Reducing Health Care Workers Absenteeism in Covid-19 Pandemic Through BCG Vaccine

Since the beginning of 2020, SARS-CoV-2 spread rapidly throughout China and the rest of the world, with on 27 February 2020 the first detected case in the Netherlands.

According to the WHO, Health-care workers (HCW) face an elevated risk of exposure to - and infection of Covid-19.

Bacillus Calmette-Guérin (BCG) was developed as a vaccine against tuberculosis, but studies have shown its ability to induce potent protection against other infectious diseases: the so called non-specific effects (NSEs). A favorable in vitro or in vivo effect has been observed in studies for distinct viral pathogens, e.g. respiratory syncytial virus, yellow fever, herpes simplex virus; human papilloma virus.

Based on the capacity of BCG to reduce the incidence of respiratory tract infections in children, to exert antiviral effects in experimental models; and to reduce viremia in an experimental human model of viral infection, the hypothesis is that BCG vaccination induces (partial) protection against susceptibility to and/or severity of Covid-19 infection. This study evaluates the efficacy of BCG to improve the clinical course of Covid-19 infection and to prevent absenteeism in order to safeguard continuous patient care.

This randomized controlled trial has been designed as a pragmatic study with a highly feasible primary endpoint, which is unplanned absenteeism, that can be continuously measured on a bi-weekly basis). This allows for the most rapid identification of a beneficial outcome that would allow other HCWs to also benefit from the intervention if and as soon as it has been demonstrated to be effective.

Inclusion criteria

• Adult (≥18 years)
• Male or female
• Hospital personnel (expected to) taking care for patients with SARS CoV-2 infection

Exclusion criteria

• Known allergy to (components of) the BCG vaccine or serious adverse events to prior BCG administration
• Known active or latent Mycobacterium tuberculosis or with another mycobacterial species. A history with- or a suspicion of M. tuberculosis infection.
• Fever (>38 C) within the past 24 hours
• Pregnancy
• Suspicion of active viral or bacterial infection
• Vaccination in the past 4 weeks or expected vaccination during the study period, independent of the type of vaccination.
• Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) neutropenic subjects with less than 500 neutrophils/mm3; c) subjects with solid organ transplantation; d) subjects with bone marrow transplantation; e) subjects under chemotherapy; f) subjects with primary immunodeficiency; g) severe lymphopenia with less than 400 lymphocytes/mm3; h) treatment with any anti-cytokine therapies. i) treatment with oral or intravenous steroids defined as daily doses of 10mg prednisone or equivalent for longer than 3 months, or probable use of oral or intravenous steroids in the following four weeks
• Active solid or non-solid malignancy or lymphoma within the prior two years
• Direct involvement in the design or the execution of the BCG-CORONA study
• Expected absence from work of ≥4 of the following 12 weeks due to any reason (holidays, maternity leave, retirement, planned surgery etc)
• Employed to the hospital < 22 hours per week
• Not in possession of a smartphone