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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: 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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A 53 year old fit and well female was admitted to hospital with rapidly evolving progressive generalised stimulus sensitive myoclonus, axial rigidity and encephomyelitis over five days, two weeks after confirmed diagnosis of SARS-COV-2 infection. On admission to hospital she had generalised myoclonus involving face, voice, trunk, proximal and distal limbs augmented with tactile and auditory stimulus and voluntary movements. A few days later she developed significant axial rigidity, ocular bobbing and encephalitis as well as a myoclonic storm requiring intubation and ventilation. MRI Brain with contrast and CSF exami-nation were unremarkable and an EEG showed no epileptiform discharges. She was started on high dose intravenous steroids followed by 5 courses of plasma exchange. Her COVID serology was positive and other investigations including Glycine, GAD, amphiphysin and DPPX antibodies were negative. She demonstrated significant improvement and was discharged home a week after plasma exchange with the view to wean off steroids over six weeks. This case demonstrates a patient presenting with a rapidly evolving stimulus sensitive myoclonic storm with rigidity and encephalomyelitis two weeks after SARS-COV2 infection, which responded well to prompt immunomodulatory treatment.
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Introduction and Objectives Identification of modifiable risk factors for COVID-19 can inform development of public health policies to improve disease control. The COVIDENCE UK study is a population-based 5-year longitudinal study investigating risk factors for, and impacts of, COVID-19 in the UK population. Methods UK residents aged-16 years were invited via a national media campaign to participate in the COVIDENCE UK study by completion of an on-line questionnaire capturing information about potential risk factors for COVID-19. Details of potential symptoms of COVID-19 occurring since 1st February 2020 were also captured, and used to identify those who had experienced probable COVID-19 using an algorithm validated against PCR-positivity for SARS-CoV-2 infection. Multivariable logistic regression was then applied to identify factors independently associated with risk of probable COVID-19, with adjustment for fifteen potential confounders including age, sex and ethnic origin. Results A total of 9,817 participants completed the COVIDENCE UK baseline questionnaire between 1st May and 12th August 2020, of whom 982 (10.0%) were classified as having had probable COVID-19. Increased risk of probable COVID-19 was independently associated with lower household income (adjusted odds ratio [aOR] 1.52, 95% confidence interval [CI] 1.23 to 1.87), being overweight (BMI 25-30 kg/m2, aOR 1.19, 95% CI 1.01 to 1.39), poorer self-reported general health (aOR 1.33, 95% CI 1.09 to 1.61) and employment as a 'frontline worker' (aOR 1.57, 95% CI 1.34 to 1.84). Taking at least one hour of vigorous physical exercise per week was associated with a lower risk (aOR 0.77, 95% CI 0.67 to 0.89). Conclusions Lack of vigorous exercise may be a potentially modifiable risk factor for COVID-19. Lower household income, higher BMI, poorer self-reported general health and employment as a frontline worker were also independently associated with increased risk of disease.
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Introduction and ObjectivesIdentification of modifiable risk factors for COVID-19 can inform development of public health policies to improve disease control. The COVIDENCE UK study is a population-based 5-year longitudinal study investigating risk factors for, and impacts of, COVID-19 in the UK population.MethodsUK residents aged ≥16 years were invited via a national media campaign to participate in the COVIDENCE UK study by completion of an on-line questionnaire capturing information about potential risk factors for COVID-19. Details of potential symptoms of COVID-19 occurring since 1st February 2020 were also captured, and used to identify those who had experienced probable COVID-19 using an algorithm validated against PCR-positivity for SARS-CoV-2 infection. Multivariable logistic regression was then applied to identify factors independently associated with risk of probable COVID-19, with adjustment for fifteen potential confounders including age, sex and ethnic origin.ResultsA total of 9,817 participants completed the COVIDENCE UK baseline questionnaire between 1st May and 12th August 2020, of whom 982 (10.0%) were classified as having had probable COVID-19. Increased risk of probable COVID-19 was independently associated with lower household income (adjusted odds ratio [aOR] 1.52, 95% confidence interval [CI] 1.23 to 1.87), being overweight (BMI 25–30 kg/m2, aOR 1.19, 95% CI 1.01 to 1.39), poorer self-reported general health (aOR 1.33, 95% CI 1.09 to 1.61) and employment as a ‘frontline worker’ (aOR 1.57, 95% CI 1.34 to 1.84). Taking at least one hour of vigorous physical exercise per week was associated with a lower risk (aOR 0.77, 95% CI 0.67 to 0.89).ConclusionsLack of vigorous exercise may be a potentially modifiable risk factor for COVID-19. Lower household income, higher BMI, poorer self-reported general health and employment as a frontline worker were also independently associated with increased risk of disease.