26 abril, 2022

Is a Fourth Dose of COVID-19 mRNA Vaccine Needed?

Two retrospective Israeli cohort studies suggest that, after a fourth dose of BNT162b2, participants aged ≥60 had reduced risk for infection and severe disease in the short term.

In the wake of the surging SARS-CoV-2 Omicron variant, a fourth dose of the Pfizer-BioNTech (BNT162b2) vaccine in those aged ≥60 was approved in Israel. Now, two retrospective cohort studies have evaluated its effectiveness at preventing COVID-19 outcomes. Using public health data from 1.2 million eligible adults, Bar-On et al. evaluated the incidence of severe COVID-19 (respiratory rate >30 breaths per minute, oxygen saturation <94%, or ratio of partial pressure of arterial oxygen to fraction of inspired oxygen <300) in 623,000 persons who received a fourth dose (8–14 days previously) compared with three doses (629,000 recipients) and an internal control (days 3–7 after a fourth dose). From week 4 through week 6, adjusted rates of severe disease ranged from 3.5–4.3-fold lower in the four-dose group than in the three-dose group, and from 2.3–2.8-fold lower than in the internal control group. From week 4 through week 8, adjusted rates of confirmed SARS-CoV-2 infection were 2.0–1.1-fold lower in the four-dose group than in the three-dose group and 1.8–1.0-fold lower than in the internal control.

In a second study, Magen et al. used data from an Israeli healthcare organization to match a cohort of 182,000 members aged ≥60 who received a fourth dose with those who received three doses. Between days 7 and 30 postvaccination, the relative effectiveness of a fourth versus third dose was 45% against SARS-CoV-2 infection, 55% against symptomatic COVID-19, 68% against COVID-19–related hospitalization, 62% against severe COVID-19, and 74% against COVID-19–related death.


These studies showed a modest, transient effect of a fourth dose of mRNA vaccine on infection — and possibly a larger effect on severe disease. It’s important to note that neither study was randomized, and individuals receiving a fourth dose differed from those who did not in aspects that cannot be estimated with administrative data (e.g., masking, avoiding indoor gatherings, seeking medications such as monoclonal antibodies and antivirals that prevent severe outcomes), and neither study compared the use of these highly effective measures between groups. In the hope of designing improved vaccination strategies, it’s also important to examine why a small fraction of individuals develop serious disease after two, three, or four doses of the vaccine. Frequent re-dosing of large swaths of the population is neither sustainable nor, as an editorialist points out, immunologically wise.

Créditos: Comité científico Covid

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