BCG vaccination history associates with decreased SARS-CoV-2 seroprevalence across a diverse cohort of health care workers

J Clin Invest. 2021 Jan 19;131(2):e145157. doi: 10.1172/JCI145157.


BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 1 million deaths worldwide; thus, there is an urgent need to develop preventive and therapeutic strategies. The antituberculosis vaccine bacillus Calmette-Guérin (BCG) demonstrates nonspecific, protective innate immune-boosting effects. Here, we determined whether a history of BCG vaccination was associated with decreased SARS-CoV-2 infection and seroconversion in a longitudinal, retrospective observational study of a diverse cohort of health care workers (HCWs).METHODSWe assessed SARS-CoV-2 seroprevalence and collected medical questionnaires, which included information on BCG vaccination status and preexisting demographic and clinical characteristics, from an observational cohort of HCWs in a multisite Los Angeles health care organization. We used multivariate analysis to determine whether a history of BCG vaccination was associated with decreased rates of SARS-CoV-2 infection and seroconversion.RESULTSOf the 6201 HCWs, 29.6% reported a history of BCG vaccination, whereas 68.9% had not received BCG vaccination. Seroprevalence of anti-SARS-CoV-2 IgG as well as the incidence of self-reported clinical symptoms associated with coronavirus disease 2019 (COVID-19) were markedly decreased among HCWs with a history of BCG vaccination compared with those without BCG vaccination. After adjusting for age and sex, we found that a history of BCG vaccination, but not meningococcal, pneumococcal, or influenza vaccination, was associated with decreased SARS-CoV-2 IgG seroconversion.CONCLUSIONSA history of BCG vaccination was associated with a decrease in the seroprevalence of anti-SARS-CoV-2 IgG and a lower number of participants who self-reported experiencing COVID-19-related clinical symptoms in this cohort of HCWs. Therefore, large randomized, prospective clinical trials of BCG vaccination are urgently needed to confirm whether BCG vaccination can confer a protective effect against SARS-CoV-2 infection.

Keywords: COVID-19; Innate immunity; Vaccines.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • BCG Vaccine / immunology*
  • BCG Vaccine / pharmacology
  • COVID-19 / epidemiology*
  • COVID-19 / immunology*
  • COVID-19 / prevention & control
  • Cohort Studies
  • Female
  • Health Personnel*
  • Humans
  • Immunity, Innate
  • Influenza Vaccines / immunology
  • Influenza Vaccines / pharmacology
  • Longitudinal Studies
  • Los Angeles / epidemiology
  • Male
  • Meningococcal Vaccines / immunology
  • Meningococcal Vaccines / pharmacology
  • Middle Aged
  • Multivariate Analysis
  • Pneumococcal Vaccines / immunology
  • Pneumococcal Vaccines / pharmacology
  • Retrospective Studies
  • Seroepidemiologic Studies


  • BCG Vaccine
  • Influenza Vaccines
  • Meningococcal Vaccines
  • Pneumococcal Vaccines