Short term, relative effectiveness of four doses versus three doses of BNT162b2 vaccine in people aged 60 years and older in Israel: retrospective, test negative, case-control study

Abstract

Objective To examine the relative effectiveness of a fourth dose of the Pfizer-BioNTech mRNA (BNT162b2) vaccine compared with three vaccine doses over the span of 10 weeks. Design Retrospective, test negative, case-control study, with a matched analysis and an unmatched multiple tests analysis. Setting Nationally centralised database of Maccabi Healthcare Services, an Israeli national health fund for 2.5 million people; from 10 January 2022 (seven days after the fourth dose was first given to eligible individuals) to 13 March 2022, an omicron dominant period in Israel. Participants 97 499 Maccabi Healthcare Services members aged 60 years and older, who were eligible to receive a fourth vaccine dose and obtained at least one polymerase chain reaction (PCR) test during the study. Main outcome measures Breakthrough SARS-CoV-2 infection, defined as a positive PCR test performed seven or more days after inoculation with the BNT162b2 vaccine; and breakthrough SARS-CoV-2 infection resulting in severe covid-19 disease, defined as hospital admission or death related to covid-19. Results 27 876 participants received the fourth BNT162b2 vaccine dose and 69 623 received three doses only. Of 106 participants who died during the follow-up period, 77 had had their third doses only and 23 had had their fourth doses during the first three weeks after inoculation. In the first three weeks, a fourth dose provided additional protection against both SARS-CoV-2 infection and severe disease relative to three doses of the vaccine. However, relative vaccine effectiveness against infection quickly decreased over time, peaking during the third week at 65.1% (95% confidence interval 63.0% to 67.1%) and falling to 22.0% (4.9% to 36.1%) by the end of the 10 week follow-up period. Unlike relative effectiveness against SARS-CoV-2 infection, the relative effectiveness of a fourth dose against severe covid-19 was maintained at a high level (>72%) throughout follow-up. However, severe disease was a relatively rare event, occurring in <1% of study participants who received four doses or three doses only. Conclusions A fourth dose of the BNT162b2 vaccine appears to have provided additional protection against both SARS-CoV-2 infection and severe covid-19 disease relative to three vaccine doses. However, relative effectiveness of the fourth dose against infection appears to wane sooner than that of the third dose.

Effectiveness of a fourth dose of covid-19 mRNA vaccine against the omicron variant among long term care residents in Ontario, Canada: test negative design study

“…Recent studies in Israel among adults aged 60 years or older suggest that effectiveness of the fourth dose of BNT162b2 against infection may wane faster than the third dose, but similar to third doses, the degree of waning against severe disease is lower. 18 19 Canadian studies have found that immune protection among long term care residents wanes much faster than among younger, healthier adults after two doses; similar patterns might be expected for booster doses. 37 38 …”

“…Other jurisdictions have subsequently recommended a fourth (second booster) vaccine dose for their long term care populations. Although evidence from Israel suggests that a fourth dose compared with a third dose provides additional protection against SARS-CoV-2 infection and severe covid-19 among older adults, findings have been limited to the BNT162b2 (Comirnaty; Pfizer-BioNTech) vaccine, 18 19 and no studies to date have reported both marginal effectiveness and vaccine effectiveness of a fourth vaccine dose in long term care populations.…”

Effectiveness of a fourth dose of mRNA COVID-19 vaccine against all-cause mortality in long-term care facility residents and in the oldest old: A nationwide, retrospective cohort study in Sweden

“…Observational studies from Israel showed that in general older adults aged ≥60 years, a fourth dose of BNT162b2 was associated with lower rates of infection and severe illness 3 and had about 75% effectiveness against COVID-19 mortality compared to the third dose, during an Omicron predominant period. 4 , 5 , 6 However, all these studies were conducted in general older adults, where most were younger than 80 years and where LTCF residents were either excluded 4 or represented only 3% of the sample. 6 This means that their findings cannot be extrapolated to the most vulnerable people including the very old and those living in LTCFs, as these people may experience lower vaccine-induced protection while having a much higher risk of death.…”

“… 4 , 5 , 6 However, all these studies were conducted in general older adults, where most were younger than 80 years and where LTCF residents were either excluded 4 or represented only 3% of the sample. 6 This means that their findings cannot be extrapolated to the most vulnerable people including the very old and those living in LTCFs, as these people may experience lower vaccine-induced protection while having a much higher risk of death. 2 , 7 In addition, these previous studies covered only one to two months of follow-up, limiting the inferences with respect to durability of protection.…”

Naturally-acquired Immunity Dynamics against SARS-CoV-2 in Children and Adolescents

“…These two adjustments are the Poisson's answer to the test-negative design, where time of testing and GSA were matched. 32 Then, we calculated the rate ratio, comparing the incidence rate of time-sinceinfection to that of the SARS-CoV-2 naïve participants for each time-since-infection interval. Similarly to the primary model, the effectiveness of a previous infection at each time point, compared to SARS-CoV-2 naïve individuals, was calculated as 100%*[1-(Rate Ratio)] for each of the 3-month-since-infection intervals.…”