Healthcare Workers (HCWs) and non-HCWs reaction to Bacillus Calmette-Guérin (BCG) in the BATTLE trial

Healthcare workers (HCWs) may have different response to Bacillus Calmette-Guérin (BCG) vaccination due to previous occupational exposure to Mycobacterium particles. We report subgroup analysis of the BATTLE trial, comparing BCG effects in HCWs vs non-HCWs. This was a secondary analysis of a trial. The BATTLE trial was a double-blind placebo-controlled phase III clinical trial that investigated BCG revaccinating adults who were recently infected with SARS-CoV-2 virus. BCG and placebo recipients were sub-grouped based on regular occupational contact with patients into HCWs (48 BCG and 50 placebo) and non-HCWs (124 BCG and 134 placebo). Weekly COVID-19 symptom progression and injection site reactions were compared between subgroups on weeks one, two, three, and six follow-ups. HCWs were more likely to complain of itching on the injection site early after injection (OR = 2.5, p = 0.049). They developed peeling and crusting on the site of injection faster than non-HCWs (during the second week, p = 0.033 and 0.040, OR = 3.3 and 2.7, respectively). HCWs were also more likely to maintain their papule or develop a late onset pustule during later weeks (weeks four and six, p = 0.024 and 0.006, OR = 2.2 and 8.6, respectively). In terms of COVID-19 symptom progression, recovery from anosmia was more likely in the non-HCWs who received BCG (week six, pHolm’s corrected = 0.002, OR = 3.3). HCWs’ local reaction to BCG injection was slightly more rapid and more intense, possibly due to their occupational exposure. BCG may also ameliorate COVID-19 induced inflammation and anosmia in non-HCWs but not HCWs. Therefore, HCWs might be less likely to benefit from BCG vaccination. ClinicalTrials.gov register number NCT04369794.