Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)

Abstract

Background Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. Methods We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively. Results Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48–2.33), international travel (1.20, 1.07–1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06–1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m2 (1.24, 1.11–1.39), South Asian vs. White ethnicity (1.65, 1.10–2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04–1.46). Light physical exercise associated with lower risk (0.80, 0.70–0.93, for ≥ 10 vs. 0–4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m2 (aGMR 1.10, 1.02–1.19), South Asian vs. White ethnicity (1.22, 1.04–1.44), frontline health/care occupation (1.24, 95% CI 1.11–1.39), international travel (1.11, 1.05–1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02–1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity. Conclusions Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.

Vitamin D Supplements for Prevention of COVID-19 or other Acute Respiratory Infections: a Phase 3 Randomised Controlled Trial (CORONAVIT)

“…[4][5][6] The vitamin D-inducible antimicrobial peptides cathelicidin LL-37 and human beta defensin 2 have both been shown to bind SARS-CoV-2 spike protein and inhibit binding to Angiotensin Converting Enzyme 2, its cellular receptor. 7 8 Longitudinal studies investigating potential associations between higher vitamin D status or vitamin D supplement use and reduced risk of COVID-19 or SARS-CoV-2 infection have yielded mixed results, with some reporting protective associations and others reporting null or negative associations; [9][10][11][12][13][14] meta-analyses including these and other observational studies report protective associations overall. 15 16 Findings of randomised controlled trials (RCTs) of vitamin D supplementation to prevent ARIs caused by pathogens other than SARS-CoV-2 have also been heterogeneous.…”

Cohort Profile: Longitudinal population-based study of COVID-19 in UK adults (COVIDENCE UK)

“…Asian/Asian British ethnicity was associated with increased odds both of serologically confirmed SARS-CoV-2 infection and of developing swab test-confirmed COVID-19, after rigorous adjustment for potential confounders including socioeconomic status, presence of comorbidities and multiple social and environmental factors influencing exposure to SARS-CoV-2. 7,9 Participants of Asian/Asian British origin also had higher convalescent titres of combined IgG, IgA and IgM antibodies to the SARS-CoV-2 spike protein following infection (after adjustment for multiple potential confounders including disease severity) and higher titres of the same antibodies after SARS-CoV-2 vaccination (after adjustment for multiple potential confounders including pre-vaccination anti-S titres). 9,10 Taken together, these findings highlight the need to investigate potential biological determinants of ethnic variation in susceptibility to, and severity of, COVID-19.…”

“…7,9 Participants of Asian/Asian British origin also had higher convalescent titres of combined IgG, IgA and IgM antibodies to the SARS-CoV-2 spike protein following infection (after adjustment for multiple potential confounders including disease severity) and higher titres of the same antibodies after SARS-CoV-2 vaccination (after adjustment for multiple potential confounders including pre-vaccination anti-S titres). 9,10 Taken together, these findings highlight the need to investigate potential biological determinants of ethnic variation in susceptibility to, and severity of, COVID-19.…”

“…Similarly, higher body mass index was found to associate independently with increased susceptibility to SARS-CoV-2 infection and COVID-19, and higher titres of anti-S antibodies following COVID-19 and vaccination against SARS-CoV-2. 7,9,10 The mechanisms underlying these associations are also worthy of investigation.…”

Acute and long-term impacts of COVID-19 on economic vulnerability: a population-based longitudinal study (COVIDENCE UK)

“…COVIDENCE UK is a prospective population-based cohort study of COVID-19 in the UK population. 10 Its aims are to determine risk factors for incident COVID-19 in the UK population; to characterise the natural history of COVID-19 in the UK population; to evaluate the impact of COVID-19 on the physical, mental, and economic well-being of the UK population; and to provide a resource from which to identify potential participants for future clinical trials of interventions to prevent or treat acute respiratory infections. Inclusion criteria were age ≥16 years and UK residence at the point of enrolment.…”