Use of heat-not-burn tobacco products, moderate alcohol drinking, and anti-SARS-CoV-2 IgG antibody titers after BNT162b2 vaccination among Japanese healthcare workers

BackgroundThe effect of heat-not-burn (HNB) tobacco product use and moderate alcohol drinking on immunogenicity to coronavirus disease (COVID-19) vaccines remain elusive. This study aimed to examine the association of tobacco product use and alcohol consumption with anti-SARS-CoV-2 spike IgG antibody titers after the BNT162b2 vaccine. MethodsParticipants were 3,457 fully vaccinated healthcare workers in the 4 national centers for advanced medical and research in Japan. Smoking status and alcohol consumption were assessed via a questionnaire, and anti-SARS-CoV-2 spike IgG titers were measured by chemiluminescent enzyme immunoassay using serum collected on the median of 64 days after the second vaccination. Multilevel linear regression models were used to estimate the geometric mean titers (GMT) and the ratios of means (RoM) between groups. ResultsOf vaccinated participants, 99.5% (3,440/3,457) were seropositive. Compared with never-smokers (GMT=119), IgG antibody titers were significantly lower among HNB tobacco users (including those who also smoked cigarettes) (GMT=105; RoM=0.88 [95%CI: 0.78-0.99]) and exclusive cigarettes smokers (GMT=96; RoM=0.81 [95%CI: 0.71-0.92]). Compared with non-drinkers of alcohol (GMT=123), alcohol drinkers consuming <1 go/day (GMT=114; RoM=0.93 [95%CI: 0.88-0.98]), 1-1.9 go/day (GMT=105; RoM=0.85 [95%CI: 0.79-0.93]), and [≥]2 go/day (GMT=101; RoM=0.82 [95%CI: 0.72-0.94]) had significantly lower antibody titers (P for trend<0.01). Spline analysis showed a large reduction of antibody until around 1 go/day of alcohol consumption, and then they gradually decreased. ConclusionsResults suggest that in addition to conventional cigarette smoking and heavy alcohol drinking, use of HNB tobacco products and moderate alcohol drinking may be predictors of lower immunological response to COVID-19 vaccine. Key MessagesO_LIEpidemiological evidence regarding the association of smoking status and alcohol drinking with COVID-19 vaccine-induced antibody levels is scarce. C_LIO_LIUsers of heat-not-burn (HNB) tobacco products, as well as cigarettes smokers, had lower antibody titers than never-smokers. C_LIO_LINot only high-dose but moderate-dose alcohol intake was also associated with decreased vaccine-induced antibody levels. C_LIO_LIHNB tobacco product use and moderate alcohol drinking may be modifiers of COVID-19 vaccine-induced immunogenicity. C_LI