Determinants of Antibody Responses to SARS-CoV-2 Vaccines: Population-Based Longitudinal Study (COVIDENCE UK).

Antibody responses to SARS-CoV-2 vaccines vary for reasons that remain poorly understood. A range of sociodemographic, behavioural, clinical, pharmacologic and nutritional factors could explain these differences. To investigate this hypothesis, we tested for presence of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies before and after 2 doses of ChAdOx1 nCoV-19 (ChAdOx1, AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine between December 2020 and July 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacologic and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Additionally, percentage differences in antibody titres between groups were estimated in the sub-set of participants who were seropositive post-vaccination using linear regression. Anti-spike antibodies were undetectable in 378/9101 (4.2%) participants at a median of 8.6 weeks post second vaccine dose. Increased risk of post-vaccination seronegativity associated with administration of ChAdOx1 vs. BNT162b2 (adjusted odds ratio (aOR) 6.6, 95% CI 4.2−10.4), shorter interval between vaccine doses (aOR 1.6, 1.2−2.1, 6−10 vs. >10 weeks), poor vs. excellent general health (aOR 3.1, 1.4−7.0), immunodeficiency (aOR 6.5, 2.5−16.6) and immunosuppressant use (aOR 3.7, 2.4−5.7). Odds of seronegativity were lower for participants who were SARS-CoV-2 seropositive pre-vaccination (aOR 0.2, 0.0−0.6) and for those taking vitamin D supplements (aOR 0.7, 0.5−0.9). Serologic responses to vaccination did not associate with time of day of vaccine administration, lifestyle factors including tobacco smoking, alcohol intake and sleep, or use of anti-pyretics for management of reactive symptoms after vaccination. In a sub-set of 8727 individuals who were seropositive post-vaccination, lower antibody titres associated with administration of ChAdOx1 vs. BNT162b2 (43.4% lower, 41.8−44.8), longer duration between second vaccine dose and sampling (12.7% lower, 8.2−16.9, for 9−16 weeks vs. 2−4 weeks), shorter interval between vaccine doses (10.4% lower, 3.7−16.7, for <6 weeks vs. >10 weeks), receiving a second vaccine dose in October−December vs. April−June (47.7% lower, 11.4−69.1), older age (3.3% lower per 10-year increase in age, 2.1−4.6), and hypertension (4.1% lower, 1.1−6.9). Higher antibody titres associated with South Asian ethnicity (16.2% higher, 3.0−31.1, vs. White ethnicity) or Mixed/Multiple/Other ethnicity (11.8% higher, 2.9−21.6, vs. White ethnicity), higher body mass index (BMI; 2.9% higher, 0.2−5.7, for BMI 25−30 vs. <25 kg/m2) and pre-vaccination seropositivity for SARS-CoV-2 (105.1% higher, 94.1−116.6, for those seropositive and experienced COVID-19 symptoms vs. those who were seronegative pre-vaccination). In conclusion, we identify multiple determinants of antibody responses to SARS-CoV-2 vaccines, many of which are modifiable.

Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT).

OBJECTIVE: To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19. DESIGN: Phase 3 open label randomised controlled trial. SETTING: United Kingdom. PARTICIPANTS: 6200 people aged ≥16 years who were not taking vitamin D supplements at baseline. INTERVENTIONS: Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months. MAIN OUTCOME MEASURES: The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat. RESULTS: Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63). CONCLUSIONS: Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04579640.

Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK).

BACKGROUND: Risk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. METHODS: We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19. RESULTS: We recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0-30.0 kg/m2 and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m2 versus BMI <25.0 kg/m2). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use. CONCLUSIONS: After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04330599).

Intake of n-3 polyunsaturated fatty acids in childhood, FADS genotype and incident asthma.

Longitudinal evidence on the relation between dietary intake of n-3 (ω-3) very-long-chain polyunsaturated fatty acids, i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mid-childhood and asthma risk is scarce. We aimed to investigate whether a higher intake of EPA and DHA from fish in childhood is associated with a lower risk of incident asthma.In the Avon Longitudinal Study of Parents and Children, dietary intakes of EPA and DHA from fish were estimated by food frequency questionnaire at 7 years of age. We used logistic regression, controlling for confounders, to analyse associations between intake of EPA and DHA (quartiles) and incidence of doctor-diagnosed asthma at age 11 or 14 years, and explored potential effect modification by a fatty acid desaturase (FADS) polymorphism (rs1535). Replication was sought in the Swedish BAMSE birth cohort.There was no evidence of association between intake of EPA plus DHA from fish and incident asthma overall (n=4543). However, when stratified by FADS genotype, the odds ratio comparing the top versus bottom quartile among the 2025 minor G allele carriers was 0.49 (95% CI 0.31-0.79; ptrend=0.006), but no inverse association was observed in the homozygous major A allele group (OR 1.43, 95% CI 0.83-2.46; ptrend=0.19) (pinteraction=0.006). This gene-nutrient interaction on incident asthma was replicated in BAMSE.In children with a common FADS variant, higher intake of EPA and DHA from fish in childhood was strongly associated with a lower risk of incident asthma up to mid-adolescence.

Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults.

Opium decreases the age at myocardial infarction and sudden cardiac death: a long- and short-term outcome evaluation.

UNLABELLED:   BACKGROUND: Opium dependence is a recognized individual and public health threat, but little is known about its association with acute myocardial infarction (AMI) or sudden cardiac death (SCD). METHODS: In a cross-sectional study followed by a one-year matched longitudinal cohort, all 569 men hospitalized with AMI in all Cardiac Care Units (CCU) of Isfahan, Iran, were recruited in a six-month period. In addition, 123 out-of-hospital deaths were included that were diagnosed as SCD at the same duration. Among those discharged alive, 126 opium dependents were matched with 126 nondependents (mostly nonusers) according to age and smoking status, and were followed for one year. Opium dependence was measured using the ICD10 criteria and Severity of Dependence Scale (SDS) questionnaire. The method was validated by morphine blood levels. Biochemical measurements, blood pressure, blood cell counts, anthropometrics, and ejection fraction were measured at baseline and repeated at the end of follow-up.  RESULTS: There were 118 (17.1%) patients with an average of 17.4 ± 10.4 years of abuse who met the criteria for opium dependency. Opium dependence decreased the age at event by 3.6 (95% CI: 1.2 - 6.0) years and was independent of smoking (P = 0.003). In terms of cardiovascular risk factors such as ejection fraction, in addition to post-AMI mortality and morbidity, no significant associations were noted at baseline or after one year of follow-up. The odds ratio of sustained smoking after AMI was 1.92 (95% CI: 1.04 - 3.52) in opium dependents (P = 0.033). CONCLUSION: Despite public opinion, opium did not improve cardiovascular risk factors, or post-AMI mortality and morbidity. Conversely, there were irrefutable findings regarding the detrimental effects of opium dependence.