A fourth dose, or second booster, of Pfizer/BioNTech’s COVID-19 vaccine (Comirnaty) protected seniors living in long-term care from the most severe outcomes during the Omicron wave, despite showing a more limited effect against infection, according to prospective data from Israel.
Among over 40,000 residents, effectiveness of a fourth dose (versus a third given at least 4 months prior) was 64% and 67% against hospitalizations for either mild/moderate or severe illness, respectively, and 72% against COVID-19-related deaths, reported Khitam Muhsen, PhD, of Tel Aviv University in Israel.
The study was conducted from January to March 2022, when Omicron was the predominant strain, and protection against infection from the highly contagious variant was just 34%.
Despite initial hesitation, Israel decided in December 2021 to administer a fourth Pfizer (BNT162b2) dose to groups at higher risk for severe COVID-19 — individuals 60 and up vaccinated with their third dose at least 4 months earlier. The decision was made “with the assumption that the fourth dose was likely to boost the levels of neutralizing antibodies, which might provide cross-protection against the Omicron variant,” the group wrote in JAMA Internal Medicine.
“This study’s findings support the notion of cross-protection against the Omicron variant using the original formulation of the BNT162b2 vaccine,” they added. “Additionally, this booster might enhance protection, likely because of increasing the cross-reacting neutralizing antibody levels and enhancing cross-reactive cellular immunity against SARS-CoV-2 variants.”
The data from Muhsen and colleagues’ study were derived from 43,775 residents living in long-term facilities in Israel, 55% of whom had received a fourth dose of Pfizer’s vaccine and 45% of whom had received only a third dose at least 4 months prior. Patients in the study were an average age of 80, and just over two-thirds were women. About 60% were living in geriatric facilities. The median follow-up was 73 days.
With at least a week post-vaccination among the group receiving four doses, SARS-CoV-2 infections were detected in 4,058 individuals in the four-dose group (17.6%) and 4,370 individuals (24.9%) in the three-dose group.
Serious outcomes between the four-dose and three-dose recipients, respectively, were as follows:
- Hospitalizations for mild/moderate illness: 0.9% vs 2.8%
- Hospitalizations for severe illness: 0.5% vs 1.5%
- Deaths: 0.2% vs 0.5%
An analysis looking at the same outcomes at least 2 weeks following the fourth dose — when protection may have increased — showed largely comparable results, and a sensitivity analysis limited to residents who received most of the testing (n=26,698) also yielded similar results, with “slightly stronger point estimates,” the researchers noted.
Limitations included a lack of information on comorbidities and individuals’ reasons for not getting a fourth dose of the vaccine.
Despite these, “the results of this cohort study suggest a strong association between receipt of a fourth BNT162b2 dose with protection against COVID-19-related hospitalizations, severe disease, and deaths during the Omicron surge,” the group concluded.
Muhsen reported no conflicts. One co-author disclosed relationships with AstraZeneca/MedImmune, GlaxoSmithKline, Pfizer, MSD, and Sanofi Pasteur.