Abstract
BackgroundProspective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.MethodsWe 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.ResultsOf 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.ConclusionsHigher 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.
Highlights
Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking
Selected baseline characteristics of included participants are shown in Table 1. 70.1% of participants were female, and 95.7% identified their ethnicity as White, with median age of 62.3 years (IQR 52.9–68.7; Table 1)
Additional file 1: Table S3 shows factors with no evidence of association. When the former factors were included together in a fully adjusted model, we observed that South Asian ethnicity, working as a frontline worker in a health or care setting, recent travel to a place of work or study, number of public transport journeys, visits to shops and other indoor public places, travel outside of the UK, high levels of alcohol consumption (≥ 15 units per week), high body-mass index (BMI ≥ 25 kg/m2), sex hormone therapy and use of vitamin D supplements were independently associated with higher risk of SARS-CoV-2 infection as indicated by antibody seropositivity (Table 2)
Summary
Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. The vast majority of studies have been based on routine real-time reverse transcription PCR (RT-PCR) testing in healthcare settings or in the community; they are potentially open to collider bias, as the probability of being tested for infection can itself depend on the risk factors under investigation [6]. Serological population-based studies offer a different approach by testing members of a population uniformly, including people who might not be captured by routine testing. This approach reduces the risk of collider bias and can uncover previously undetected asymptomatic infections. Serology studies offer the opportunity to identify determinants of anti-SARS-CoV-2 antibody titres, which are a recognised correlate of protection against future infection [9, 10]
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