Smoking and drinking alter immune response to COVID-19 vaccine

The burden of coronavirus disease 2019 (COVID-19) is expected to decrease as coverage of effective messenger ribonucleic acid (mRNA) vaccines against severe acute respiratory coronavirus 2 (SARS-CoV-2) increases.

Numerous studies demonstrate a high degree of inter-individual variability in the antibody levels induced by the vaccine. Although several factors may contribute to heterogeneity, it is essential to delineate modifiable factors affecting post-vaccination immunogenicity.

Epidemiological research on the relationship between smoking and alcohol consumption and post-vaccination antibody titers has been contradictory. There is no data associating the post-vaccination antibody response with the use of non-burning hot tobacco (HNB), which has gained popularity in the global market.

To study: Use of non-smoldering tobacco products, moderate alcohol consumption, and anti-SARS-CoV-2 IgG antibody titers after BNT162b2 vaccination in Japanese healthcare workers. Image Credit: CGN089 / Shutterstock

Smoking and excess alcohol are known to impair the activation of innate and acquired immunity and therefore reduce vaccine-induced antibody formation. As with regular cigarettes, HNB tobacco products contain nicotine, which can harm the immune system. Regarding alcohol consumption, previous studies did not assess the dose-response relationship with particular emphasis on the effect of moderate alcohol consumption. The fact is of particular concern to East Asians, especially the Japanese – who have a high rate of mutations in an alcohol-metabolizing enzyme.

A pre-printed version of the study is available on the website medRxiv* server, while the article is subject to peer review.

The study

The aim of this study was to determine the relationship between smoking (including the use of HNB tobacco) and alcohol consumption with titers of immunoglobulin (Ig) G antibodies against the SARS peak protein- CoV-2 in personnel at Japanese national medical research facilities who have received two doses of BNT162b2 vaccination.

In 2020, a joint study involving multiple centers and repeated serological surveys was launched among the employees of the six Japanese National Centers for Advanced Medicine and Research (6NC). The trial recruited 5,718 workers, of whom 5,013 reported receiving two doses of the COVID-19 vaccine (BNT162b2, Pfizer-BioNTech). Participants were divided into five categories – never smoked; former smokers (have quit smoking a cigarette and have not used HNB tobacco products); current smokers who have used only HNB tobacco products; current smokers who smoke only conventional cigarettes; and current smokers who smoke both conventional cigarettes and HNB tobacco products (dual users). In addition, the average daily alcohol consumption was assessed and subjects were divided into five groups: non-drinkers, occasional drinkers (one to three days per month) and weekly drinkers ingesting 1 go/ day, 1–1.9 go/ day, or 2 go/day 1 go of Japanese sake contains about 23 grams of ethanol).

The results

The median age of the participants was 41 years (interquartile range [IQR]: 30–50 years); 72% were women with a 0.5% history of COVID-19.

Overall, 34% of the workforce were nurses; the others were allied health professionals (18%), administrative employees (15%), physicians (14%) and researchers (13%). Almost half of the 212 current smokers used HNB tobacco products. During this time, 39% of the participants drank alcohol at least once a week. Between the second vaccination and the blood sample, the median time was 64 days. The peak anti-SARS-CoV-2 IgG antibody titers averaged 144 SU / mL with 99.5% of subjects being seropositive.

Current smokers had lower antibody titers than non-smokers. Exclusive users of HNB tobacco products and dual users had significantly lower estimated geometric means (GMTs); however, the differences were not statistically significant. The reduction reached statistical significance in a post-hoc analysis combining the two categories of HNB tobacco smokers.

Daily cigarette smokers who consumed 11 or more cigarettes per day had a greater reduction in IgG titers than those who consumed less than 11 cigarettes per day.

Dose-response association between alcohol consumption and peak anti-SARS-CoV-2 IgG titers The y-axis is the ratio of the means with the shaded area representing 95% confidence intervals
Dose-response association between alcohol consumption and peak anti-SARS-CoV-2 IgG titers = 0.02). The reference value is 0 GB / day (non drinkers). The model was adjusted for age (years, continuous), gender, job category (doctor, nurse, paramedic, administrative staff, researcher and others), body mass index (BMI) ( kg / m2, continuous), term interaction of sex and BMI, interval between second vaccination and blood collection (days, continuous), term squared the interval, history of COVID- 19, co-morbidities (diabetes, hypertension, and cancer), leisure-time physical activity (0, 1 to 59 or ≥ 60 min / week), sleep duration (

On the other hand, weekly alcoholic drinkers had significantly lower antibody titers than non-alcoholic drinkers. Additionally, peak IgG antibody titers steadily declined as alcohol consumption increased.

In addition, antibody titers were significantly lower in moderate drinkers. Spline analysis revealed a clear dose-response association with a significant decrease in the ratio of means occurring up to approximately 1 go/ day of alcohol consumption – followed by a gradual decrease with increasing alcohol consumption. However, the results may not be true in people with a diverse genetic history.

Compared to non-smokers, exclusive cigarette smokers had significantly lower peak anti-SARS-CoV-2 IgG antibody titers. Additionally, antibody titers showed a clear downward trend with increasing alcohol consumption, with significant declines seen even at low alcohol levels.

The results confirmed a deleterious effect of the use of HNB tobacco products on the immunogenicity of COVID-19 vaccination.


In conclusion, cigarette smokers and, to a lesser extent, users of HNB tobacco products had lower IgG antibody titers against the SARS-CoV-2 spike protein, after vaccination. While antibody titers consistently decreased as alcohol consumption increased, a significant low level was found even with moderate alcohol consumption.

Therefore, smoking, HNB tobacco products, and heavy drinking, and even alcohol in moderation, can alter the immunological response to COVID-19 vaccination.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.

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