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
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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.
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SciScore for 10.1101/2022.03.24.22272835: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our analysis is subject to a number of limitations. First, in order to provide timely evidence of the effectiveness of a fourth dose of BNT162b2b vaccine, we were only able to include 10 weeks of data. Although the pattern of a short-term increase in …
SciScore for 10.1101/2022.03.24.22272835: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our analysis is subject to a number of limitations. First, in order to provide timely evidence of the effectiveness of a fourth dose of BNT162b2b vaccine, we were only able to include 10 weeks of data. Although the pattern of a short-term increase in protection against infection followed by waning is already present, long-term effectiveness needs to be evaluated. This is particularly important for estimates of effectiveness of the fourth dose against severe disease. It has been previously demonstrated that protection from previous doses against severe disease wanes more slowly compared to waning of protection against infection.20,26 Nonetheless, our study suggests a more rapid waning of protection against infection from a fourth dose compared to previous doses; therefore, waning of effectiveness against COVID-19-associated hospitalization and mortality needs to be further examined over a longer period. A second inherent limitation stems from the varying dominance of different SARS-CoV-2 variants over time. The post-fourth dose period in Israel has been dominated by the Omicron variant, which renders it difficult to assess the relative effectiveness of the fourth dose against other variants, a well-recognized limitation of real-world analyses during this pandemic.6,27,28 Furthermore, as the eligible population for a fourth dose was comprised of individuals aged 60 or older, we cannot infer effectiveness and potential waning in younger persons. Additionally, the fourth-dose rec...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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