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

Abstract

Background The Bacille Calmette-Guerin (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 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. Methods 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. Results 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% Conclusions 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.

COVID-19 case management: The policy model in Morocco context

“…Indeed, a retrospective cohort study found that BCG vaccination in childhood has no protective effects against COVID-19 in adulthood[61]. Another study from Sweden concludes to the absence of any protective effect against the COVID-19 in BCG vaccinated persons during infancy[62]. Fourthly, the effectiveness and time to get an adequate worldwide immunisation by a specific future COVID-19 vaccination, and it could be mandatory for all citizens, or only international travels remain questionable [63].…”

On the relationship between BCG coverage and national COVID‐19 outcome: could ‘heterologous’ herd immunity explain why some countries are better off?

“…Such studies have suggested a strong relationship between national BCG vaccination policies and the COVID-19 disease burden in different countries [9,[14][15][16]. However, these findings are still controversial [17][18][19].…”

“…in individuals born right before and after the discontinuation of the Swedish BCG-NVP in midseventies, concluded that there was no difference in number of COVID-19 cases or COVID-19-related hospitalizations depending on BCG vaccination status in middle-aged individuals [18]. However, the observations from Sweden and Germany presented here indicate that the possible association of BCG-NVPs and nation-level mortality during the COVID-19 pandemic cannot be simply explained by protection against infection (i.e.…”

Efforts towards a COVID‐19 vaccine

“…However, there are indirect data that suggest a lack of efficacy of BCG against COVID‐19. Scientists compared rates of COVID‐19 cases, hospitalizations and death for about 1 million Swedish people born just before 1975 and just after 1975 (when routine BCG vaccination of newborns was abandoned in Sweden) and did not detect a significant difference (de Chaisemartin and de Chaisemartin, 2020). The data exclude an effect of a 45 year‐old BCG vaccination on COVID‐19, but does not exclude effects of more recent vaccination.…”