Thousands of college students in the U.S. may soon help answer one of the world’s most pressing questions about COVID-19 vaccines: Can these shots, which protect against serious symptoms, also prevent those who might still get infected from silently spreading the disease to others?
Designed and managed by researchers at the CoVPN, or COVID-19 Prevention Network, which is headquartered at Seattle’s Fred Hutchinson Cancer Research Center, the study will offer the Moderna COVID-19 vaccine to 12,000 students willing to swab their noses every day for four months during the course of the clinical trial.
Called the Prevent COVID U study, it began enrollment on 21 U.S. campuses this week. It is supported by the National Institute of Allergy and Infectious Diseases, headed by Dr. Anthony Fauci.
Fred Hutch professor and virologist Dr. Larry Corey, who directs operations at CoVPN, said plans for the study began in December. The Pfizer and Moderna vaccines were proven by then to be extraordinarily effective in stopping symptomatic disease, but it was unknown whether vaccinated people could become infected without showing symptoms and spread the virus unwittingly.
“We needed a different kind of study design — one that uses intensive sampling of the nose, the site of first infection, and can detect the exact time-course of infection,” Corey said.
Limited evidence from the current COVID-19 vaccine efficacy trials — as well as data emerging as vaccines roll out in the community — suggest but do not prove that the current COVID-19 vaccines do reduce infection, including asymptomatic infection. The newly launched college study is designed to find out for sure.
Answers from this new trial will likely signal whether the much-anticipated vaccines will usher in a return to life where people can safely congregate in crowded, indoor settings without fear, or if the era of masks and social distancing is likely to be with us for a long, long time.
Results of the trial should be ready in time for students attending college this fall.
Although only the Moderna vaccine will be used in the college trials, Corey said the results will apply equally well to the Pfizer-BioNTech vaccine, which uses a similar technology (called mRNA) to train the body’s immune system to recognize and attack SARS-CoV-2, the virus that causes COVID-19.
“Whatever one learns from Moderna applies to Pfizer,” he said. “The strand of RNA is identical.”
There will be no placebo injections given in this trial. Half of the students (aged 18-26) will be randomly selected to receive the Moderna vaccine on the day they enroll, and the remaining 6,000 will get their first shot four months later.
Those nasal swabs — more than 1.3 million of them — will be stored by the participants and shipped off weekly to a laboratory for the same kind of PCR testing performed by public health clinics to determine if someone is infected with SARS-CoV-2. All 12,000 participants will be prompted to fill out weekly electronic diary checking for symptoms of illness and reminding them to complete their daily swab tests.
During this time, these same participating students will also receive twice weekly real-time COVID-19 tests from their college health clinics so that, if a person becomes positive for the virus, he or she can quickly be isolated and receive appropriate treatment.
Any positive samples found among the daily swabs will be more deeply analyzed to determine how much virus was in them — a measure called viral load. Any viruses detected can also be genetically sequenced to determine which variant of SARS-CoV-2 had infected the individual.
Daily testing is key to giving researchers a better handle on the stealthy nature of SARS-CoV-2. Studies suggest that a person appears to be most infectious for only a few days, and those days are often before the onset — if ever — of any COVID-19 symptoms. Roughly half of SARS-CoV-2 infections remain asymptomatic.
“In the college study, by testing participants every day we can quantify the amount of virus in the nose of those infected — early and throughout the course of infection — and use that to assess the ability of the vaccine to reduce infectiousness,” said Hutch biostatistician Dr. Holly Janes, who helped design the college study. “What we would like to see is that the vaccine recipients who become infected have lower levels of virus in the nose or a shorter duration of infection than participants who became infected and are not vaccinated.”
It would be particularly concerning should this study find that the vaccine only knocks down telltale COVID-19 symptoms but leaves vaccinated people still able to transmit infection. A large increase in the number of asymptomatic spreaders could reverse the obvious advantages of new vaccines shown to cut symptomatic disease by nearly 95%.
Janes said that while the large, ongoing efficacy trials of new COVID-19 vaccines are measuring viral load among infected individuals, they are doing so only in those developing symptoms, after the onset of those symptoms. Therefore, these studies will not capture how much virus is present in a person with asymptomatic infection, or how much virus is present early in the course of infection when most transmission occurs.
The primary goals of the college study are to assess the ability of the vaccine to reduce the infection rate and infectiousness of SARS-CoV-2. A second, crucial component of the trial will focus on documenting cases of transmission among those who live in close proximity to the participating students who become infected and evaluating how well the vaccine reduces actual transmission of infection.
Because the initial focus of vaccine trials was to find one or more that worked, assessing infectiousness and transmission after vaccination has not been a priority in the large-scale trials to date. It has also not been attempted until now, Janes said, because it is so challenging to do it well.
For example, people are most infectious early after contracting the virus, so it is important for researchers to reach and test their contacts as soon as possible. That way, if there is a transmission to a close contact, it can be picked up right away. For this strategy to work, researchers ideally want the names of contacts on hand before any potential transmission.
Charles Drew University
Indiana University – Bloomington
Stony Brook University
Texas A&M – College Station
Texas A&M – Kingsville
University of Arizona
University of California – San Diego
University of Colorado – Boulder
University of Florida – Gainesville
University of Illinois – Urbana-Champaign
University of Kentucky
University of Maryland – College Park
University of Nebraska
University of North Carolina
University of Virginia
University of Washington
Wake Forest Baptist Health
West Virginia University
To meet that challenge, the 12,000 participants assigned to get a vaccine — immediately or four months into the study — will be asked at enrollment to invite their friends, co-workers or housemates to sign up on a roster of close contacts. These are the people most likely to be exposed if a participant becomes infected. If the researchers already have their names on hand, they can be notified quickly.
The researchers plan to sign up 24,000 of these “prospective” contacts. Each will be asked to monitor their health weekly on an electronic diary. In the event one of the participants in the primary study tests positive, their contacts listed would be notified and provided with kits for two weeks of self-testing.
“If they are already enrolled in the prospective contact cohort, we have a better chance of intercepting the transmission closer to the time of infection,” said Dr. Elizabeth Brown, who shares the lead biostatistician role in the study with Janes.
Brown noted that the life of a student becomes chaotic if that person tests positive, so it is helpful to have that list of prospective contacts on hand. Infected students will likely have to relocate for two weeks to dorms set up to accommodate and isolate positive cases.
“They’re probably not really going to be thinking about their contacts at that point in time. They’re going to be packing their stuff,” Brown said.
Should any of the 12,000 original enrollees become infected, they will also be asked if they can recall close contact with someone they had not previously named in the prospective group. Those potentially exposed individuals might also be offered an opportunity to self-test for two weeks as well, swabbing their noses, filling out the electronic diaries and self-administering blood tests during that time.
The original enrollees will also be encouraged to update their list of prospective close contacts during the course of the trial, all in the name of speeding up the process of reaching out to them in the event of an infection.
“If you change partners, for example, or move into a new house, you might have a whole new set of contacts,” Brown said.
In addition to learning whether vaccinated people can still transmit the virus if they develop infection, the study should help researchers acquire a more detailed understanding of how well viral load works as a predictor of infectiousness. Paired with information about actual transmissions among those living in close contact with positive participants, these data might reveal what level of virus in a person’s nose poses the highest risk of infection to others. The study might also identify levels below a certain threshold that appear to pose little or no transmission risk.
College students as a group are at high risk of contracting COVID-19 but are far less likely than their parents or grandparents to become dangerously sickened by it. That makes them well-suited for a study that might benefit all generations. There have been 535,000 cases recorded among U.S. college students since the start of the pandemic, 120,000 of which occurred in this year alone, according to a New York Times survey.
Students will be eligible to enroll from a group of participating U.S. colleges and universities chosen because they have already instituted twice-a-week testing of their students as way to control the spread of COVID-19 on their campuses. That will assure they have the capacity for frequent testing required for participants in the new study.
Among them are the University of Washington, which operates one of the largest PCR laboratories in the nation. Also participating are two HBCUs, Historically Black Colleges and Universities: Morehouse College, in Atlanta; and Charles R. Drew University of Medicine and Science, in Los Angeles. (see sidebar above for a list of currently participating colleges and universities.)
“I can’t overstate the enormous service these students are doing for public health by participating in this study,” Brown said. "They are really giving a lot of themselves to do this, and we really appreciate their effort and contribution to science.”
Sabin Russell is a staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT, and a freelance writer for the New York Times and Health Affairs. Reach him at email@example.com.
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