Purpose: Low blood 25-hydroxyvitamin D (25(OH)D) concentration has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether baseline serum 25(OH)D concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants. Methods: UK Biobank recruited 502,624 participants aged 37–73 years between 2006 and 2010. Baseline exposure data, including serum 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and Poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection. Results: Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. 25(OH)D concentration was associated with severe COVID-19 infection and mortality univariably (mortality per 10 nmol/L 25(OH)D HR 0.92; 95% CI 0.86–0.98; p = 0.016), but not after adjustment for confounders (mortality per 10 nmol/L 25(OH)D HR 0.98; 95% CI = 0.91–1.06; p = 0.696). Vitamin D insufficiency or deficiency was also not independently associated with either COVID-19 infection or linked mortality. Conclusions: Our findings do not support a potential link between 25(OH)D concentrations and risk of severe COVID-19 infection and mortality. Randomised trials are needed to prove a beneficial role for vitamin D in the prevention of severe COVID-19 reactions or death.

Objectives: To investigate severe COVID-19 risk by occupational group. Methods: Baseline UK Biobank data (2006-10) for England were linked to SARS-CoV-2 test results from Public Health England (16 March to 26 July 2020). Included participants were employed or self-employed at baseline, alive and aged less than 65 years in 2020. Poisson regression models adjusted sequentially for baseline demographic, socioeconomic, work-related, health, and lifestyle-related risk factors to assess risk ratios (RRs) for testing positive in hospital or death due to COVID-19 by three occupational classification schemes (including Standard Occupation Classification 2000). Results: Of 120,075 participants, 271 had severe COVID-19. Relative to non-essential workers, healthcare workers (RR 7.43, 95% CI:5.52,10.00), social and education workers (RR 1.84, 95% CI:1.21,2.82) and other essential workers (RR=1.60, 95% CI:1.05,2.45) had higher risk of severe COVID-19. Using more detailed groupings, medical support staff (RR 8.70, 95% CI:4.87,15.55), social care (RR 2.46, 95% CI:1.47,4.14) and transport workers (RR= 2.20, 95% CI:1.21,4.00) had highest risk within the broader groups. Compared to white non-essential workers, non-white non-essential workers had a higher risk (RR 3.27, 95% CI: 1.90,5.62) and non-white essential workers had the highest risk (RR 8.34, 95% CI:5.17,13.47). Using SOC2000 major groups, associate professional and technical occupations, personal service occupations and plant and machine operatives had higher risk, compared to managers and senior officials. Conclusions: Essential workers have higher risk of severe COVID-19. These findings underscore the need for national and organizational policies and practices that protect and support workers with elevated risk of severe COVID-19. Trial registration -N/A: What is already known on this topic: Essential workers have a higher exposure to the SARS-CoV-2 virus due to the nature of their work. In comparison to non-essential workers, healthcare workers appear to have a higher risk of SARS-CoV-2 infection. What this study adds: Healthcare workers had a more than seven-fold higher risk of severe COVID-19; those working in social care and transport occupations had a two-fold higher risk. Adjusting for potential confounding and mediating variables did not fully account for the differences in the observed risk amongst most occupational groups. Non-white essential workers had the highest risk of severe COVID-19 infection. How might this impact on policy or clinical practice in the foreseeable future?: Our findings reinforce the need for adequate health and safety arrangements and provision of PPE, particularly in the health and social care sectors, and highlight the need for national and organizational policies and practices that protect and support workers with elevated risk of SARS-CoV-2 infection.

Evidence before this study: It is emerging that long-term symptoms are often present in people who have had acute COVID-19 disease. These symptoms affect a range of organ systems including respiratory, cardiovascular and neurological systems. It is not clear how many patients who required hospitalisation develop these symptoms and the impact they have on quality of life. We searched PubMed on 24 ^th March 2021 using the terms ‘COVID-19’, ‘long-Covid’, ‘long-term’ and ‘outcomes’. This was supplemented by hand searching relevant references and news reports. We identified several small studies focussing on specific symptoms or diseases, studies of patients in community settings and studies of patients who were hospitalised for acute COVID-19 in Italy, Russia and China. There were no peer-reviewed published data at the time of searching which captured outcomes of patients within the United Kingdom. Added Value of this study: We found that over half of patients reported not feeling fully recovered several months after onset of Covid-19 symptoms. The most common symptoms reported were fatigue, followed by breathlessness. Patients reported significant increases in new or worse disability, increases in MRC dyspnoea scale and worse quality of life as measured by EQ5D-5L summary index at the time of follow-up compared to before onset of acute COVID-19 symptoms. Our study found that women, in particular women under the age of 50 were significantly more likely to not feel fully recovered, were more breathless, more fatigued and had higher rates of new or worsened disability, even after taking severity of acute disease into account when compared to men of the same age. Implications of all available evidence: Long-term symptoms following hospitalisation for COVID-19 are very common and have significant impacts on quality of life. Women under 50 were most likely to have the worst outcomes. Policy makers need to ensure there is long-term support for people experiencing long-Covid and should plan for lasting long-term population morbidity. Funding for research to understand mechanisms underlying long-Covid and identify potential interventions for testing in randomised trials is urgently required. Structured Background: This study sought to establish the long-term effects of Covid-19 following hospitalisation. Methods: 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). Findings: 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse at follow-up (median difference 0.1 points on a scale of 0 to 1, IQR: −0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Interpretation: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females. Role of the funder: The study sponsors and funders had no role in the study design, collection, analysis, interpretation of data, writing of the report, or the decision to submit the article for publication. Investigators were independent from funders and the authors have full access to all of the data, including any statistical analysis and tables.

The risk of COVID-19 in those with chronic pain is unknown. We investigated whether self-reported chronic pain was associated with COVID-19 hospitalisation or mortality. UK Biobank recruited 502,624 participants aged 37 to 73 years between 2006 and 2010. Baseline exposure data, including chronic pain (>3 months, in at least 1 of 7 prespecified body sites) and chronic widespread pain (>3 months, all over body), were linked to COVID-19 hospitalisations or mortality. Univariable or multivariable Poisson regression analyses were performed on the association between chronic pain and COVID-19 hospitalisation and Cox regression analyses of the associations with COVID-19 mortality. Multivariable analyses adjusted incrementally for sociodemographic confounders, then lifestyle risk factors, and finally long-term condition count. Of 441,403 UK Biobank participants with complete data, 3180 (0.7%) were hospitalised for COVID-19 and 1040 (0.2%) died from COVID-19. Chronic pain was associated with hospital admission for COVID-19 even after adjustment for all covariates (incidence rate ratio 1.16; 95% confidence interval [CI] 1.08-1.24; P < 0.001), as was chronic widespread pain (incidence rate ratio 1.33; 95% CI 1.06-1.66; P = 0.012). There was clear evidence of a dose-response relationship with number of pain sites (fully adjusted global P-value < 0.001). After adjustment for all covariates, there was no association between chronic pain (HR 1.01; 95% CI 0.89-1.15; P = 0.834) but attenuated association with chronic widespread pain (HR 1.50, 95% CI 1.04-2.16, P-value = 0.032) and COVID-19 mortality. Chronic pain is associated with higher risk of hospitalisation for COVID-19, but the association with mortality is unclear. Future research is required to investigate these findings further and determine whether pain is associated with long COVID.

Socioeconomic inequality in infant mortality in the UK is rising. This study aims to identify contributory maternal and pregnancy factors that can explain the known association between area deprivation and infant mortality. A cohort study was conducted using Clinical Practice Research Datalink (CPRD) primary care data between 2004 and 2019 linked to the Index of Multiple Deprivation (IMD), and infant mortality from the Office for National Statistics death data. Potential maternal and pregnancy contributory factors included: maternal age, prior maternal health conditions, pregnancy lifestyle factors and complications, use of medications during pregnancy, and characteristics of birth. Counterfactual-based decomposition analysis was used to quantify the relative importance of equalising these factors to reduce inequalities in infant mortality. A total of 392,606 mother-child dyads were included in this study. The overall risk of infant mortality was greatest for individuals in the most deprived quintile (risk ratio 2.13 [95% CI 1.58–2.90]; risk difference 6.6 [3.8–8.8] per 10,000 live births) compared with the least deprived. Four contributory factors were identified as potentially important: preterm birth (Proportion eliminated [PE] 15.25% [95% CI 9.44–24.12%]), smoking during pregnancy (PE 13.61% [95% CI 3.96–80.97%]), maternal age <20 years at childbirth (PE 10.52% [95% CI 2.93–21.35%]) and maternal depression (PE 9.13% [95% CI 4.47–14.93%]). These collectively accounted for more than one-third of the socioeconomic inequality in mortality. Multifactorial interventions targeting maternal mental health, smoking, teenage pregnancy and preterm birth may mitigate a proportion of the effects of socioeconomic inequality but targeting these, alone, will not stem the rise in infant mortality. Structural efforts to reduce socioeconomic inequalities will also be required to prevent these excess infant deaths. 10.13039/501100000265 UK Medical Research Council , Scottish Chief Scientist Office, 10.13039/100010269 Wellcome Trust .