key: cord-0763219-6x3qopgt
authors: Zhang, J.; Teng, F.; Zhang, X.; Wang, H.; Liang, T.; Guo, S.-B.; yu, x.
title: Down-regulation of SARS-CoV-2 neutralizing antibodies in vaccinated smokers
date: 2021-12-11
journal: nan
DOI: 10.1101/2021.12.09.21267349
sha: 0f87473de3aa1f8461c22e0e87396f5b125e4c56
doc_id: 763219
cord_uid: 6x3qopgt

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.

antibodies (NAbs) following COVID-19 vaccination since smoking profoundly suppresses the adaptive immune response to pathogen infection and the association between vaccination and smoking remains unclear. The SARS-CoV-2 Spike antibodies and NAbs (days 0, 14, 42, and 90) were measured in 164 participants received two vaccine doses of an inactivated vaccine (Sinovac-CoronaVac) longitudinally. Anti-Spike antibodies was elevated 14 and 42 days after COVID-19 vaccination compared to baseline (i.e., "Day 0"). Notably, 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). 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. 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. Altogether, our results indicate that smoking is a specific risk factor for COVID-19 breakthrough infection following vaccination.

As of December 7, 2021, coronavirus disease 2019 (COVID-19) has infected more than 2.6 billion people and caused over 5 million deaths worldwide.

Vaccination is an effective approach to help control COVID-19 with 8.17 billion All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted December 11, 2021. ; https://doi.org/10.1101/2021.12.09.21267349 doi: medRxiv preprint vaccine doses thus far administered 1 . 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) 2 . 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 since smoking profoundly suppresses the adaptive immune response to pathogen infection 3, 4 . We recruited 164 participants between 20 and 58 years old from Beijing Chaoyang Hospital from December 2020 to March 2021, who were divided into smoking and nonsmoking groups (Table S1 and Supplementary Methods). The participants received two vaccine doses of an inactivated whole-virion SARS-CoV-2 vaccine (Sinovac-CoronaVac) two weeks apart (i.e., "Day 0" and "Day 14"), and their serum was collected longitudinally on days 0, 14, 42, and 90 (Table S2 ). Since the SARS-CoV-2 Spike (S) protein is required for viral entry, serological antibodies on days 0, 14, and 42 targeting Spike (S) protein and its specific domains, including subunit 1 (S1), receptor binding domain (RBD), and subunit 2 extracellular domain (S2ECD), were detected using a protein array (Supplementary Methods).

Antibody levels to S protein and domains (S1, S2ECD, RBD) were elevated 14 and 42 days after COVID-19 vaccination compared to baseline in All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted December 11, 2021. ; https://doi.org/10.1101/2021.12.09.21267349 doi: medRxiv preprint both participant groups (i.e., "Day 0"). 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) ( Figure 1A and Figures S1-S4) .

The SARS-CoV-2 Spike D614G substitution is prevalent, with data showing that it increases SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells 5 . Therefore, we measured the levels of vaccines is warranted. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted December 11, 2021. ; https://doi.org/10.1101/2021.12.09.21267349 doi: medRxiv preprint preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted December 11, 2021. ; https://doi.org/10.1101/2021.12.09.21267349 doi: medRxiv preprint pseudovirus neutralization (pNT50). All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted December 11, 2021. ; https://doi.org/10.1101/2021.12.09.21267349 doi: medRxiv preprint

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We thank all vaccine recipients for providing serum samples. We also thank Dr.Brianne Petritis for her critical review and editing of this manuscript. This study is supported by grants from the National Key R&D Program of China