BCG for Prevention of COVID-19 in Type 1 Diabetes and Other High-Risk Populations

Abstract

Miriam Davis, Grace Wolfe, Maya Vaishnaw, Willem Kuhtreiber and Denise Faustman*

Bacille-Calmette-Guerin (BCG) is a>100 year-old biological vaccine with versatile contemporary applications. It is still used worldwide to protect against tuberculosis, upper respiratory infections, and childhood mortality. Heralded as the safest vaccine ever introduced, it is given to 120 million newborns each year in developing countries. At the beginning of the COVID-19 pandemic and before introduction of COVID-19 vaccines, at least 5 randomized, double-blind, placebo-controlled trials were launched to test BCG’s efficacy against primary infection by SARS-CoV-2. One of those trials was expressly for type 1 diabetics, one of the patient populations at high-risk of morbidity and mortality from COVID-19. The trial found that multi-dose BCG was safe and 92% effective versus placebo against SARS-CoV-2 primary infection. BCG recipients also had fewer infections of any type, suggesting that the vaccine may also provide broadbased protection against future SARS-CoV-2 variants. Two other trials with a mix of high-risk patients also found BCG vaccines had about 65% effective. These trials might have found even greater efficacy had patients been observed for longer periods and after higher vaccine doses. Three clinical trials with BCG in health care workers all using the Danish BCG strain often previously vaccinated with BCG or with latent tuberculosis, showed no efficacy. The major limitation is that BCG in adults takes 1-2 years to start to take full effect in adult populations. But once benefits appear, they may last years-to-decades according to other studies. In this review, we summarize the randomized clinical trial evidence surrounding BCG’s use against COVID-19 and possible mechanistic underpinnings. We argue in support of BCG’s use in patients with type 1 diabetes, especially because they are at high-risk of breakthrough infection after COVID-19 vaccination.