you have mayonnaise and you let it stand, it separates and you get this oily phase,” Dr. Palese says. “It’s the same thing with the mRNA vaccines: they get oily and separate.” The Pfizer and Moderna vaccines require slightly different storage temperatures because they use different lipid particles.

“No shortcuts were taken in the actual scientific development of these vaccines, and we have enough data to know how well they work,” says Dr. Palese. The quick pace of development—which essentially compressed the 10 years it typically takes to develop a vaccine into 10 months, combined with massive amounts of funding—enabled the mRNA vaccines to reach the finish line in record time. Dr. Palese says the closest comparison to such large-scale production took place during World War II during the Manhattan Project, when the United States, the United Kingdom, and Canada joined forces to create nuclear weapons.

In 2020, billions of dollars were provided by the U.S. government, European governments, major corporations, and private donors to fund COVID-19 vaccine development, which, he adds, employed tens of thousands of “really smart people” who were focused on creating safe and successful vaccines.

Dr. Palese expects successful vaccines that use conventional methods will not be far behind those based on an mRNA platform. Within the Icahn School of Medicine at Mount Sinai’s Department of Microbiology, he and his colleagues Adolfo García-Sastre, PhD, and Florian Krammer, PhD, are working on a COVID-19 vaccine that uses an engineered Newcastle disease virus vector. They expect to begin a phase 1 safety trial in January. Dr. García-Sastre is Director of the Global Health and Emerging Pathogens Institute, and Dr. Krammer is Mount Sinai Professor in Vaccinology.

While immediate and widespread COVID-19 vaccinations will help get humanity through the current crisis, scientists fear that SARS-CoV-2 will forever co-exist with humans the same way other infectious pathogens do.

If proven effective, Dr. Palese says Mount Sinai’s low-cost vaccine might be advantageous for use in low and middle-income countries and in young children and infants, who were not part of the mRNA vaccine clinical trials. “Vaccines are good for us,” he says. “They have helped save millions of lives.”

Mount Sinai Researchers Use Apple Watch to Predict COVID-19

Subtle changes in an individual’s heartbeat, which can be measured on an Apple Watch, are able to signal the onset of COVID-19 up to seven days before individuals are diagnosed with the infection. That preliminary observation was made by researchers at the Icahn School of Medicine at Mount Sinai in a new preprint from the Warrior Watch Study, which was recently uploaded to the medRxiv server.

The investigators followed 297 health care workers at the Mount Sinai Health System between April 29 and September 29. The participants downloaded a customized app onto their iPhones and wore Apple Watches. Changes in their heart rate variability (HRV)—a measure of nervous system function detected by the Apple Watch—were used to identify and predict whether the workers were infected with COVID-19.

“The watch showed significant changes in HRV metrics up to seven days before individuals had a positive nasal swab confirming COVID-19 infection and demonstrated significant changes at the time of symptom development,” says the study’s corresponding author Robert P. Hirten, MD, Assistant Professor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai. Daily symptoms that were collected included fever or chills, tiredness or weakness, body aches, dry cough, sneezing, runny nose, diarrhea, sore throat, headache, shortness of breath, loss of smell or taste, itchy eyes, or none.

Interestingly, the researchers also found that seven to fourteen days after diagnosis with COVID-19, the HRV pattern began to normalize and was no longer statistically different from the patterns of those who were not infected.

Robert P. Hirten, MD

“Developing a way to identify people who might be sick even before they know they are infected would really be a breakthrough in the management of COVID-19,” Dr. Hirten says. “One of the challenging things about COVID-19 is that many people are asymptomatic, meaning they have no symptoms but are still contagious. This makes it difficult to contain this infection by using the traditional method of identifying someone who is sick and quarantining them.”

As a gastroenterologist, Dr. Hirten has been an early proponent of using the Apple Watch and other wearable devices to better understand and manage chronic conditions such as Crohn’s disease and ulcerative colitis. He found that measuring HRV in patients with inflammatory bowel disease helps identify and predict periodic flare-ups. “When the COVID-19 pandemic hit,” he says, “we figured, ‘Let’s try to use the advances we’ve made in studying wearable devices to address the crisis.’”

The Warrior Watch Study, which is ongoing and includes a wide range of Mount Sinai employees—from doctors and nurses to security guards—was designed with two goals in mind, says Dr. Hirten. The first goal was to see whether infection prediction was possible by assessing the data that was collected through the end of September. The other goal was to gauge the effects of the pandemic on the mental health of Mount Sinai’s health care workers. This will be addressed in a separate paper.

“This technology allows us not only to track and predict health outcomes, but also to intervene in a timely and remote manner, which is essential during a pandemic that requires people to stay apart,” says the study’s co-author Zahi Fayad, PhD, Director of the BioMedical Engineering and Imaging Institute and the Lucy G. Moses Professor of Medical Imaging and Bioengineering at the Icahn School of Medicine at Mount Sinai.

Digital health is a relatively new field that holds enormous promise. It provides doctors with patient data that would not otherwise be readily available and requires little input from patients themselves. Mount Sinai’s study asks participants to wear the watch for at least eight hours a day and respond to daily questions that inquire about how they are feeling and whether they have been tested for COVID-19.

Apple Inc. and other wearable device manufacturers are very interested in how their products contribute to health care outcomes, as well. In September, Apple’s Chief Executive Officer, Tim Cook, mentioned Mount Sinai’s Warrior Watch Study during the company’s virtual product launch event.

“This study really highlights where digital health is moving,” Dr. Hirten says. “It shows that we can use these technologies to better address evolving health needs, which will hopefully help us better manage disease in the future. While we aren’t there yet, our goal is to operationalize these platforms to improve the health of our patients. The Warrior Watch Study is a significant step in that direction.”

Esteemed Vaccinologist Weighs in on New Vaccines and the ‘Beginning of the End of the Pandemic’

Florian Krammer, PhD, right, filled out the paperwork needed to participate in Pfizer’s COVID-19 clinical trial and discussed the trial with Judith A. Aberg, MD, left, the Dr. George Baehr Professor of Clinical Medicine, and Chief of the Division of Infectious Diseases for the Mount Sinai Health System.

“Dear world, we have a vaccine!”

Florian Krammer, PhD, Professor of Vaccinology at the Icahn School of Medicine at Mount Sinai recently tweeted this in response to news of the interim results to Pfizer Inc.’s COVID-19 vaccine clinical trial, which showed high efficacy in the final, phase 3 round of human testing. “This is the best news since January 10,” Dr. Krammer added. On that date, China released the genome of SARS-CoV-2, the virus that causes COVID-19. Dr. Krammer’s laboratory at Mount Sinai immediately moved from developing a universal flu vaccine to creating the first test to detect the presence of antibodies to SARS-CoV-2 and the first to measure the amount of antibodies.

By November 17, Pfizer had updated its phase 3 results to report that its vaccine was 95 percent effective against COVID-19, across age, gender, race, and ethnicity demographics. Only one day earlier, Moderna Inc. confirmed that its COVID-19 vaccine candidate had a very high efficacy rate in its first interim analysis of its phase 3 study, prompting Dr. Krammer to tweet, “Dear world, we have a second vaccine.”

Both the Pfizer and Moderna vaccines are based on new RNA technology. Rather than containing pieces of an actual virus, as traditional vaccines do, these vaccines contain molecular instructions in the form of messenger RNA (mRNA) that tell human cells to make the virus’s spike protein, the immune system’s key target for the virus. If all goes well, the patient’s immune system will react by making antibodies to the spike protein—and these antibodies will also latch on to the spike protein of the real virus and disable the virus.

“This is the beginning of the end of the pandemic,” says Dr. Krammer. But important questions concerning COVID-19 vaccines still remain. This fall, he volunteered to take part in the Pfizer COVID-19 vaccine clinical trial under way at Mount Sinai and other locations in the United States and abroad. Like the other 43,538 trial participants, Dr. Krammer does not know whether he received a placebo or the real vaccine, which is how the placebo-controlled, randomized, observer-blinded vaccine trial is designed.

Mount Sinai Today recently asked Dr. Krammer to explain Pfizer’s phase 3 vaccine results.

Why are you enthusiastic about the Pfizer vaccine?

The results from the phase 3 trial have to be seen in the context of preclinical data, phase 1 and phase 2 trials, where Pfizer showed the vaccine worked in nonhuman primates. Also, in early clinical trials the vaccine induced good neutralizing antibody responses. Now, in addition to that, we get efficacy results—reduction of the incidence of disease in the vaccinated group—that are in the 95 percent range. Ninety-five percent is pretty good. Even a vaccine that affords 50 percent protection against severe disease would be positive news.

What questions do you have concerning the Pfizer vaccine?

Right now, Pfizer is reporting that the vaccine has 95 percent efficacy against symptomatic disease. That will likely protect at-risk individuals from severe disease outcomes. But we still don’t know if the vaccine can protect from asymptomatic infection. If it doesn’t, would it stop vaccinated individuals from spreading the virus to others? It will be difficult to determine if the Pfizer vaccine can achieve this, because it would involve routinely testing trial participants for the presence of virus, and you can’t do that with almost 45,000 people. Also, how long-lasting will the protection be? In other words, will the vaccine’s efficacy decrease over time, requiring people to get revaccinated?

Do Pfizer’s interim results bode well for other COVID-19 vaccines in the pipeline?

This is looking good for many of the other vaccine candidates. The fact that Pfizer’s vaccine is based on inducing neutralizing antibodies that protect from symptomatic infection might mean that many other vaccines are likely to work as well. Moderna’s vaccine is almost identical in terms of the immune response. Others are similar too.

What are Pfizer’s next steps?

Now that Pfizer has filed an Emergency Use Authorization application with the U.S. Food and Drug Administration (FDA) and the FDA has authorized the emergency use of the vaccine, it is likely that the vaccine will only be available for high-risk groups and front-line workers at first. Over time more people will get vaccinated but this will take months. Now, while we wait for the vaccine, we must keep the virus circulation down. Mask up, physically distance, and stick to guidelines and regulations.

Do any of these concerns dampen your enthusiasm for the vaccine?

No. From my point of view there is a light at the end of the tunnel. Right now, we need a vaccine that works, even if it would only protect for a few months or doesn’t completely stop transmission. That’s what we need to get halfway back to normal. We’ve been in this for 10 months. We can do it for a few more. We have to be patient.

New England Journal of Medicine Study of Marine Recruits Provides Lessons in Controlling the Spread of COVID-19

To effectively control the spread of SARS-CoV-2, the virus that causes COVID-19, public health measures such as wearing face masks, social distancing, and handwashing must be combined with repeated and widespread testing. That is the conclusion of a new study in The New England Journal of Medicine by researchers from the Icahn School of Medicine at Mount Sinai and the Naval Medical Research Center, who looked at disease transmission among 1848 Marine recruits between May and July 2020.

The researchers studied the Marine recruits, the majority of whom were male and between the ages of 18 and 20, while they were in a two-week supervised quarantine. The study results, published on November 11, showed that few infected recruits had symptoms before diagnosis of SARS-CoV-2 infection, that transmission occurred despite implementing many best-practice public health measures, and that diagnoses were made only by scheduled tests, not by tests performed in response to the daily temperature checks and symptom screening of the recruits.

“If you rely only on testing you are going to miss cases and the virus will escape, and if you just use public health measures it’s not going to be sufficient,” says the study’s senior author, Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology at the Icahn School of Medicine at Mount Sinai. “If you do both of them together you should be able to control this highly infectious virus. We hope this information helps in developing more effective measures to keep military installations and schools safe.”

The study data revealed asymptomatic spread of the virus even under strict military orders for quarantine and public health measures that most likely experienced better compliance than would be possible in other youth settings like college campuses. The researchers noted that the virus was largely transmitted within a given platoon group which trained and ate together while maintaining social distancing, handwashing, and other methods of infection control.

The study enrolled participants from nine different Marine recruit classes, each containing 350 to 450 recruits, between May 15 and the end of July. The participants were offered enrollment in a prospective, longitudinal study after self-quarantining at home for two weeks prior to arrival at basic training. Once they arrived, they were required to follow strict group quarantine measures with two-person rooms for two weeks—the duration of the study period—before the start of the actual training. The supervised group quarantine took place at a college used only for this purpose. Each recruit class was housed in different buildings and had different dining times and training schedules, so the classes did not interact.

Each weekly class was further divided into platoons of 50-60. During the study period, all recruits wore cloth masks, practiced social distancing of at least six feet, and regularly washed their hands. Most of their instruction, including exercising and learning military customs and traditions, was done outdoors. After each class finished quarantine, a deep cleaning, using bleach on surfaces, occurred in all rooms and common areas of the dormitories before the arrival of the next class.

To determine asymptomatic and symptomatic SARS-CoV-2 prevalence and transmission during supervised quarantine, participants were tested within 2 days of arrival, at 7 days, and at 14 days using a nasal swab (PCR) test authorized for emergency use by the U.S. Food and Drug Administration. Analysis of viral genomes from infected recruits identified multiple clusters that were temporally, spatially, and epidemiologically linked, revealing multiple local transmission events during quarantine.

“The identification of six independent transmission clusters defined by distinct mutations indicates that there were multiple independent SARS-CoV-2 introductions and outbreaks during the supervised quarantine,” says the study’s co-senior author, Harm van Bakel, PhD, Assistant Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. “The data from this large study indicates that in order to curtail coronavirus transmission in group settings and prevent spill-over to the wider community, we need to establish widespread initial and repeated surveillance testing of all individuals regardless of symptoms.”

Insight into COVID-19 characteristics and SARS-CoV-2 transmission in military personnel has relevance to developing safer approaches for related settings composed primarily of young adults such as schools, sports, and camps.

This work was supported by the Defense Health Agency through the Naval Medical Research Center and the Defense Advanced Research Projects Agency.