Factors associated with anti-SARS-CoV-2 antibody titres 3 months post-vaccination with the second dose of BNT162b2 vaccine: a longitudinal observational cohort study in western Greece

Anastasia Parthymou, Evagelia E Habeos, George I Habeos, Apostolos Deligakis, Ektoras Livieratos, Markos Marangos, Dionysios V Chartoumpekis, Anastasia Parthymou, Evagelia E Habeos, George I Habeos, Apostolos Deligakis, Ektoras Livieratos, Markos Marangos, Dionysios V Chartoumpekis

Abstract

Objectives: Vaccination against SARS-CoV-2 has been extensively deployed during COVID-19 pandemic. One efficient method to evaluate response to vaccination is the assessment of humoral immunity by measuring SARS-CoV-2 antibody titres. We investigated the association between anthropometric parameters (age, body mass index), smoking, diabetes, statin use, hypertension, levels of 25(OH)D and dehydroepiandrosterone sulfate (DHEAS), and SARS-CoV-2 antibody titres after vaccination.

Design: In this longitudinal observational cohort study, 712 subjects were tested for SARS-CoV-2 antibodies 3 months after the second dose of BNT162b2 vaccine. Multiple linear regression analysis was performed to identify which factors are associated with the antibody titres.

Setting: Healthcare units of western Greece (University Hospital of Patras and "St Andrews" State General Hospital of Patras).

Participants: All adults receiving their second dose of BNT162b2 vaccine at the participating healthcare units were eligible to participate in the study. Exclusion criteria were SARS-CoV-2 infection or positive SARS-CoV-2 antibody titre at baseline. Patients who did not provide all necessary information were excluded from our analyses.

Results: We found age to be negatively associated with antibody titre (-0.005; 95% CI -0.009 to -0.001, p=0.0073), as was male gender (-0.11; 95% CI -0.1738 to -0.04617, p=0.0008). The interaction of age and gender was significant (-0.01090; 95% CI -0.01631 to -0.005490, p<0.0001), highlighting that the rate of decline in antibody titre with increasing age tends to be higher in men rather than in women. No linear trend was found between DHEAS levels and antibody titres when the lower quartile of DHEAS levels was used as reference. Tobacco use was associated with low antibody titre (-0.1097; 95% CI -0.174 to -0.046, p=0.0008) but overweight, obese or underweight subjects had similar antibody responses to normal-weight individuals. Although subjects with diabetes and hypertension had numerically lower antibody titres, this association was not statistically significant. Vitamin D levels showed no clear relationships with antibody titres.

Conclusions: Age, male gender and tobacco use are negatively associated with antibody titres after COVID-19 vaccination, but our data showed no clear correlation with vitamin D levels.

Trial registration number: NCT04954651; Results.

Keywords: COVID-19; general endocrinology; infectious diseases.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
(A) Study profile. ‘Post-vaccination’ means after the second dose of the BNT162b2 vaccine. Missing data means that patients did not provide all necessary information in the questionnaire or there was not enough sample to run all the assays. (B) SARS-CoV-2 antibody titre from 3 weeks to 3 months post-vaccination with BNT162b2. Dots indicate individual values (n=198) and straight line indicates means of log antibody titre. *p

Figure 2

(A) SARS-CoV-2 antibody titre at…

Figure 2

(A) SARS-CoV-2 antibody titre at 3 months post-vaccination plotted against age (n=712). Spearman’s…

Figure 2
(A) SARS-CoV-2 antibody titre at 3 months post-vaccination plotted against age (n=712). Spearman’s r=−0.247, p

Figure 3

(A) SARS-CoV-2 antibody titre in…

Figure 3

(A) SARS-CoV-2 antibody titre in underweight (body mass index (BMI) 30) subjects at…18.5),>

Figure 3
(A) SARS-CoV-2 antibody titre in underweight (body mass index (BMI) 30) subjects at 3 months post-vaccination. Individual values are depicted with the straight line indicating the means. (B) SARS-CoV-2 antibody titre in subjects with and without diabetes at 3 months post-vaccination. The presence of diabetes was based on the reported treatment of diabetes medication by the subjects in the questionnaires. Individual values are depicted with the straight line indicating the means.

Figure 4

(A) SARS-CoV-2 antibody titre in…

Figure 4

(A) SARS-CoV-2 antibody titre in subjects with and without hypertension at 3 months…

Figure 4
(A) SARS-CoV-2 antibody titre in subjects with and without hypertension at 3 months post-vaccination. The presence of hypertension was based on the reported treatment of antihypertensive medication by the subjects in the questionnaires. Individual values are depicted with the straight line indicating the means. (B) SARS-CoV-2 antibody titre in smoker and non-smoker subjects at 3 months post-vaccination. Individual values are depicted with the straight line indicating the means. Multiple linear regression analysis showed statistically significant negative association (p=0.0008).

Figure 5

SARS-CoV-2 antibody titre in subjects…

Figure 5

SARS-CoV-2 antibody titre in subjects with different levels of vitamin D. Individual values…

Figure 5
SARS-CoV-2 antibody titre in subjects with different levels of vitamin D. Individual values are depicted with the straight line indicating the means. Multiple linear regression analysis showed statistically significant positive association with statistically significant effect on the vitamin D levels range of 25.68–32.99 ng/mL compared with 4.1–18.89 ng/mL.
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References
    1. Polack FP, Thomas SJ, Kitchin N, et al. . Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603–15. 10.1056/NEJMoa2034577 - DOI - PMC - PubMed
    1. Hall VJ, Foulkes S, Saei A, et al. . COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study. Lancet 2021;397:1725–35. 10.1016/S0140-6736(21)00790-X - DOI - PMC - PubMed
    1. Benenson S, Oster Y, Cohen MJ, et al. . BNT162b2 mRNA Covid-19 vaccine effectiveness among health care workers. N Engl J Med 2021;384:1775–7. 10.1056/NEJMc2101951 - DOI - PMC - PubMed
    1. Chodick G, Tene L, Rotem RS, et al. . The effectiveness of the two-dose BNT162b2 vaccine: analysis of real-world data. Clin Infect Dis 2022;74:472–8. 10.1093/cid/ciab438 - DOI - PMC - PubMed
    1. Dagan N, Barda N, Kepten E, et al. . BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med 2021;384:1412–23. 10.1056/NEJMoa2101765 - DOI - PMC - PubMed
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Figure 2
Figure 2
(A) SARS-CoV-2 antibody titre at 3 months post-vaccination plotted against age (n=712). Spearman’s r=−0.247, p

Figure 3

(A) SARS-CoV-2 antibody titre in…

Figure 3

(A) SARS-CoV-2 antibody titre in underweight (body mass index (BMI) 30) subjects at…18.5),>

Figure 3
(A) SARS-CoV-2 antibody titre in underweight (body mass index (BMI) 30) subjects at 3 months post-vaccination. Individual values are depicted with the straight line indicating the means. (B) SARS-CoV-2 antibody titre in subjects with and without diabetes at 3 months post-vaccination. The presence of diabetes was based on the reported treatment of diabetes medication by the subjects in the questionnaires. Individual values are depicted with the straight line indicating the means.

Figure 4

(A) SARS-CoV-2 antibody titre in…

Figure 4

(A) SARS-CoV-2 antibody titre in subjects with and without hypertension at 3 months…

Figure 4
(A) SARS-CoV-2 antibody titre in subjects with and without hypertension at 3 months post-vaccination. The presence of hypertension was based on the reported treatment of antihypertensive medication by the subjects in the questionnaires. Individual values are depicted with the straight line indicating the means. (B) SARS-CoV-2 antibody titre in smoker and non-smoker subjects at 3 months post-vaccination. Individual values are depicted with the straight line indicating the means. Multiple linear regression analysis showed statistically significant negative association (p=0.0008).

Figure 5

SARS-CoV-2 antibody titre in subjects…

Figure 5

SARS-CoV-2 antibody titre in subjects with different levels of vitamin D. Individual values…

Figure 5
SARS-CoV-2 antibody titre in subjects with different levels of vitamin D. Individual values are depicted with the straight line indicating the means. Multiple linear regression analysis showed statistically significant positive association with statistically significant effect on the vitamin D levels range of 25.68–32.99 ng/mL compared with 4.1–18.89 ng/mL.
Figure 3
Figure 3
(A) SARS-CoV-2 antibody titre in underweight (body mass index (BMI) 30) subjects at 3 months post-vaccination. Individual values are depicted with the straight line indicating the means. (B) SARS-CoV-2 antibody titre in subjects with and without diabetes at 3 months post-vaccination. The presence of diabetes was based on the reported treatment of diabetes medication by the subjects in the questionnaires. Individual values are depicted with the straight line indicating the means.
Figure 4
Figure 4
(A) SARS-CoV-2 antibody titre in subjects with and without hypertension at 3 months post-vaccination. The presence of hypertension was based on the reported treatment of antihypertensive medication by the subjects in the questionnaires. Individual values are depicted with the straight line indicating the means. (B) SARS-CoV-2 antibody titre in smoker and non-smoker subjects at 3 months post-vaccination. Individual values are depicted with the straight line indicating the means. Multiple linear regression analysis showed statistically significant negative association (p=0.0008).
Figure 5
Figure 5
SARS-CoV-2 antibody titre in subjects with different levels of vitamin D. Individual values are depicted with the straight line indicating the means. Multiple linear regression analysis showed statistically significant positive association with statistically significant effect on the vitamin D levels range of 25.68–32.99 ng/mL compared with 4.1–18.89 ng/mL.

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