BCG vaccination in infancy does not protect against COVID-19. Evidence from a natural experiment in Sweden

TL;DR

This study uses a natural experiment in Sweden to evaluate whether BCG vaccination at birth provides protection against COVID-19, finding no significant protective effect based on large-scale cohort data and regression analysis.

Contribution

It provides the first large-scale, natural experiment-based evidence that BCG vaccination at birth does not significantly reduce COVID-19 cases or hospitalizations.

Findings

No more than 20% reduction in COVID-19 cases

No more than 24% reduction in hospitalizations

Large population data enhances estimate precision

Abstract

The Bacille Calmette-Gu\'erin (BCG) tuberculosis vaccine has immunity benefits against respiratory infections. Accordingly, it has been hypothesized that it may have a protective effect against COVID-19. Recent research found that countries with universal Bacillus Calmette-Gu\'erin (BCG) childhood vaccination policies tend to be less affected by the COVID-19 pandemic. However, such ecological studies are biased by numerous confounders. Instead, this paper takes advantage of a rare nationwide natural experiment that took place in Sweden in 1975, where discontinuation of newborns BCG vaccination led to a dramatic fall of the BCG coverage rate from 92% to 2% , thus allowing us to estimate the BCG's effect without all the biases associated with cross-country comparisons. Numbers of COVID-19 cases and hospitalizations were recorded for birth cohorts born just before and just after that change, representing 1,026,304 and 1,018,544 individuals, respectively. We used regression discontinuity to assess the effect of BCG vaccination on Covid-19 related outcomes. This method used on such a large population allows for a high precision that would be hard to achieve using a classical randomized controlled trial. The odds ratio for Covid-19 cases and Covid-19 related hospitalizations were 0.9997 (CI95: [0.8002-1.1992]) and 1.1931 (CI95: [0.7558-1.6304]), respectively. We can thus reject with 95\% confidence that universal BCG vaccination reduces the number of cases by more than 20% and the number of hospitalizations by more than 24%. While the effect of a recent vaccination must be evaluated, we provide strong evidence that receiving the BCG vaccine at birth does not have a protective effect against COVID-19.