In the wake of the discovery of the Omicron variant of COVID-19, the CDC modified its guidance on booster vaccines. The agency now says that all adults should get a booster vaccine dose if at least 6 months have passed since their initial mRNA vaccine series (or 2 months for Johnson & Johnson recipients). For some time, there have been differing opinions over the benefit of universal boosting, especially for healthy younger individuals. Now it is important to consider whether Omicron changes the calculus.
A booster dose has clearly been demonstrated to be beneficial for certain populations. However, the net benefit of rushing to boost the average healthy person is less clear, especially in the context of the potential need for an Omicron-specific vaccine in the near-term and considering the global fight against COVID-19, which depends on first and second doses.
Studies have established, unsurprisingly, that a booster dose increases antibody levels and is, at least temporarily, likely to stave off a breakthrough infection. But with a destined-to-be endemic coronavirus, a breakthrough infection (symptomatic or asymptomatic), especially with our current vaccines, is likely for most people. For those at heightened risk for severe COVID-19, preventing a breakthrough infection from becoming severe is very important. Anyone over 65 or who has underlying conditions should be boosted as soon as possible. But for most people who are not at high-risk for severe COVID-19, any breakthrough infection will be unlikely to cause severe illness, hospitalization, or death. Therefore, for the young, healthy population, the value of boosting with the vaccine currently available to transiently prevent what would likely be non-severe illness is, to me, of marginal value. The likelihood of non-severe COVID-19 in young, healthy people is almost certain to be as true for Omicron as it has been for Delta, and we will learn more in the coming days and weeks.
For the CDC, however, the appearance of Omicron with its mutation profile, which includes changes that have been associated with less protection from the vaccine, was enough to universalize stronger booster recommendations for all adults. However, this action appears to be a preemptive move done without any new publicly released data to undergird it. The likely rationale behind the change may be that higher antibodies, even against an evasive variant like Omicron, may prevent infection. Though this is plausible, there isn't data yet to support this. But, again, a breakthrough infection with Alpha, Beta, Delta, Lambda, Epsilon, Gamma, or Omicron is still most likely a non-severe COVID-19 infection and will likely be less contagious than infection in an unvaccinated person who, as South Africa is reporting, are more likely to test positive for this variant. The non-severe nature of breakthrough infections is a testament to the success of the vaccines at preventing what matters: serious illness, hospitalization, and death.
Even if the Omicron variant does prove to evade some of the protection engendered by our current COVID-19 vaccines, it is extremely unlikely that this variant can erase everything a vaccine does -- especially the most important attribute: protection against serious illness. These vaccines give us a panoply of immune protection, including the extremely critical (but hard to measure) T-cell immunity. Early (albeit limited) data from South Africa does seem to support that the majority of those hospitalized are not vaccinated.
If Omicron is indeed confirmed to be a major problematic variant, a specific variant-targeted booster will need to be developed. Vaccine manufacturers are reportedly already working on this. While there have been no safety indications to getting a booster dose to date, Paul Offit, MD, Marion Gruber, PhD, MS, and Philip Krause, MD, write in The Washington Post:
"...'training' the immune system repeatedly on the original variant -- as the current boosters do -- may prove to be counterproductive. It could, for instance, diminish the effectiveness of a reformulated booster. In other words, for those not in immediate need of a boost, there may be an advantage to waiting until a booster more closely aligned with circulating variants becomes available."
What they are referring to is a fascinating phenomenon called "original antigenic sin" in which the immune system will respond to a pathogen in a way shaped by its first exposure to it regardless of how the pathogen may have changed. This could blunt the response to altered boosters (an Omicron-specific booster, for example) because when the boosters activate the immune system, the original response is recalled and hampers the ability of immunity more specific to the new version of the pathogen from being developed. The late DA Henderson, MD, MPH -- the architect and commander in chief of the only successful attempt to eradicate a human infectious disease from the planet, and the founder of the Johns Hopkins Center for Health Security -- and I wrote about original antigenic sin and how it explained the patterns of severe illness during the 2009 H1N1 influenza pandemic. In the context of Omicron, it's worth considering how original antigenic sin factors into discussions of boosting young, healthy adults with the current COVID-19 vaccines.
Finally, the emergence of Omicron demands renewed attention to the global fight against COVID-19. The new variant emerged in an area of the world with very low vaccination rates (only a quarter of the South African population is fully vaccinated, for example). This is not surprising. COVID-19 will continue to pose a threat as long as there remain pockets of unvaccinated people in the U.S. and around the world. First and second doses determine the trajectory of the pandemic. This is where the focus must remain. If all healthy 18- to 50-year-olds were boosted in the U.S., Omicron would still have emerged. Prioritizing first and second doses for people who remain unvaccinated around the world is key.
Omicron, which merits much study and characterization, illustrates that until the world has baseline immunity to this virus through vaccination, COVID-19 will continue to be a deadly and disruptive force.
Amesh Adalja, MD, is a senior scholar at the Johns Hopkins Center for Health Security and a practicing infectious disease, critical care medicine, and emergency medicine physician.
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