COVID-19 vaccine efficacy data: solid enough to delay second dose? - Authors' reply.

We thank John Robertson and Herb Sewell for their interest in our Correspondence. We reported early rate reductions in SARS-CoV-2 infections and COVID-19 disease in health-care workers (HCWs) working at the Sheba Medical Center, Israel, receiving the BNT162b2 mRNA vaccine.

In Israel, individuals previously infected with SARS-CoV-2 were ineligible for vaccination at the time of our evaluation. Indeed, 538 (6%) of 9647 HCWs at the Sheba Medical Center were infected before vaccine roll-out and excluded from the analysis. Moreover, serology screening before receiving the first dose was offered to HCWs in our hospital. Overall, 5835 HCWs, none of whom were known to have been infected previously, were tested. 59 (1%) tested positive for antibody and consequently did not receive the vaccine. Therefore, we considered the HCW cohort included in this analysis mostly antibody-negative. Theoretically, a small proportion of HCWs could have been antibody-positive due to unrecognised past infection and were not tested before receiving the first dose; however, extrapolating from the large proportion of tested HCWs, these numbers should be negligible. Moreover, a proportion of antibody-positive people will be included in most vaccine efficacy evaluations and therefore reflect real-life settings.2, 3

We report adjusted rate reductions of 30% (95% CI 2–50) in all SARS-CoV-2 infections and of 47% (17–66) in symptomatic COVID-19 during days 1–14 after first dose of BNT162b2. Two biases should be considered in interpreting this estimate of vaccine efficacy after first dose period (days 1–4): referral bias, where symptoms developing after the first dose were attributed to vaccine adverse events and testing was postponed, and deferral bias where those who are symptomatic, recently recovered, or recently exposed might defer their vaccination and thus be under-represented in the vaccinated group. Additionally, strong evidence exists for increasing vaccine efficacy during days 7–14 after the first dose.2, 5 This interval is included in our rate reductions estimate for the 1–14 days after first dose period.

Finally, we report adjusted rate reductions of 75% (72–84) in all SARS-CoV-2 infections and 85% (71–92) in symptomatic COVID-19 during days 15–28 after the first dose of BNT162b2. Our findings are indeed from a relatively small cohort compared with more recent vaccine efficacy assessments; nonetheless, our estimates of vaccine efficacy during days 15–28 are in keeping with those found in larger cohorts: among HCW participants of the HEROES-RECOVER trial in the USA, vaccine efficacy in preventing SARS-CoV-2 infection 14 days or more after receiving the first dose of an mRNA vaccine was 80% (59–90). Among HCW participants of the SIREN study in England, vaccine efficacy against SARS-CoV-2 infection 21 days or more after receipt of the first dose was 70% (55–85). In a national assessment done in Scotland, vaccine efficacy against COVID-19 hospitalisation was 53% (45–59), 69% (62–75), and 78% (71–83) 7–13 days, 14–20 days, and 21–27 days after receipt of a first dose of BNT162b2. These data showing adequate early vaccine efficacy after a single dose of BNT162b2 should be considered when setting priority groups and optimising dosing schedules in countries facing vaccine shortages.

EL reports personal fees from Sanofi Pasteur, unrelated to this Correspondence. All other authors declare no competing interests.