Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. In a retrospective cohort study, compared to the risk in the initial 90 days after receiving a 2nd dose, the risk for infection was significantly greater after 90 days for individuals aged 18-59, and significantly greater after 150 days for individuals aged 60 and over.

Evidence Rating Level: 2 (Good)

Although vaccination against SARS-CoV-2 has been reported as being 50-95% effective, the adaptive immune response to the virus has been shown to diminish over time. Israel was one of the first countries to launch a mass vaccination campaign, beginning in December 2020. Since June 2021 however, numbers of infected individuals have been on the rise, which may be attributed to diminishing immunity in vaccinated people. This test negative design study based in Israel examined the association between the time elapsed after a patient’s 2nd Pfizer vaccine dose and the risk of COVID-19 infection. The study population consisted of individuals who received a reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between May and September 2021, at least 3 weeks after their 2nd dose of Pfizer vaccine. Because the RT-PCR test was requested by the patients themselves, this may have generated selection bias as the study participants were likely symptomatic, required a test for travel purposes, or had other reasons for testing. Overall, there was a gradual increase in risk for COVID-19 infection, the longer the time elapsed after an individual’s 2nd vaccine dose, in comparison to the reference category of <90 days.

In-Depth [retrospective cohort]:

There were 83,057 individuals included in the pre-matched cohort, with 7973 (9.6%) having positive RT-PCR tests. Participants who previously had been infected with SARS-CoV-2 were excluded from the study, and only a participant’s 1st test result was included if multiple were done. The time after 2nd dose was categorized into 30-day intervals (after the reference category of <90 days), from 90-119, 120-149, 150-179, and >180 days. In order to account for differences in infection patterns and strains throughout the study period, a matched cohort of 37,920 individuals (taken from the pre-matched cohort) was defined with a ratio of 1:5 positive to negative individuals, for each week, age group, and demographic group. The results showed that the positive test rate in the pre-matched cohort was significantly increased in the 18-39 and 40-59 age groups after >90 days, and in the >60 age group after 150 days. In the matched cohort, when comparing to the reference of <90 days after the 2nd dose, the adjusted odds ratios were 2.37 for 90-119 days (95% CI 1.67-3.36), 2.66 for 120-149 days (95% CI 1.94-3.66), 2.82 for 150-179 days (95% CI 2.07-3.84), and 2.82 for >180 days (2.07-3.85), with p < 0.001 for all. Overall, this study demonstrated that the longer the time after one’s 2nd Pfizer dose, the greater the risk for breakthrough COVID-19 infection, at least after 90 days.

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