Does the BCG Vaccine Protect against COVID19?

One of the beneficial oddities of the BCG vaccine that sets it apart from other attenuated antigens is the broad risk reduction its recipients have experienced against pathogens other than the mycobacteria that cause tuberculosis. The first indication of broad protection was found several years after it was first administered in a non-specific 4x reduction in child mortality rates. Subsequent epidemiological research over the past century has revealed broad risk reduction against respiratory tract infections from other viral and bacterial pathogens as well as parasitic diseases like malaria. During the course of the pandemic, an association between neonatal BCG vaccination and lower COVID19 mortality emerged in the global south inspiring two double blind, placebo controlled RCTs in the U.S. where almost no one is inoculated against tuberculosis.

A Phase II double-blinded, placebo-controlled RCT conducted among type 1 diabetes patients enrolled in a parallel clinical trial (n = 144) over 15 months in the U.S. found that 3 doses of the BCG vaccine administered over a two year period preceding the pandemic had a 92% efficacy against COVID19 with 12.5% of the placebo group contracting SARS-COV-2 compared to only 1% of BCG recipients.

A Phase III, double-blinded placebo-controlled RCT conducted among type I diabetes patients (n = 141) ,with no prior immunization against tuberculosis, over 19 months in the U.S. found that 5-6 doses of the BCG vaccine had a 43.2% efficacy against COVID19 with 41.7% of placebo recipients contracting SARS-COV-2 compared to 23.7% of vaccine recipients. The BCG vaccine efficacy was 52.1% against the more transmissible omicron variants during the study and about half of that against pre-omicron variants circulating in early 2021 when the trial began.

Although the relative risk reduction was more than twice as large in phase II trial than the phase III trial the absolute risk reduction was >1.5x larger in the phase III trial (18%) than the phase II trial (11.5%) so the BCG vaccine became more effective over time even with the more transmissible omicron variant. Over the full 34 months of both RCTs, the BCG vaccine had an efficacy 54.3% against COVID19 and an absolute risk reduction of 14.9%. Over 80% of the placebo group was vaxxed in the phase III RCT.