Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial

Abstract

Objectives: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic.

Methods: HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919).

Results: In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78-1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72-1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99-1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication.

Conclusions: During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19.

Keywords: BCG; COVID-19; Health care workers; Randomized controlled trial; Trained immunity.

Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1

Overview of unplanned absenteeism over the duration of the study in comparison to the number of reported positive severe acute respiratory syndrome coronavirus 2 tests per day in the Netherlands. The x-axis shows the year and month, with the red and green bars showing the overall percentage of unplanned absenteeism for the placebo and Bacillus Calmette-Guérin groups on the y-axis. The numbers in the bars represent the days of unplanned absenteeism and the total workdays planned for all participants in the respective month. The above graph provides the number of positive severe acute respiratory syndrome coronavirus 2 tests per day in the Netherlands between 01-Mar-2020 and 31-Mar-2021 (source: https://ourworldindata.org/coronavirus/country/netherlands, date assessed 20 May 2022). Please note that testing was not yet widely available in the community during the first epidemic wave in the Netherlands in March/April 2020, and the figures provided in the top graph for those months are therefore not reliable.

Fig. 2

Cumulative incidences of documented COVID-19 (above) and first episode self-reported acute respiratory symptoms or fever (below). COVID-19 is defined as PCR-based or rapid antigen based detection of severe acute respiratory syndrome coronavirus 2 in a respiratory sample in combination with respiratory tract symptoms (cough dyspnoea, nasal cold, sore throat, or loss of smell or taste of any reported severity) or fever (body temperature ≥38.0 °C) in the period 7 days before and up to 14 days after the positive test. Self-reported acute respiratory symptoms are defined as the presence of cough or dyspnoea with a severity score of 2 or higher, or the presence of nasal cold or sore throat with a severity score of 3 or higher. BCG, bacillus Calmette-Guérin.