Reconcile the debate over protective effects of BCG vaccine against COVID-19

Wei Fu,Chia-Lun Liu,Shin-Yi Chou,Li-San Wang,Pei-Chuan Ho,Jonni S Moore,Nawar Nayeem,Kai-Teh Tzeng

doi:10.1038/s41598-021-87731-9

Wei Fu, Chia-Lun Liu + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-87731-9

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Abstract

While awaiting the COVID-19 vaccines, researchers have been actively exploring the effectiveness of existing vaccines against the new virus, among which the BCG vaccine (Bacillus Calmette-Guérin) receives the most attention. While many reports suggest a potential role for BCG immunization in ameliorating SARS-CoV-2 infection, these findings remain controversial. With country-level COVID-19 outbreak data from Johns Hopkins University Coronavirus Resource Center, and BCG program data from World Atlas of BCG Policies and Practices and WHO/UNICE, we estimated a dynamic model to investigate the effect of BCG vaccination across time during the pandemic. Our results reconcile these varying reports regarding protection by BCG against COVID-19 in a variety of clinical scenarios and model specifications. We observe a notable protective effect of the BCG vaccine during the early stage of the pandemic. However, we do not see any strong evidence for protection during the later stages. We also see that a higher proportion of vaccinated young population may confer some level of communal protection against the virus in the early pandemic period, even when the proportion of vaccination in the older population is low. Our results highlight that while BCG may offer some protection against COVID-19, we should be cautious in interpreting the estimated effectiveness as it may vary over time and depend on the age structure of the vaccinated population.

Highlights

The first confirmed case of COVID-19 (Coronavirus Disease 2019) was reported on January 2, 2020 in Wuhan, a metropolitan area in central China, and the causative agent of this outbreak was identified as a new strain of coronavirus, designated SARS-CoV-2
We find countries with a current bacille Calmette-Guérin (BCG) vaccination program are associated with a lower cumulative number of deaths for the second and the third month since the first reported death, while the effects are not statistically significant (Fig. 1 left)
From the earliest history of BCG vaccination as a prevention for tuberculosis, it has been observed that BCG elicits a variety of effects that impact the immune system beyond conferring specific immunity to Mycobacterium tuberculosis[31,32]

Summary

Introduction

The first confirmed case of COVID-19 (Coronavirus Disease 2019) was reported on January 2, 2020 in Wuhan, a metropolitan area in central China, and the causative agent of this outbreak was identified as a new strain of coronavirus, designated SARS-CoV-2. The COVID-19 death records in the early stages of the pandemic (up to April 22, 2020) from countries with a national BCG vaccination program to countries without, and observed significant BCG protective effect on COVID-19 mortality. We observe a notable reduction in COVID-19 mortality in countries with a national BCG vaccination program, compared to countries without such a program during the second and the third month since the first death confirmed. This echoes Escobar et al.[19] in that the protective effect of BCG vaccine, at least to some extent, existed during the early stage of the pandemic. We see that a higher proportion of vaccinated young population helps to protect the society against the virus, while the proportion of vaccinated old population seems to show limited effects

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