PREPRINT: Down-regulation of SARS-CoV-2 neutralizing antibodies in vaccinated smokers


As of December 6, 2021, coronavirus disease 2019 (COVID-19) has infected about 2.65 billion people and caused 5.26 million deaths worldwide. Vaccination is an effective approach to help control coronavirus disease 2019 (COVID-19). However, since the vaccines produce a heterogenous immune response, the risk of breakthrough infection is increased in vaccinated individuals who generate low levels of neutralizing antibodies (NAbs). It is therefore paramount in the fight against COVID-19 to identify individuals who have a higher risk of breakthrough infection despite being vaccinated. In this study, we addressed the effect of cigarette smoking on the production of NAbs following COVID-19 vaccination.We recruited 164 participants received two vaccine doses of an inactivated whole-virion SARS-CoV-2 vaccine (Sinovac-CoronaVac) two weeks apart (i.e., Day0 and Day14), which were divided into smoking and nonsmoking groups. The longitudinal changes (0, 14, 42, 90 days) of anti-Spike (S) antibodies and NAbs in serum were detected using a protein array and SARS-CoV-2 pseudovirus neutralization assay with the D614G substitution, respectively.Antibody levels to S protein and domains (S1, S2ECD, RBD) were elevated 14 and 42 days after COVID-19 vaccination compared to baseline in both participant groups (i.e., Day0).Moreover, RBD antibodies showed significantly higher expression in the nonsmoking group (n=153) than the smoking (n=11) group on day 42 (p<0.0001, Student’s t-test).The NAbs continually increased after the first and second vaccine dose, peaking on day 42. NAbs titers then significantly decreased until day 90. Compared to nonsmokers, the NAb levels in smokers remained low throughout the period of testing. Notably, the median NAb titers in the smoking group was 1.40-, 1.32-, or 3.00-fold lower than that of nonsmoking group on day 14, 42, or 90, respectively. No correlation was observed between NAbs and other factors [(i.e., age, sex, body-mass index (BMI)]. Altogether, our results indicate that smoking is a specific risk factor for COVID-19 breakthrough infection following vaccination. Further investigation of smoking and how it affects NAb levels in response to COVID-19 vaccination with a larger patient cohort and other COVID-19 vaccines is warranted.

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