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Background: Little is known on the relative influence of demographic, behavioural, and vaccine-related factors on risk of post-vaccination SARS-CoV-2 infection. Aim(s): To determine risk factors for SARS-CoV-2 infection after primary and booster vaccinations. Method(s): We did a prospective population-based study in SARS-CoV-2-vaccinated UK adults, including data up to Feb 3, 2022. We built two Cox regression models to explore associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and incident SARS-CoV-2 infection after a primary course of vaccination and after a booster dose. Finding(s): 1017 (6.4%) of 15,804 fully vaccinated participants and 697 (6.1%) of 11,382 boosted participants reported breakthrough SARS-CoV-2 infection. A primary course of ChAdOx1 nCoV-19 (ChAdOx1) vs BNT162b2 was associated with higher risk of post-primary infection (adjusted HR 1.61, 95% CI 1.39-1.87). This effect remained after an mRNA booster dose (1.24 [1.04-1.49] for ChAdOx1 + BNT162b2 and 1.44 [1.07-1.92] for ChAdOx1 + mRNA1273, vs BNT162b2 + BNT162b2). Older age was associated with lower risk of infection after primary (0.96 [0.96- 0.97] per year) and booster (0.97 [0.96-0.98]) vaccinations, while lower educational level (1.71 [1.38-2.12] post primary and 1.47 [1.11-1.95] post booster for primary/secondary vs postgraduate) and at least three weekly visits to indoor public places (1.37 [1.15-1.64] post primary and 1.54 [1.21-1.96] post booster vs no visits) were associated with higher risk. Conclusion(s): Vaccine type, socioeconomic status, and behaviours affect risk of breakthrough SARS-CoV-2 infection following a primary schedule and a booster dose.
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Background: A robust correlate of vaccine-induced protection against SARS-CoV-2 infection has yet to be found. Aim(s): To explore whether post-vaccination combined IgG, IgA, and IgM responses to the SARS-CoV-2 trimeric spike glycoprotein (anti-S IgGAM) can predict protection against breakthrough SARS-CoV-2 infection. Method(s): In this prospective population-based study, we used dried blood spots to determine post-vaccination anti-S IgGAM responses in SARS-CoV-2-vaccinated UK adults. Using receiver operating characteristic (ROC) curve analysis, we assessed the ability of anti-S IgGAM titres (adjusted for days since vaccination) to predict postvaccination incident SARS-CoV-2 infection. After adjusting for household and behavioural factors reflecting risk of SARS-CoV-2 exposure, we compared the area under the ROC curve (AUROC) between minimally and fully adjusted models. Finding(s): Between Jan 12, 2021, and Jan 31, 2022, 300 (4.0%) of 7530 participants reported a breakthrough SARS-CoV-2 infection during 18 weeks of follow-up (220 [4.4%] ChAdOx1 nCoV-19 [ChadOx1] recipients and 75 [3.1%] BNT162b2 recipients). Anti-S IgGAM titres were modestly predictive of breakthrough infection (overall: AUROC 0.582 [95% CI 0.550-0.614];ChAdOx1: 0.564 [0.526-0.602];BNT162b2: 0.562 [0.488-0.636]). Adjustment for exposure factors significantly improved discrimination (overall: 0.666 [0.633-0.699], p<0.0001;ChAdOx1: 0.656 [0.617-0.695], p<0.0001;BNT162b1: 0.709 [0.649-0.769], p=0.0012). Conclusion(s): Anti-S IgGAM titres correlate with protection against SARS-CoV-2 infection in vaccinated adults, but exposure factors contribute significantly to risk.
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Background: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. Aim(s): To study factors associated with SARS-CoV-2 seropositivity. Method(s): We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited from May to November 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. Result(s): 1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with higher risk of seropositivity included frontline health/care occupation (adjusted OR 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, Ptrend=0.01), BMI >=25 vs <25 kg/m2 (1.24, 1.11-1.39), South Asian vs White ethnicity (1.65, 1.10-2.49), alcohol consumption >=15 vs 0 units/week (1.23, 1.04-1.46), sex hormone therapy (1.25, 1.02-1.52), and use of vitamin D supplements (1.16, 1.03-1.30). Postgraduate degree (vs primary or secondary level: 0.82, 0.67-0.99), light physical exercise (0.80, 0.70-0.93, for >=10 vs 0-4 h/week), passive smoking (0.59, 0.37-0.95), and prescribed paracetamol use (0.70, 0.52-0.96) were independently associated with lower risk. Conclusion(s): Our findings confirm ethnic, occupational, and lifestyle determinants of SARS-CoV-2 seropositivity and identify additional risk factors.
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Background: Antibody responses to SARS-CoV-2 vaccines vary for reasons that are poorly understood. AIM: To determine factors modifying antibody responses to SARS-CoV-2 vaccination. Method(s): We tested for anti-Spike (S) antibodies before and after 2 doses of ChAdOx1 or BNT162b2 given to UK adults December 2020-July 2021. Participant characteristics and outcomes were captured by online questionnaires. Logistic regression was used to estimate odds of seronegativity after vaccination. For those who were seronegative after 2 vaccine doses, repeat testing was offered following a booster dose of BNT162b2 or mRNA-1273. Result(s): Anti-S antibodies were undetectable in 378/9101 (4.2%) participants after 2 vaccine doses. Increased risk of post-vaccination seronegativity associated with administration of ChAdOx1 vs BNT162b2 (aOR 7.0, 95% CI 4.411.2), shorter interval between vaccine doses (aOR 1.6, 1.2-2.1, 6-10 vs >10 weeks), poor vs excellent general health (aOR 3.3, 1.5-7.5), immunodeficiency (aOR 6.8, 2.6-17.4) and immunosuppressant use (aOR 3.8, 2.4-5.8). Odds of seronegativity were lower for participants who were SARS-CoV-2 seropositive pre-vaccination (aOR 0.2, 0.0-0.7) and for those taking vitamin D supplements (aOR 0.7, 0.5-0.9). Of 247 participants who were seronegative following 2 vaccine doses, 8 (3.2%) remained seronegative post-booster: all were immunosuppressed. Conclusion(s): We identify multiple determinants of antibody responses to SARS-CoV-2 vaccines, many of which are modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount anti-S responses following two doses of ChAdOx1 or BNT162b2.
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Introduction and ObjectivesLittle is known about how demographic, behavioural, and vaccine-related factors affect risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations.MethodsThis prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT1262b2) and those who received a booster dose (BNT1262b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence and testing behaviours.Results1051 (7.1%) of 14,713 post-primary participants and 1009 (9.4%) of 10,665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195–216) and 85 days (66–103), respectively. Primary vaccination with ChAdOx1 (vs BNT182b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1.63, 95% CI 1.41–1.88) and after an mRNA-1273 booster (1.26 [1.00–1.57] vs BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0.97 [0.96–0.97] per year;post-booster: 0.97 [0.97–0.98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1.78 [1.44–2.20] for primary or secondary vs postgraduate;post-booster: 1.46 [1.16–1.83]) and at least three weekly visits to indoor public places (post-primary: 1.36 [1.13–1.63] vs none;post-booster: 1.29 [1.07–1.56]).ConclusionsVaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations. These findings can inform public health messaging and prioritisation for future vaccinations.Please refer to page A208 for declarations of interest related to this .
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IntroductionVitamin D deficiency associates with susceptibility to COVID-19 and other acute respiratory infections (ARI).ObjectiveTo determine whether a ‘test-and-treat’ approach to vitamin D replacement in the general population reduces incidence of COVID-19 or other ARI.MethodsWe randomly assigned 6200 UK adults to receive an offer of a postal vitamin D test with postal provision of a 6-month supply of higher-dose vitamin D (3200 IU/d, n=1550) or lower-dose vitamin D (800 IU/d, n=1550) to those with 25(OH)D <75 nmol/L vs no offer of vitamin D testing or supplementation (n=3100). The primary outcome was the proportion of participants experiencing at least one test- or doctor-confirmed ARI of any cause at 6 months. Secondary outcomes included incidence of COVID-19.Results2958/3100 adults randomised to intervention accepted the offer of testing, of whom 2690 (90.9%) had 25(OH)D <75 nmol/L and received vitamin D supplements (1356 higher-dose, 1334 lower-dose). 72 adults in the higher-dose offer group, 86 in the lower-dose offer group and 132 in the no offer group experienced at least one ARI of any cause during follow-up (odds ratio [OR] for higher-dose vs. no offer 1.05, 95% CI 0.78–1.40;OR for lower-dose vs. no offer 1.27, 0.96–1.68). COVID-19 was diagnosed in 32 adults in the higher-dose offer group, 48 in the lower-dose offer group and 68 in the no offer group (OR for higher-dose vs. no offer 0.90, 0.59–1.37;OR for lower-dose vs. no offer 1.37, 0.94–1.99).ConclusionsIn adults with a high baseline prevalence of vitamin D insufficiency, a test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or COVID-19.Please refer to page A209 for declarations of interest related to this .
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Background: A 2017 meta-analysis of data from 10,933 participants in 25 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARI) revealed a protective effect. Since then, data from 15 new RCTs with over 20,000 participants have emerged. Methods: Systematic review and meta-analysis of data from RCTs of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard RCT Number (ISRCTN) registry from inception to 1st May 2020. Findings We identified 40 eligible RCTs (total 30,956 participants, aged 0 to 95 years). Data were obtained for 29,841 (96.5%) of 30,909 participants in 39 studies. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced ARI risk overall (Odds Ratio [OR] 0.89, 95% CI 0.81 to 0.98;P for heterogeneity 0.009). No statistically significant effect of vitamin D was seen for sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials using a daily dosing regimen (Table presented) (OR 0.75, 95% CI 0.61 to 0.93);at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89);and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.94). Vitamin D did not influence the risk of experiencing a serious adverse event. Risk of bias within studies was assessed as being low for all but two trials. A funnel plot showed asymmetry, suggesting that small trials showing non-protective effects of vitamin D may have been omitted from the meta-analysis. Interpretation: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of heterogeneity across trials. The overall effect size may have been over-estimated due to publication bias. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation.