News has broken over the last week that both Pfizer and Moderna have asked the federal Food and Drug Administration for authorization of a fourth (or second booster) dose of their respective mRNA vaccines against Covid-19. This news comes on the heels of reports of rising cases throughout Europe and Asia over the past few weeks, many of which seem to be driven by a subvariant BA.2 of the Omicron variant that was responsible for the most recent surge here in the United States, among other places.
Pfizer has requested authorization for this fourth dose specifically for people who are 65 and older, while Moderna has requested approval for all adults. Pfizer’s press release on March 15 said that the request for emergency use authorization of a fourth dose for adults 65 years of age and older was made in response to data collected in both the United States and Israel recently during a time period when the Omicron variant was dominant. The data from the Israeli Ministry of Health, for example, showed that rates of confirmed infections were two times lower and rates of severe illness four times lower among people who received a fourth dose of the vaccine at least four months after their third doses.
Moderna, on the other hand, said that its request for authorization included all adults in order to give the Centers for Disease Control and Prevention and health care providers the flexibility to determine appropriate use for a fourth dose based on age or co-morbidities.
The data these requests were made in response to were also illustrated in recent correspondence published in the New England Journal of Medicine and reported by researchers at Sheba Medical Center in Israel on March 16. They summarized an open-label, nonrandomized clinical study examining the safety of a fourth dose of the Moderna or Pfizer vaccines when administered four months after a third dose and its ability to elicit an immune response.
In their study, antibody levels rose by a factor of 9 to 10 in the group of participants who received the fourth dose, while the control group participants who did not receive a fourth dose saw their antibody levels continue to wane over time. The researchers did not report any significant adverse events, although mild systemic and local symptoms were seen, similar to what has been described after the first three vaccine doses.
Notably, however, this fourth dose did not dramatically decrease risk of infection itself, as 25 percent of the control group (those who did not get the vaccine) were found to be infected with Omicron compared to 18.3 percent of the Pfizer group and 20.7 percent in the Moderna group. The authors concluded that a fourth vaccination in healthy young individuals may therefore only have “marginal benefits.” On the other hand, other data out of Israel provided in a preprint server in February showed that a fourth dose did appear to provide additional protection against infection and severe illness in patients 60 and older.
Given the published data discussed above, it does seem likely that the F.D.A. and C.D.C. will approve at least some version of these requests, although it is still uncertain how quickly that will occur and precisely for which populations. A number of infectious disease, immunology, and public health experts in the United States have opined recently that the benefit of a fourth dose is not as clear and that therefore our attention would be better focused on increasing vaccination in unvaccinated populations, both here in the United States and abroad. Moreover, timing of a fourth dose may be tricky to ascertain, as noted in a recent article in The New York Times by Knvul Sheikh, because protection would optimally be acquired as soon as possible before any next surge in cases occurs.
And right now, it’s just not clear when that will be locally.
While on the one hand, such uncertainty regarding the need for a second booster dose may bring some anxiety and concern, I am encouraging my patients instead to try and focus on the incredible speed with which these vaccines have been developed and distributed, as well as the many opportunities locally for rolling out booster doses when they have been called for.
Whatever the next steps in this pandemic, I remain confident that the hard work of the scientists and physicians across the world who have dedicated the last two years of their lives to this effort will not waver or falter at this late point. Every day we have more and more tools available to fight Covid-19, and that is one thing we can all be grateful for.
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Joshua Potter, D.O., a physician with Stony Brook Southampton Hospital’s Meeting House Lane Medical Practice, oversees the practice’s Shelter Island office. He specializes in family and neuromusculoskeletal medicine. Opinions expressed in this column are his personal and professional views and not necessarily those of his employer.
