Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)
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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/m 2 (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/m 2 (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.
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SciScore for 10.1101/2021.11.02.21265767: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: COVIDENCE UK was sponsored by Queen Mary University of London and approved by Leicester South Research Ethics Committee (ref 20/EM/0117). Sex as a biological variable Both the minimally adjusted and fully adjusted models were controlled for age (<30 years, 30 to <40 years, 40 to <50 years, 50 to <60 years, 60 to <70 years, and ≥70 years), sex (male vs female), and duration of follow-up (days). Randomization not detected. Blinding not detected. Power Analysis Statistical analysis: The sample size required to obtain an odds ratio (OR) of at least 1.08 for a binary exposure with maximum variability (probability 0.50 changing to 0.52) and correlated with other variables in the model (R2=0.4), … SciScore for 10.1101/2021.11.02.21265767: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: COVIDENCE UK was sponsored by Queen Mary University of London and approved by Leicester South Research Ethics Committee (ref 20/EM/0117). Sex as a biological variable Both the minimally adjusted and fully adjusted models were controlled for age (<30 years, 30 to <40 years, 40 to <50 years, 50 to <60 years, 60 to <70 years, and ≥70 years), sex (male vs female), and duration of follow-up (days). Randomization not detected. Blinding not detected. Power Analysis Statistical analysis: The sample size required to obtain an odds ratio (OR) of at least 1.08 for a binary exposure with maximum variability (probability 0.50 changing to 0.52) and correlated with other variables in the model (R2=0.4), using a two-sided test with 90% power and 5% significance, was estimated as 10,964, using Stata’s powerlog program. Table 2: Resources
Antibodies Sentences Resources Semi-quantitative determination of antibody titres was done using a commercially available ELISA that measures combined IgG, IgA, and IgM (IgGAM) responses to the SARS-CoV-2 trimeric spike glycoprotein (product code MK654; The Binding Site [TBS], Birmingham, UK). IgM (IgGAMsuggested: NoneSARS-CoV-2 trimeric spike glycoproteinsuggested: NoneOutcomes: Study outcomes were presence versus absence of antibodies against SARS-CoV-2 (binary outcome assessed in all participants who did not report having tested positive for SARS-CoV-2 infection via RT-PCR or lateral flow test before enrolment), and antibody titres (continuous outcome considered in all seropositive participants). SARS-CoV-2suggested: NoneSoftware and Algorithms Sentences Resources To produce patient-level covariates for each class of medications investigated, participant responses were mapped to drug classes listed in the British National Formulary or the DrugBank and Electronic Medicines Compendium databases if not explicitly listed in the British National Formulary, as previously described. DrugBanksuggested: (DrugBank, RRID:SCR_002700)Statistical analyses were done using Stata (version 14.2; StataCorp, College Station, TX, USA). StataCorpsuggested: (Stata, RRID:SCR_012763)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study also has some limitations. First, COVIDENCE UK is a self-selected cohort, and thus several groups—such as people younger than 30 years, people of lower socioeconomic status, and non-White ethnic groups—are under-represented. This particularly affected our power to investigate outcomes for Black participants, who have been found to be at higher risk of SARS-CoV-2 infection4,5,12 and adverse outcomes22 than White people. However, insufficient representativeness in a cohort does not preclude identification of causal associations, and self-selection may result in better response to follow-up.40 Second, as we included asymptomatic infections in our titre analysis, we were not able to adjust for timing of infection onset, preventing us from capturing the effects of temporal changes in antibody responses. As 40% of our seropositive participants did not experience symptoms suggestive of COVID-19 or provide a symptom onset date, excluding them would have greatly reduced the power and generalisability of our analysis. Third, as with any observational study, we cannot exclude the possibility that some of the associations we report might be explained by residual or unmeasured confounding. For example, the finding that passive smoking but not active smoking reduces the risk of seropositivity compared with never-smokers should be treated with caution, unless a plausible protective mechanism can be found. However, we have minimised the risk of confounding by adjusting for a compre...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04330599 Recruiting Longitudinal Population-based Observational Study of COVID-1… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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