Fourth Covid Shot?

Do you need a fourth Covid booster shot? Probably not. Pfizer and Moderna have asked the FDA for authorization of a second booster, or fourth shot, for patients over 65 and all adults, respectively. The FDA reportedly will authorize, but not recommend, the fourth shot for patients over age 50.

Philip Krause and Luciana Borio, writing in The Wall Street Journal, say if your immune system is healthy, three or even two doses of these mRNA vaccines should be sufficient. Dr. Krause is a consultant to the World Health Organization and was deputy director of FDA’s Office of Vaccines Research and Review. Dr. Borio is a senior fellow for global health at the Council on Foreign Relations and was director for medical and biodefense preparedness policy at the National Security Council.

It is important to understand that vaccine-induced protection against infection is short-lived and doesn’t get much of a boost from extra shots. Yet the initial two-dose regimen is enough to provide most patients excellent protection against severe disease – mediated by durable cellular responses (B and T cells), not the neutralizing antibodies that rise and wane quickly after vaccination.

What have we learned from studies of those vaccinated?

The New York State Health Department’s large database shows the effectiveness of full vaccination (at least two mRNA doses) remained above 90% against hospitalization, including during the recent Omicron surge. Similar studies done in Sweden had the same results. Studies done in Qatar and California showed no decline in protection against severe disease with Omicron.

Those who favor more boosters point to other studies that show declining vaccine effectiveness over time, especially against Omicron. But these appear unreliable, reporting a range of results for vaccine efficacy against symptomatic disease from as high as 40% to 50% to as low as negative 40%.

To understand these numbers, it is important to know when assessing vaccine efficacy how scientists compare the rate of disease between vaccinated and unvaccinated groups. A larger difference indicates higher vaccine efficacy. But as more unvaccinated people become immune through infection (natural immunity) – especially with a highly transmissible variant such as Omicron – the gap between the groups narrows even if the vaccines are still effective.

What about studies reporting reduced rates of Omicron hospitalization in the boosted v. unboosted?

The variant’s reduced virulence means that a much smaller percentage of vaccinated people end up in the hospital – whether vaccinated or not. Those who do are likelier to have serious underlying health conditions – which may be the real reason for their hospitalization. Boosters for this population are helpful. But for immunocompetent people with one or no risk factors, two doses remain 95% effective in preventing severe Covid.

The evidence for a fourth dose booster is even less compelling. In a large Israeli study, fewer than 1 in 200 people over 60 who got Omicron ended up with severe disease after just three doses. A fourth dose reduced that likelihood even more, but the effect was driven by those with major risk factors. There’s no evidence that introducing boosters last fall had a significant impact on the course of the Omicron surge in the U.S.

In summary, if you’ve had two doses, you have a lot of protection against severe Covid disease. The same is true if you’ve been infected with the virus. If you’re over 65 or otherwise at high risk, it was reasonable to get the third shot. A fourth shot is already authorized for the severely immunocompromised, but for everyone else, the data haven’t shown meaningful benefits for the third dose, let alone a fourth.

One comment

  1. We have been in discussion about where to get the second booster. Your blog has given us the answer we needed. Thank you for helping people like us with scientific information on subjects you are well qualified to talk about. We’ll hold off.

    Comment by Allen Higginbotham on March 31, 2022 at 8:39 am