Make of it what you will in an unpredictable pandemic, but one of the nation’s leading vaccine and immunology experts sees COVID-19 fading to a somewhat undefined endemic level and then returning as a seasonal virus next winter.
Since the original SARS-CoV-2 emerged in late 2019, a succession of variants has followed — each more contagious than its predecessor, said Paul Offit, MD, director of the Vaccine Education Center and professor of pediatrics in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.
“But in all cases, the vaccine protects against serious disease, because the immunological mediator of protection against serious disease are memory cells,” Offit said in a recent interview.1 “[These include] memory B cells, and especially memory T cells, memory T helper cells, memory cytotoxic T cells. Those cells recognize more conserved regions of the SARS-CoV-2 spike protein. I think that’s why you see consistent protection against serious illness. Even with two doses of an mRNA-containing vaccine, you are protected probably for years against serious illness.”
A member of the FDA’s vaccine advisory committee, Offit said the duration of protection against serious illness likely would make annual shots or boosters unnecessary.
“The goal for this vaccine — which is the goal for any mucosal viral vaccine, like rotavirus or flu vaccine — is to protect against moderate to severe illness,” he said in an interview with Mira Irons, MD, president of the College of Physicians of Philadelphia. “This vaccine does that. What’s the advantage of that third dose? What the third dose does is it increases neutralizing antibodies against the circulating virus for about three to four months.”
The only groups in whom the third dose has been shown to increase protection are people age 70 years and older, and residents of nursing homes. Those who are immunocompromised, or who are age 50 years and older with comorbidities, also are appropriately indicated for boosters.
“But I do not see why we are giving booster doses to healthy young people, nor does the World Health Organization, which put out a statement2 that said exactly that,” Offit noted. “I’d like to think we are going to get away from this booster dose story, because for the most part, for healthy people, two doses of mRNA-containing vaccines, for example, appears to provide long-term protection against serious disease.”
Endemic Could Mean Thousands of Deaths
As SARS-CoV-2 becomes endemic, it will likely decline and then reach peak circulation in the winter months worldwide. Endemic means it will be more controlled, but COVID-19 still could be a seasonal killer along the lines of influenza.
“Two years before this pandemic, influenza in the United States caused 700,000 hospitalizations and 60,000 deaths,” Offit said. “The year before the pandemic, it caused roughly 400,000 hospitalizations and 20,000 deaths. That’s not considered a pandemic. Basically, that’s considered an endemic winter virus. I think by next winter, we will probably feel that this virus falls into that category.”
Patsy Stinchfield, RN, MS, CPNP, president-elect of the National Foundation for Infectious Diseases (NFID), clarifies this issue further. “‘Endemic’ does not mean ‘end’. I think people are getting mixed up on this,” she explains. “It means that it will join the backdrop of our usual circulating viruses, and then we’ll have to deal with [SARS-CoV-2] in a seasonal kind of way. We’re looking forward to this, but we’re not there yet.”
A high level of population immunity will be needed for years, if not decades, Offit said. “This virus is circulating throughout the world, and it’s going to be for a long time.”
There has been discussion and research into a combination influenza/SARS-CoV-2 vaccine that could cover both viruses, but Offit said there is an inherent problem with this idea.
“The influenza virus mutates to a much greater extent than coronaviruses do,” Offit said, casting doubt on the theoretical combo vaccine. “I think the most practical message is to get vaccinated [for SARS-CoV-2]. We’re not going to boost our way out of this pandemic any more than we’re going to test our way out of this pandemic. We’re only going to be able to vaccinate our way out of this pandemic.”
The COVID-19 testing issue “is a mess,” Offit said bluntly.
“I’m trying to think of a nice way of saying this, but what do you really want to know when you get a test?” he asked. “What you really want to know is, ‘What is the quantity of infectious virus that I’m shedding, and does that quantity correlate with infectiousness?’ We don’t have that test. That is not a commercially available test.”
Antigen tests identify viral protein, but are not without confounding variables, such as where a person is in the course of infection at the time of the test.
“The PCR test — forget the PCR test,” Offit said. “The PCR test detects viral genome. It doesn’t detect whole virus at all, or even viral protein. You usually shed infectious virus for about five to seven days, so you’re contagious for that period of time. But you can be PCR-positive for three months. Using a PCR test to get out of quarantine is ridiculous. Worse, it’s misleading.”
The CDC has been lambasted by some because it has changed guidelines to match the demands of a changing virus and the continuous flow of research it is generating. That this represents some kind of error — that changes should not be made in the face of new science — is pure dogma, of course. But CDC Director Rochelle Walensky, MD, MPH, has been attacked along these lines as a poor communicator. Offit begged to differ, calling Walensky “brilliant” and “empathetic.”
“I would love to see Rochelle Walensky in front of the media every two days — tell us where we are, tell us what the data show,” Offit said. “She’s the perfect person for this, but I feel like she’s sort of in the shadows, to some extent, of the NIH and the administration.”
As a pediatrician, Offit said for “children less than [age] 5, I don’t think we’re going to have a vaccine available — certainly not until the middle of this year, if not later, the way the studies seem to be going. Just do the best you can to put a moat around that child so everybody they come in contact with is vaccinated.”
Those age 5 years and older should be vaccinated, particularly if they are going to school. Unfortunately, only about 30% of those ages 5 to 11 years are vaccinated, increasing somewhat to 50% immunization for those age 12 to 15 years.
“The last time I was on service, we admitted 18 kids to the hospital with COVID,” Offit recalled. “All but one of them were over 5, and none of them were vaccinated. Not one. Nor were their parents, nor were their siblings. That’s just unconscionable. I just can’t stand it. This was hard enough before there was a vaccine.”
Offit has long been the point of the spear in the battle against anti-vaxxers claiming the measles, mumps, rubella (MMR) vaccine caused autism in children. This has been thoroughly refuted, particularly by a 2019 Denmark study that followed 650,000 children for a decade.3
“The study strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination,” the authors concluded.
The anti-vaccine movement has become heavily politicized, using the COVID-19 vaccine to undermine immunizations in general.
“The anti-vaccine movement really took off in this country in the early 1980s, and there was not a lot of politics to it,” Offit said. “On the right, it was libertarian — government off my back, don’t tell me how to raise my family. On the left, [the concern] was manufacturing additives or residuals, these sort of ‘unnatural’ ingredients they didn’t want to put in their bodies. In fact, the [2014-2015] measles outbreak that started in Southern California was in a liberal democratic community, from which it spread to 25 states.”
The COVID-19 pandemic was downplayed and politicized when it hit the United States in 2020. Somewhat surprisingly, given the country likely will hit the 1 million death mark this year, many people could never be convinced the vaccine is safe and effective.
“This is a cultural issue now,” Offit said. “Look at counties that voted heavily for former president Trump as compared to heavily for Biden — you are 60 times more likely to die in a county that heavily voted for Trump. I don’t know how you address that. But I have to believe there is a way to do that.”
‘Viruses Don’t Inevitably Evolve Less Virulence’
In addition to vaccination, some evidence exists that prior infections are protective against severe outcome. Indeed, a recent commentary by two epidemiologists argues that it is the immunity from vaccination and prior COVID-19 infection that is largely responsible for the impression that omicron is a “less severe” variant.
The authors of a new study warned “a portion of the observed reduction in severity stems from omicron’s greater ability to infect people with pre-existing immunity, which protects somewhat against severe disease.”4
The authors cited two modeling studies that estimate omicron is about 75% as likely as the delta variant to cause hospitalization in an unvaccinated person with no history of SARS-CoV-2 infection.5,6
“This meaningful but fairly small difference implies that omicron, alpha, and wild-type SARS-CoV-2 have similar intrinsic severity,” they concluded. “Viruses don’t inevitably evolve toward being less virulent; evolution simply selects those that excel at multiplying.”
The immediate implications are those who were not previously infected with SARS-CoV-2 and who remain unvaccinated are at greatest risk of a severe infection with omicron. It also raises an important caveat that could confound Offit’s endemic scenario: The appearance of new variant, which impossibly, it seems, would have to be more contagious than omicron to replace it.
“I think the one thing that the pandemic has given us is a new appreciation for the words ‘novel’ and ‘evolving,’” Irons said. “We used to just kind of throw those out, and now we really know what they mean.”
REFERENCES
- College of Physicians of Philadelphia. Dr. Paul Offit on where we are with the COVID-19 pandemic. Jan. 28, 2022.
- Reuters. WHO’s top scientist says no evidence healthy kids, adolescents need COVID-19 boosters. Jan. 18, 2022.
- Hviid A, Hansen JV, Frisch M, Melbye M. Measles, mumps, rubella vaccination and autism: A nationwide cohort study. Ann Intern Med 2019;170:513-520.
- Bhattacharyya RP, Hanage HP. Challenges in inferring intrinsic severity of the SARS-CoV-2 omicron variant. N Engl J Med 2022;386:e14.
- Davies M-A, Kassanjee R, Rousseau P, et al. Outcomes of laboratory-confirmed SARS-CoV-2 infection in the omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa. medRxiv 2022; Jan 12. doi: https://doi.org/10.1101/2022.01.12.22269148. [Preprint].
- Ferguson N, Ghani A, Hinsley W, Volz E. Report 50 — Hospitalisation risk for omicron cases in England. Imperial College London. Dec. 22, 2021.
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