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

Abstract

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.

Figure 1. Flow chart of this retrospective observational study.

A total of 6679 HCWs were recruited in this study. Self-reported information about a previous COVID-19 diagnosis, a positive or negative SARS-CoV-2 RT-PCR test, experience of COVID-19–related symptoms, as well as BCG, meningococcal, Pneumovax, and influenza vaccination status were collected retrospectively with an electronic survey. Among the 6679 participants, 478 did not provide a blood sample to measure the anti–SARS-CoV-2 IgG index and were thus excluded from the analysis. Of the remaining 6201 participants, 1836 reported a previous history of BCG vaccination, 1842 reported a previous meningococcal vaccination, 1007 reported receiving a Pneumovax vaccination, and 6014 reported receiving an influenza vaccination.

Figure 2. History of BCG vaccination is associated with fewer reports of COVID-19–related symptoms and decreased SARS-CoV-2 infection.

(A) Percentage of participants in the cohort of HCWs (n = 6201) with a positive anti–SARS-CoV-2 IgG test. (B) Percentage of individuals in the whole cohort who reported a history of BCG vaccination (n = 1836) or absence of a BCG vaccination (n = 4275). (C) Age (mean) of the participants reporting a previous history of BCG vaccination or no BCG vaccination. (D) Percentage of participants with or without a history of BCG vaccination who reported an absence of COVID-19–related symptoms. (E) Percentage of individuals with or without a history of BCG vaccination who self-reported experiencing COVID-19–related symptoms during the preceding 6 months. (F) Percentage of participants with or without a history of BCG vaccination who self-reported a previous COVID-19 diagnosis from a MD or RT-PCR test. (G) Percentage of participants with or without a history of BCG vaccination who self-reported having a positive SARS-CoV-2 RT-PCR test. (H) Percentage of participants with or without a history of BCG vaccination with a positive anti–SARS-CoV-2 IgG test result. (I) Percentage of individuals with or without a history of BCG vaccination with a SARS-CoV-2 IgG index threshold of 0.4 or lower or higher than 0.4. P < 0.05, by t test (C) or χ² test (D–I); P values are displayed in each graph.

Figure 3. Meningococcal, Pneumovax, and influenza vaccinations are not associated with a beneficial effect of reducing COVID-19–related symptoms or SARS-CoV-2 infection.

(A) Percentage of individuals in the entire cohort who reported a history of meningococcal (n = 1842), Pneumovax (n = 1007), or influenza (n = 6014) vaccination. (B) Percentage of individuals with a history of meningococcal, Pneumovax, or influenza vaccination who experienced COVID-19–related symptoms. (C) Percentage of individuals with or without a history of meningococcal, Pneumovax, or influenza vaccination who did not experience COVID-19–related symptoms during the prior 6 months. (D) Percentage of participants with or without a history of meningococcal, Pneumovax, or influenza vaccination who self-reported a medical diagnosis of COVID-19. (E) Percentage of participants with or without a history of meningococcal, Pneumovax, or influenza vaccination who self-reported a positive SARS-CoV-2 RT-PCR test. (F) Percentage of participants with or without a history of meningococcal, Pneumovax, or influenza vaccination with a positive anti–SARS-CoV-2 IgG test result. (G) Percentage of individuals with or without a history of meningococcal, Pneumovax, or influenza vaccination with a SARS-CoV-2 IgG index threshold of 0.4 or lower (left panel) or higher than 0.4. Significant P values (P < 0.05) by χ² test are displayed for each plot.