Background
The BCG vaccine prevents severe childhood tuberculosis (TB) and was introduced in South Africa in the 1950s. BCG is hypothesized to train the innate immune system by inducing epigenetic and functional reprogramming, thereby providing non-specific protection against infections. respiratory tract infections.
We evaluated the BCG vaccine for the reduction of morbidity and mortality due to COVID-19 in healthcare workers in South Africa.
Methods
This randomized, double-blind, placebo-controlled trial recruited healthcare workers at three facilities in the Western Cape, South Africa, unless they were unwell, pregnant, breastfeeding, immunocompromised, hypersensitive to BCG or on experimental treatment. with COVID-19.
Participants received BCG or saline intradermally (1:1) and were contacted once every 4 weeks for 1 year.
COVID-19 testing was guided by symptoms. Hospitalization, COVID-19, and respiratory tract infections were assessed with Cox proportional hazards models and time-to-event analyses, and event severity with Markovian post hoc analyses. This study is registered with ClinicalTrials.gov, NCT04379336.
Results
Between May 4 and October 23, 2020, we enrolled 1,000 healthcare workers with a median age of 39 years (IQR 30-49), 70·4% were women, 16·5% were nurses, 14·4% doctors, 48%.
5% had latent tuberculosis and 15·3% had evidence of previous exposure to SARS-CoV-2. Hospitalization for COVID-19 occurred in 15 participants (1·5%); ten (66.7%) in the BCG group and five (33.3%) in the placebo group, hazard ratio (HR) 2.0 (95% CI 0.69–5.9, p = 0.20), indicating that there is no statistically significant protection .
Similarly, BCG had no statistically significant effect on COVID-19 (p = 0.63, HR = 1.08, 95% CI: 0.82–1.42).
Two participants (0.2%) died from COVID-19 and two (0.2%) from other reasons, all in the placebo group.
Interpretation
BCG did not protect healthcare workers from SARS-CoV-2 infection or severe illness and hospitalization related to COVID-19.
Evidence before this study
A growing body of evidence suggests that BCG induces trained immunity, thereby enhancing the host response to infection by viral and bacterial pathogens and reducing morbidity and mortality. Prior BCG vaccination may have other non-specific benefits , such as reducing the incidence of lung carcinoma and modifying the course of diabetes and multiple sclerosis.
Epidemiological studies early in the pandemic suggested that a regional history of BCG vaccination may protect populations against COVID-19. A PubMed literature search on March 28, 2022, using the terms “SARS-CoV-2” or “COVID-19” and “BCG” and “efficacy,” with the filter “randomized controlled trial,” resulted in zero -reviewed publications.
Added value of this study
To our knowledge, this study is the first published randomized, controlled, double-blind trial evaluating the effect of BCG revaccination on COVID-19 morbidity. BCG revaccination failed to protect healthcare workers in South Africa from COVID-19 and hospitalization. Furthermore, BCG revaccination did not offer protection against the morbidity of respiratory tract infections, in contrast to previous studies.
Implications of all available evidence
The non-specific immune effects of BCG revaccination may be population-, age-, pathogen-, or disease-specific. We recommend that BCG not be used for the prevention or mitigation of COVID-19 outside of a clinical trial, at least until the results of other ongoing trials in different settings are known.
