What do variants and vaccines mean for COVID-19’s ‘new normal’?

Kicking off the academic year with the first of its weekly “The World Today” seminars, Perry World House hosted an in-depth discussion with vaccine safety expert Paul Offit and virologist Susan R. Weiss on the future of COVID-19. During the online event, moderated by Jennifer Pinto-Martin, Offit and Weiss shared their expertise on vaccines and viruses while discussing how coronavirus variants arise, the effectiveness of current vaccines, and how public health measures might evolve.

After an introduction by LaShawn Jefferson, deputy director of Perry World House, Pinto-Martin, a new Perry World House fellow and a member of Penn’s COVID response team, compared the pandemic to the climate crisis: “Things are changing so rapidly, more rapidly than anyone anticipated, and this means that we are forced to make decisions in a climate of imperfect and incomplete information. It makes for a very challenging situation,” she said.

To help shed light on the challenges of COVID-19, Pinto-Martin first asked Weiss, who has been studying coronavirus biology for more than 40 years, to talk about SARS-CoV-2, the virus that causes COVID-19, and how variants of this virus emerge.

Weiss explained that coronaviruses use RNA as their genetic material instead of DNA, and their imprecise replication enzymes make it easy for random mutations to be introduced into the virus’ genetic code. While most mutations are either neutral or detrimental, she said, occasionally a mutation will create a variant that allows it to spread or infect cells more easily.

The COVID-19 vaccines continue to work well against the known variants of concern for SARS-CoV-2, she said, and none of these variants exhibits epitope escape, meaning that the variant has a mutation that protects it against a specific antibody mounted by the host’s immune response. “Because variants arise when viruses replicate, if we would get everybody vaccinated, I think that’s the best insurance against making further variants. Variants are just a byproduct of replication, and making the virus stop replicating is the best medicine to get rid of them,” she said.

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Pinto-Martin then asked Offit about COVID-19 boosters. He said that the greater-than-90% efficacy rates for the two mRNA vaccines set public expectations high for these vaccines. He added that, despite news about “breakthrough” infections, these vaccines are still achieving their goal of preventing severe disease. He also explained that an erosion of protection against mild or asymptomatic infections is expected for vaccines and is not a sign that a vaccine is ineffective.

“The thinking behind this is that because they are seeing an erosion in protection against mild or asymptomatic infection that right around the corner is going to be a loss in protection against serious disease," Offit said about the White House's annoucement about boosters eight months after the first dose of a two-dose vaccine. "That’s unlikely to be true because usually protection against serious disease is much easier; it’s much easier to keep your entire house from burning down than it is from preventing a small fire in the kitchen."

With neither the CDC nor the FDA is yet officially recommending a booster dose for the general population, Offit emphasized that “people who have gotten two doses of an mRNA vaccine should feel they are protected against severe disease and not feel they are under-immunized.”

When asked by Pinto-Martin about the most effective use of currently available COVID vaccines, both Offit and Weiss agreed that vaccinating the rest of the world and reaching unvaccinated parts of the United States were more crucial to ending the pandemic, and preventing newer, more dangerous variants from emerging versus giving out third-dose booster shots.

“The problem in this country right now is that we continue to see tens of thousands of cases and hundreds of deaths, not because we haven’t boosted the vaccinated but because we haven’t vaccinated the unvaccinated,” Offit said. “Until we do that, we are not going to get on top of this pandemic.”

Both Weiss and Offit also said that it’s challenging to separate the impacts of delta’s mutations on its transmissibility with a concurrent change in behavior. “When delta started flourishing, it was a time when people started really hanging out together in groups. I believe delta is more transmissible, but I’m not sure how much,” said Weiss.

Pinto-Martin fielded questions from the audience on a range of topics, including whether COVID-19 will become endemic, universal vaccine development, the need for new antiviral treatments, natural immunity versus vaccination, the challenges of reopening schools for children who are unvaccinated, and the timeline for vaccine approvals for children younger than 12.

Offit and Weiss also shared their thoughts on personal behaviors during the pandemic, emphasizing the importance of mask wearing while indoors and modifying behaviors based on local viral-circulation levels. Pinto-Martin said that, because of testing and high vaccination rates at Penn, the campus will be “one of the safer places to be” this fall.

“For myself, I don’t really feel that nervous,” Weiss said about a future living with COVID-19. “I’m staying mostly around people that are vaccinated, wearing a mask when I have to, and spending time outside. I think we’ll slowly get back to normal. I’m optimistic.”

A video of the virtual talk can be seen on Perry World House’s YouTube channel.

For online resources about COVID-19, the panelists recommend CHOP’s Vaccine Education Center, the Center for Disease Control and Prevention (CDC), Vaccinate Your Family, and Johns Hopkins University’s Coronavirus Resource Center.

Paul Offit is the Maurice R. Hilleman Chair of Vaccinology in the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. He is also the director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at the Children's Hospital of Philadelphia.

Jennifer Pinto-Martin is the Viola MacInnes/Independence Professor of Nursing and executive director of the Center for Public Health Initiatives in the Penn School of Nursing and professor of epidemiology in Penn’s Perelman School of Medicine.

Susan R. Weiss is a professor in the Department of Microbiology in Penn’s Perelman School of Medicine.