Randomized trial of BCG in healthcare workers to reduce absenteeism during the COVID-19 pandemic in sub-Saharan Africa

Background: We tested whether providing BCG vaccine to healthcare workers (HCWs) could reduce non-planned absenteeism and thereby reduce the potential impact of the COVID-19 pandemic on healthcare systems in Africa. Methods: We conducted a multicenter, single-blinded, placebo-controlled randomized trial in Guinea-Bissau and Mozambique between December 2020 and June 2022. Participants were randomized 1:1 to BCG vaccine or placebo (saline) and followed by biweekly telephone calls for 6 mo. The incidence of unplanned absenteeism due to illness was analyzed using Bayesian negative binomial regression yielding relative RRs. Secondary outcomes included infectious disease episodes, COVID-19 infection and all-cause hospitalizations. Results: We enrolled 668 HCWs (Guinea-Bissau, n=503; Mozambique, n=165). The RR for absenteeism of BCG vs placebo was 1.29 (0.81 to 1.94) with comparable effects by country. No protection against infectious disease episodes (HR=1.18 [0.97 to 1.45]) or COVID-19 infection (HR=1.19 [0.80 to 1.75]) was observed. Two trial deaths (1 BCG, 1 control) were registered and nine admissions (3 BCG, 6 control), the all-cause admission HR being 0.51 (0.13 to 2.03). Conclusions: With 64% of the planned sample size and unplanned absenteeism rates lower than expected, BCG did not reduce self-reported absenteeism due to illness. Rather, BCG tended to increase the risk of self-reported absenteeism, infectious disease episodes and COVID-19 infections. Short summary: This was a randomized control trial assessing non-specific effects of BCG vaccination in healthcare workers. There was no beneficial effect on self-reported absenteeism due to illness within 6 mo of follow-up during the COVID-19 pandemic, but a trend towards fewer all-cause hospital admissions.