The timing of priming and booster vaccine administration varied between studies. As protocol amendments to add a booster dose took place when the trials were underway, and owing to the time taken to manufacture and release a new batch of vaccine, doses could not be administered at a 4-week interval. 1459 (53·2%) of 2741 participants in COV002 in the LD/SD group received a second dose at least 12 weeks after the first (median 84 days, IQR 77—91) and only 22 (0·8%) received a second dose within 8 weeks of the first. The median interval between doses for the SD/SD group in COV002 was 69 days (50–86). Conversely, the majority of participants in COV003 in the SD/SD group (2493 [61·0%] of 4088) received a second dose within 6 weeks of the first (median 36 days, 32–58;
appendix 1 p 11).
For our secondary analysis of cases occurring more than 21 days after the first standard dose in participants who received only standard doses, there were 192 included cases with a vaccine efficacy of 64·1% (95% CI 50·5–73·9;
table 4;
figure)
More than 21 days after their first dose, ten participants were hospitalised due to COVID-19 (defined as WHO clinical progression score ≥4), two of whom were assessed as having severe COVID-19 (WHO score ≥6), including one fatal case. All ten cases were in the control group (
table 5).
In participants who received two standard doses, efficacy against primary symptomatic COVID-19 was consistent in both the UK (60·3% efficacy) and Brazil (64·2% efficacy), indicating these results are generalisable across two diverse settings with different timings for the booster dose (with most participants in the UK receiving the booster dose more than 12 weeks after the first dose and most participants in Brazil receiving their second dose within 6 weeks of the first). Exploratory subgroup analyses included at the request of reviewers and editors also showed no significant difference in efficacy estimates when comparing those with a short time window between doses (<6 weeks) and those with longer (≥6 weeks), although further detailed exploration of the timing of doses might be warranted.