Israeli study reports reduced vaccine efficacy in people with immune suppression until 14 days after the second dose

Simon Collins, HIV i-Base

Although a paper reports lower vaccine efficacy in Israel in people with immune suppression, the results are more optimistic, and increased mortality is more linked to the time points defined in the study. [1]

This is a report on real-world efficacy from a health provider in Israel covering 25% of the population. Of 2.6 million people registered, 900,000 people had received at least one dose of the Pfizer mRNA vaccine. Mean age was 47 years (SD +/–18) and just over half were women. 

The study compared rates of infection in the week after vaccination (the reference period) to those occurring from day 7 to 28 (protected period). This seems an unusual decision given that full protection is not assumed until day 14. As a result this directly skews the overall findings.

Efficacy was based on PCR testing in the subgroup of approximately 60,000 and 27,000 participants during the reference and protection periods respectively (roughly 5% and 3% of the whole cohort). In this group, 4514 infections (7.4% of those tested) occurred during the reference period compared to 728 (2.7%) during the protected period. Mean daily incidence rates of 54.8 vs 5.4 per 100,000, respectively. 

Overall efficacy was estimated at 90% (95% CI: 79% to 95%). This was 92%  (95% CI: 83% to 96%) in ages 16 to 44, 90% (95% CI: 80% to 95%) in those aged 45 to 64, 82% (95% CI: 63% to 92%) in the age groups 65 to 74 and 82% in those aged 75 and above (95% CI: 61% to 91%).

Lower efficacy (71%; 95%CI: 37% to 87%) was reported among immunosuppressed patients, defined by medical history (e.g. immune deficiencies, CKD) and history of medications and procedures (e.g. long term use of corticosteroids). Importantly, vaccine efficacy dropped to 52% (95%CI: –26% to 82%) in immunosuppressed people older than 65, with confidence intervals that crossed 1.0 showing no significant reduction in mortality from the vaccine.

So although overall mortality rates from COVID-19 were low in both groups, most cases were in people older than 75, who showed no reduction from vaccination.

By age, the 39 vs 11 COVID-19 related deaths in the reference vs control periods were 0 vs 3 (0.2%), 1 (0.7%) vs. 8 (2.4%) and 10 (9.0%) vs. 28 (11.7%) in those aged 45 to 64, 65 to 74 and >75, respectively. 

Also significant, but not discussion in the paper, most confirmed infections during the “protected” period occurred during days 7 to 14 (see Figure 1 in the paper), when the vaccine is already known to not be fully active. By day 14, daily incidence in all age groups appears to drop by another log to <0.5 per 100,000 (approximately <0.005%).


This is a difficult study to report partly because of the defined period for protection.

When looking at overall efficacy rates there is little difference from deciding whether this should be from day 7 or day 14. 

However this becomes much more important for the mortality endpoint. The decision to define the protection period from 7 rather than 14 days after the second vaccine underestimates vaccine efficacy at reducing mortality in all groups, including those with immunosuppression.

Similar results were seen in the overall analysis of the Israeli national data. Among elderly patients, out of 63/124 COVID-related deaths recorded at least 7 days after second vaccine dose occurred in days 7 to 14. However, it had only a small (yet significant) effect on VE  estimates (98.2% vs. 96.9). [2]


  1. Chodick G et al. The effectiveness of the two-dose BNT162b2 vaccine: analysis of real-world data. Clinical Infectious Diseases ciab438. DOI: 10.1093/cid/ciab438. (17 May 2021).
  2. Haas EJ et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. The Lancet. 397(10287):1819-1829. DOI: DOI: 10.1016/S0140-6736(21)00947-8. (15 May 2021).

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