The COVID-19 pandemic challenges available hospital capacity. This is augmented by absenteeism of healthcare workers (HCW). Strategies to protect HCW are therefore highly needed.
Bacille Calmette-Guérin (BCG) has protective non-specific effects against other infections; a plausible immunological mechanism is identified in terms of “trained innate immunity”. Trials to study if BCG can reduce the incidence and/or severity of COVID-19 have therefore been initiated all over the world. But studies in Africa are also needed. In this trial, the primary objective is to test whether BCG vaccine can be used to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. Secondary, we will investigate whether BCG vaccine can reduce the number of HCW infected with COVID-19 and whether BCG reduces hospital admissions due to illness of HCW during the COVID-19 pandemic. We furthermore aim to improve the capacity for clinical research in the consortium countries by conducting several training courses.
Our main hypothesis is that BCG vaccination of HCW reduces absenteeism due to illness of HCW by 20%. To test the hypothesis, we will carry out a single-blind placebo-controlled multi-center block randomized trial including a total of 1050 HCW. The trial will take place in Mozambique, conducted by the Manhiça Health Research Centre (CISM) and in Guinea-Bissau, conducted by the Bandim Health Project. In both countries, eligible participants will be recruited from various hospitals and health centres, pending approval from each institution. The aim is to recruit 525 HCW into the trial at both sites. Originally, the trial was meant to also be conducted at Cape Verde (with 350 HCW enrolled at each site), but since no legal framework existed for the conduct of randomized trials at the time, this was not possible. We hope, however, that our initiative and contact with the ethical committee might bring about change to this regard. In place of the RCT at Cape Verde, an observational study among 400 participants to assess factors associated with transmission and dynamics of SARS-CoV-2 infection among HCW will be conducted on the Cape Verde islands.
For the RCT in Mozambique and Guinea-Bissau, HCW ≥18 years (nurses/physicians/others) are eligible for participation. Exclusion criteria are allergy or previous adverse events to BCG; previous/active infection with M. tuberculosis; fever (>38 C) within past 24 hours; suspicion of active viral/bacterial infection; history of frequent infections or other symptoms of being immunocompromised; pregnancy; not having a mobile phone. Interested participants that have been COVID-19 vaccinated can participate in the trial, if >14 days have passed since the second dose was administered.
Participants will be block randomized by country, occupation, and sex 1:1 to intradermal standard dose of BCG vaccine or placebo (saline). The primary endpoint is days of absenteeism due to illness. Secondary endpoints are days of absenteeism because of documented COVID infection and cumulative incidence of hospitalizations due to illness. At enrolment, data on chronic illnesses/treatment, lifestyle (family structure, socioeconomic factors, smoking), previous BCG immunization and other vaccination history will be collected and a blood sample for SARS-CoV-2 serology will be obtained.
Participants are followed with biweekly mobile phone interviews regarding symptoms/absenteeism and cause, and COVID testing if done. In the statistical analysis we will assess the effect of BCG vaccination vs. placebo on endpoints; monthly interim analyses are conducted to allow results to inform policy making during the ongoing epidemic. The trial receives oversight from an internationally composed Data Safety Monitoring Board which receives monthly reports on the progress of the trial, which was approved by the Guinea-Bissau and Mozambican ethical committees and received consultative approval by the Danish ethical committee. If BCG can reduce the impact of COVID-19 among HCW it has global ramifications, since the intervention can quickly be scaled up and provided worldwide to at-risk populations.