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December 8, 2020

The 5 biggest unanswered questions about a coronavirus vaccine

Daily Briefing

    The United States may soon have an authorized vaccine against the new coronavirus, but there are still a number of unknowns about the virus and potential vaccines that must be answered before Americans can expect a return to pre-pandemic normalcy, experts say.

    A vaccine approval is coming. Get ready to ask these 8 questions.

    STAT News spoke with dozens of bioethicists, epidemiologists, public health experts, state officials, and others to learn about the opportunities a potential coronavirus vaccine offers—and the related challenges going forward. Here are five big vaccine-related questions that experts say still need to be answered.

    5 coronavirus vaccine questions that still need to be answered

    1. How do we quickly—and safely—distribute the vaccine so it gets to the right people?

    Operation Warp Speed, led by Army Gen.l Gustave Perna, has set a goal to begin vaccinating Americans against the novel coronavirus within 24 to 48 hours of FDA issuing an emergency use authorization for a vaccine candidate. But some experts have concerns about that fast pace.

    "There are things that the armed forces do amazingly well, and logistics is one of them. And logistics is a big challenge for this vaccination program," Tom Frieden, a former CDC director, said. "But logistics is just one of many challenges for the program. And the impression I have is of a program being run as a logistics challenge, rather than a vaccination program with a logistic challenge within it."

    Claire Hannan, executive director of the Association of Immunization Managers, similarly said the health care space creates unique challenges that people outside of the industry may struggle to understand. "Organizing a clinic and clearing space and having throughput and scheduling appointments and really educating your employees on the need to get vaccinated and the value—difficult to do that when you're putting out fires and trying to find bed space and dealing with a surge in patients," Hannan said.

    Funding is also a concern, STAT News reports. So far, Congress has allotted $340 million to vaccination efforts, but the Association of Immunization Managers and the Association of State and Territorial Health Officers say they need $8.4 billion to recruit and train extra workers, launch education and awareness campaigns, and update software programs that will be needed to track who receives a vaccine.

    Another part of the distribution puzzle is determining who should get the vaccine first. Mike Ryan, head of the World Health Organization's health emergencies program, said vaccination programs should be targeted to vaccinate people who are most likely to transmit the novel coronavirus.

    But Marc Lipsitch, an infectious diseases epidemiologist at the Harvard T.H. Chan School of Public Health, said, "I'm of the opinion that if we vaccinate the very old and the people with significant comorbidities … that would be the quickest way to get back towards a more normal life."

    Operation Warp Speed's current plan prioritizes health care workers, and the Advisory Committee on Immunization Practices, which advises CDC, is expected to recommend vaccinating essential workers, including teachers, before vulnerable populations such as adults older than 65 and people with chronic health conditions, STAT News reports.

    2. What kind of side effects will a vaccine have?

    Another big question is whether authorized coronavirus vaccines will have any long-term or rare side effects, STAT News reports.

    Pharmaceutical companies are currently testing their vaccine candidates in clinical trials involving tens of thousands of patients with reports of only mild side effects. However, experts say the vaccine candidates will need to be administered to millions of people to better understand the potential range of side effects associated with the inoculations.

    It's also not yet known if any of the vaccine candidates are linked to long-term side effects that don't immediately present themselves, STAT News reports. "Most vaccine side effects do occur in the short term," Kathleen Neuzil, director of the Center for Vaccine Development and Global Health, said. "But we don't know a lot about [Covid-19], and we don't know a lot about the long-term consequences of [Covid-19]."

    According to Axios, U.S. clinical trials are tracking participants for at least two years to determine whether the vaccines against the novel coronavirus cause any long-term side effects.

    3. Does the vaccine stop transmission of the virus? And how long does immunity last?

    Clinical trial data show that the vaccine candidate developed by Pfizer and BioNTech, as well as the candidate developed by Moderna, are about 95% effective in preventing Covid-19, the disease caused by the new coronavirus. But the trials haven't been able to determine whether the vaccine candidates prevent coronavirus infection entirely, STAT News reports.

    This is a critical question to answer, according to Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health. "We absolutely need to know if these vaccines are going to stop transmission, but no data that we're going to get is going to give us that at this point," he said. "And that leaves me very concerned because so much of our plans for vaccines center around herd immunity."

    As Anna Durbin, a vaccine researcher at the Johns Hopkins Bloomberg School of Public Health, explained, "If [someone who's vaccinated] still [has viral] shedding, of course that brings up the question of how soon can we all go back to normal-normal. And that's going to be a while."

    The only available research on virus transmission rates among vaccinated subjects is in animals, which has shown concerning results, STAT News reports.

    Vincent Munster, a virologist at the National Institute of Allergy and Infectious Diseases' Rocky Mountain Laboratories, tested the coronavirus vaccine candidate developed by AstraZeneca in primates and deliberately exposed them to the new coronavirus. Those with the vaccine didn't develop disease in their lungs, but they did shed the virus, Munster and his team found.

    That said, it's important to note that the research conducted by Munster's team isn't identical to how the coronavirus spreads in the real world, STAT News reports. But Munster said he believes if vaccinated people do get infected with the virus, they'll likely shed less of the virus than unvaccinated people.

    It's also unclear how long immunity to the novel coronavirus lasts, either after receiving a vaccine or after recovering from an infection with the virus, STAT News reports. Research on other coronaviruses has shown immunity doesn't last long, with some people being reinfected within a year, but it's unknown if that's the case with the new coronavirus. Experts say answering both of these questions is essential if the goal is to achieve herd immunity against the novel coronavirus, which modelling studies suggest would require 60% to 70% of U.S. residents to be vaccinated.

    4. How do we overcome public distrust to achieve herd immunity?

    To achieve herd immunity, the public needs to be willing to get a vaccine against the new coronavirus—but polling data suggests many adults, including some health care workers, are hesitant or unwilling to do so, STAT News reports.

    According STAT News, that hesitancy may stem from early missteps in America's coronavirus epidemic, as well as President Trump's public calls for FDA to authorize a vaccine ahead of the Nov. 3 general election.

    Alison Buttenheim, an associate professor of nursing and health policy at the University of Pennsylvania, said the situation has created "justified distrust" among the public.

    "People who don't think twice about vaccinating their kids totally on time, who get their flu shot every year, are in the sort of, 'Hmmm. Might wait six months on this one,'" Buttenheim said.

    5. Is the vaccine safe for pregnant women and children?

    Health care workers are likely to be among the first to receive a coronavirus vaccine. However, according to CDC, about 75% of those workers are women and around 330,000 are either pregnant or breastfeeding, and it's not yet known how safe a coronavirus vaccine is for pregnant women, STAT News reports.

    As it stands, the American College of Obstetricians and Gynecologists (ACOG) says the best option is for pregnant women to be given the choice of getting a coronavirus vaccine.

    "We feel that women who are pregnant and are lactating should not be excluded from what are high priority populations for a Covid-19 vaccine allocation strategy," Linda O'Neal Eckert, liaison for ACOG, said.

    There's a similar research gap for children—and some experts say the current vaccine candidates may not be safe for children, STAT News reports.

    Florian Krammer, a professor of vaccinology at the Icahn School of Medicine at Mount Sinai Hospital, said, "If [the vaccines are] very reactogenic in adults, they (will be) super reactive in children." He added, "I think at some point, we'll think about vaccinating children. And I think that might not be possible with those vaccines."

    Yvonne Maldonado, chair of the American Academy of Pediatrics' infectious diseases committee, in statement said, "We must include children in the trials as soon as it is safe to do so." She added, "This research takes time. If this does not begin soon, it will be less likely a vaccine will be available for children before the next school year."

    Some drugmakers have said they'll test their vaccine candidates in pregnant women after their current Phase 3 trials are finished, and some drugmakers have begun enrolling or are planning to soon enroll children as young as 12 in their clinical trials. However, so far, no research has been conducted on whether coronavirus vaccine candidates are safe and effective in pregnant women or children younger than 12, STAT News reports (Snyder/O'Reilly, Axios, 12/3; Branswell, STAT News, 12/2).

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