Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study (preprint)

BackgroundLittle is known about the risk of Long Covid following reinfection with SARS-CoV-2. We estimated the likelihood of new-onset, self-reported Long Covid after a second SARS-CoV-2 infection, and compared to a first infection. MethodsWe included UK COVID-19 Infection Survey participants who tested positive for SARS-CoV-2 between 1 November 2021 and 8 October 2022. The primary outcome was self-reported Long Covid 12 to 20 weeks after each infection. Separate analyses were performed for those <16 years and [≥]16 years. We estimated adjusted odds ratios (aORs) for new-onset Long Covid using logistic regression, comparing second to first infections, controlling for socio-demographic characteristics and calendar date of infection, plus vaccination status in those [≥]16 years. ResultsOverall, Long Covid was reported by those [≥]16 years after 4.0% and 2.4% of first and second infections, respectively; the corresponding estimates among those <16 years were 1.0% and 0.6%. The aOR for Long Covid after second compared to first infections was 0.72 (95% confidence interval: 0.63-0.81) for those [≥]16 years and 0.93 (0.57-1.53) for those <16 years. ConclusionsThe risk of new-onset Long Covid after a second SARS-CoV-2 infection is lower than that after a first infection for those [≥]16 years, though there is no evidence of a difference in risk for those <16 years. However, there remains some risk of new-onset Long Covid after a second infection, with around 1 in 40 of those [≥]16 years and 1 in 165 of those <16 years reporting Long Covid after a second infection.

Employment outcomes of people with Long Covid symptoms: community-based cohort study (preprint)

Background: Evidence on the long-term employment consequences of SARS-CoV-2 infection is lacking. We used data from a large, community-based sample in the UK to estimate associations between Long Covid and subsequent employment outcomes. Methods: This was an observational, longitudinal study using a pre-post design. We included UK COVID-19 Infection Survey participants who completed questionnaires on Long Covid from 3 February 2021 to 30 September 2022 when they were aged 16 to 64 years and not in full-time education. We used conditional logit modelling to explore the time-varying relationship between Long Covid status [≥]12 weeks after a first test-confirmed SARS-CoV-2 infection (reference: pre-infection) and labour market inactivity (neither working nor looking for work) or workplace absence lasting [≥]4 weeks. Results: Of 206,299 included participants (mean age 45 years, 54% female, 92% white), 15% were ever inactive in the labour market and 10% were ever long-term absent during follow-up. Compared with pre-infection, inactivity was higher in participants reporting Long Covid 30 to <40 weeks (adjusted odds ratio (aOR): 1.45; 95% CI: 1.17 to 1.81) or 40 to <52 weeks (1.34; 1.05 to 1.72) post-infection. Compared with pre-infection, reporting Long Covid was also associated with increased odds of long-term absence 18 to <24 weeks (1.40; 1.04 to 1.90) and 24 to <30 weeks (1.45; 1.03 to 2.04) post-infection, but not beyond 30 weeks. Combining with official statistics on Long Covid prevalence, our estimates translate to 27,000 (95% CI: 6,000 to 47,000) working-age adults in the UK being inactive because of their Long Covid symptoms in July 2022. Conclusions: Long Covid is likely to have contributed to reduced levels of participation in the UK labour market, though it is unlikely to be the sole driver. Further research is required to quantify the contribution of other factors, such as indirect health effects of the pandemic.

High number of SARS-CoV-2 persistent infections uncovered through genetic analysis of samples from a large community-based surveillance study (preprint)

Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may act as viral reservoirs that could seed future outbreaks 1-5, give rise to highly divergent lineages 6-8, and contribute to cases with post-acute Coronavirus disease 2019 (COVID-19) sequelae (Long Covid) 9,10. However, the population prevalence of persistent infections, their viral load kinetics, and evolutionary dynamics over the course of infections remain largely unknown. We identified 381 infections lasting at least 30 days, of which 54 lasted at least 60 days. These persistently infected individuals had more than 50% higher odds of self-reporting Long Covid compared to the infected controls, and we estimate that 0.09-0.5% of SARS-CoV-2 infections can become persistent and last for at least 60 days. In nearly 70% of the persistent infections we identified, there were long periods during which there were no consensus changes in virus sequences, consistent with prolonged presence of non-replicating virus. Our findings also suggest reinfections with the same major lineage are rare and that many persistent infections are characterised by relapsing viral load dynamics. Furthermore, we found a strong signal for positive selection during persistent infections, with multiple amino acid substitutions in the Spike and ORF1ab genes emerging independently in different individuals, including mutations that are lineage-defining for SARS-CoV-2 variants, at target sites for several monoclonal antibodies, and commonly found in immunocompromised patients 11-14. This work has significant implications for understanding and characterising SARS-CoV-2 infection, epidemiology, and evolution.

Vaccine effectiveness for preventing COVID-19 hospital admission during pregnancy: a population-based cohort study in England during the Alpha and Delta waves of the SARS-CoV-2 pandemic (preprint)

Objective: To estimate vaccine effectiveness (VE) for preventing COVID-19 hospital admission in women first infected with SARS-CoV-2 during pregnancy, and assess how this compares to VE among women of reproductive age who were not pregnant when first infected. Design: Population-based cohort study using national, linked Census and administrative data. Setting: England, United Kingdom, from 8th December 2020 to 31st August 2021. Participants: 815,4777 women aged 18 to 45 years (mean age, 30.4 years) who had documented evidence of a first SARS-CoV-2 infection in NHS Test and Trace data or Hospital Episode Statistics. Main outcome measures: A hospital inpatient episode where COVID-19 was recorded as the primary diagnosis. Cox proportional hazards models, adjusted for calendar time of infection and sociodemographic factors related to vaccine uptake and risk of severe COVID-19, were used to estimate VE as the complement of the hazard ratio for COVID-19 hospital admission. Results: Compared with unvaccinated pregnant women, the adjusted rate of COVID-19 hospital admission was 76% (95% confidence interval 69% to 82%) lower for single-vaccinated pregnant women and 83% (75% to 88%) lower for double-vaccinated pregnant women. These estimates were similar to those found for non-pregnant women: 79% (76% to 81%) for single-vaccinated and 82% (80% to 83%) for double-vaccinated. Among those vaccinated more than 90 days before infection, being double-vaccinated was associated with a greater reduction in risk than being single-vaccinated. Conclusions: COVID-19 vaccination is associated with reduced rates of severe illness in pregnant women infected with SARS-CoV-2, and the reduction in risk is similar to that for non-pregnant women. Waning of vaccine effectiveness occurs more quickly after one dose of a vaccine than two doses.

Disparities in SARS-CoV-2 case rates by ethnicity, religion, measures of socio-economic position, English proficiency, and self-reported disability: cohort study of 39 million people in England during the Alpha and Delta waves (preprint)

Objective To examine socio-demographic disparities in SARS-CoV-2 case rates during the second (Alpha) and third (Delta) waves of the COVID-19 pandemic. Design Retrospective, population-based cohort study. Setting Resident population of England. Participants 39,006,194 people aged 10 years and over who were enumerated at the 2011 Census, registered with the National Health Service (NHS) and alive on 1 September 2020. Main outcome measures Testing positive for SARS-CoV-2 during the second wave (1 September 2020 to 22 May 2021) or third wave (23 May to 10 December 2021) of the pandemic. We calculated age-standardised case rates by socio-demographic characteristics and used logistic regression models to estimate adjusted odds ratios (ORs). Results During the study period, 5,767,584 individuals tested positive for SARS-CoV-2. In the second wave, the fully-adjusted odds of having a positive test, relative to the White British group, were highest for the Bangladeshi (OR: 1.88, 95% CI 1.86 to 1.90) and Pakistani (1.81, 1.79 to 1.82) ethnic groups. Relative to the Christian group, Muslim and Sikh religious groups had fully-adjusted ORs of 1.58 (1.57 to 1.59) and 1.74 (1.72 to 1.76), respectively. Greater area deprivation, disadvantaged socio-economic position, living in a care home and low English language proficiency were also associated with higher odds of having a positive test. However, the disparities between groups varied over time. Being Christian, White British, non-disabled, and from a more advantaged socio-economic position were all associated with increased odds of testing positive during the third wave. Conclusion There are large socio-demographic disparities on SARS-CoV-2 cases which have varied between different waves of the pandemic. Research is now urgently needed to understand why these disparities exist to inform policy interventions in future waves or pandemics. What is already known on this topic People with pre-existing health conditions or disability, ethnic minority groups, the elderly, some religious groups, people with low socio-economic status, and those living in deprived areas have been disproportionately affected by the COVID-19 pandemic in terms of risk of infection and adverse outcomes. What this study adds Using linked data on 39 million people in England, we found that during the second wave, COVID-19 case rates were highest among the Bangladeshi and Pakistani ethnic groups, the Muslim religious group, individuals from deprived areas and of low socio-economic position; during the third wave, being Christian, White British, non-disabled, and from a more advantaged socio-economic position were all associated with increased odds of receiving a positive test Adjusting for geographical factors, socio-demographic characteristics, and pre-pandemic health status explained some, but not all, of the excess risk When stratifying the dataset by broad age groups, the odds of receiving a positive test remained higher among the Bangladeshi and Pakistani ethnic groups aged 65 years and over during the third wave, which may partly explain the continued elevated mortality rates in these groups

Risk of COVID-19 related deaths for SARS-CoV-2 Omicron (B.1.1.529) compared with Delta (B.1.617.2) (preprint)

Objective To assess the risk of death involving COVID-19 following infection from Omicron (B.1.1.539/BA.1) relative to Delta (B.1.617.2). Design Retrospective cohort study. Setting England, UK, 1 December 2021 to 25 January 2022. Participants 1,035,163 people aged 18-100 years who tested positive for SARS-CoV-2 in the national surveillance programme, and had an infection identified as either Omicron- or Delta compatible. Main outcome measures Death involving COVID-19 as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause-specific Cox proportional hazard regression models were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, Index of Multiple Deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Additionally, we tested for interactions between variant and sex, age, vaccination status and comorbidities. Results The risk of death involving COVID-19 was 67% lower for Omicron compared to Delta and the reduction in the risk of death involving COVID-19 for Omicron compared to Delta was more pronounced in males than in females and in people under 70 years old than in people aged 70 years or over. Regardless of age, reduction of the risk of death from Omicron relative to Delta more was more pronounced in people who had received a booster than in those having received only two doses. Conclusions Our results support early work showing the relative reduction in severity of Omicron compared to Delta in terms of hospitalisation and extends this research to assess COVID-19 mortality. Our work also highlights the importance of the vaccination booster campaign, where the reduction in risk of death involving COVID-19 is most pronounced in individuals who had received a booster. What is already known on this topic The Omicron variant, which refers to the whole lineage (BA.1, BA.2, BA.3) had already been shown to be more transmissible than the Delta variant, but there is emerging evidence suggests that the risk of hospitalisation and risk of death within 28 days after a SARS-COV-2 test is lower. However, with a highly transmissible infection and high levels of population testing, definition of death within 28 days is more likely to be susceptible to misclassification bias due to asymptomatic or co-incidental infection. There is no study so far comparing the risk of COVID-19 death as identified from death certification records, with the cause of death assessed by the physician who attended the patient in the last illness. What this study adds Using data from a large cohort of COVID-19 infections that occurred in December 2021, we examined the difference in the risk COVID-19 death, as identified from death certification records, between the Delta and Omicron BA.1 variant. Our study shows that risk of death involving COVID-19 was reduced by 67% following infection with the Omicron BA.1 variant relative to the Delta variant after adjusting for a wide range of potential confounders, including vaccination status and comorbidities. Importantly, we found that the relative risk of COVID-19 mortality following Omicron versus Delta infection varied by age and sex, with lower relative risk in younger individuals and for males than females. The reduction in risk of death involving COVID-19 was also most pronounced in individuals who had received a booster.

Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study (preprint)

Background: It is unclear whether receiving two COVID-19 vaccinations before SARS-CoV-2 infection reduces the risk of developing Long Covid symptoms. We examined whether the likelihood of symptoms 12 weeks after infection differed by vaccination status. Methods: We included COVID-19 Infection Survey participants aged 18-69 years who tested positive for SARS-CoV-2 between 26 April 2020 and 30 November 2021; we excluded participants who, before their first test-confirmed infection, had suspected COVID-19 or Long Covid symptoms, or were single-vaccinated. Participants who were double-vaccinated [≥]14 days before infection were 1:1 propensity-score matched, based on socio-demographic characteristics and time from infection to follow-up for Long Covid, to those unvaccinated at time of infection. We estimated adjusted odds ratios (aOR) of Long Covid symptoms [≥]12 weeks post-infection, comparing double-vaccinated with unvaccinated (reference group) participants. Results: The study sample comprised 3,090 double-vaccinated participants (mean age 49 years, 54% female, 92% white, median follow-up from infection 96 days) and matched control participants. Long Covid symptoms were reported by 294 double-vaccinated participants (prevalence 9.5%) compared with 452 unvaccinated participants (14.6%), corresponding to an aOR for Long Covid symptoms of 0.59 (95% CI: 0.50 to 0.69). There was no evidence of heterogeneity by adenovirus vector versus messenger ribonucleic acid vaccines (p=0.25). Conclusions: COVID-19 vaccination is associated with reduced risk of Long Covid, emphasising the need for public health initiatives to increase population-level vaccine uptake. Longer follow-up is needed, as is the assessment of further vaccine doses and the Omicron variant.

Ethnic differences in COVID-19 mortality in the second and third waves of the pandemic in England during the vaccine roll-out: a retrospective, population-based cohort study (preprint)

Objectives To assess whether ethnic differences in COVID-19 mortality in England have continued into the third wave and to what extent differences in vaccination rates contributed to excess COVID-19 mortality after accounting for other risk factors. Design Cohort study of 28.8 million adults using data from the Office for National Statistics Public Health Data Asset. Setting People living in private households or communal establishments in England. Participants 28,816,020 adults (47% male) aged 30-100 years in 2020 (mean age = 56), who were present at the 2011 Census and alive on 8 December 2020. Main outcome measures Death involving COVID-19 during the second (8 December 2020 to 12 June 2021) and third wave (13 June 2021 to 1 December 2021) of the pandemic. We calculated hazard ratios (HRs) separately for males to females to summarise the association between ethnic group and death involving COVID-19 in each wave, sequentially adjusting for age, residence type, geographical factors, sociodemographic characteristics, pre-pandemic health, and vaccination status. Results Age-adjusted HRs of death involving COVID-19 were higher for most ethnic minority groups than the White British group during both waves, particularly for groups with lowest vaccination rates (Bangladeshi, Pakistani, Black African and Black Caribbean). In both waves, HRs were attenuated after adjusting for geographical factors, sociodemographic characteristics, and pre-pandemic health. Further adjusting for vaccination status substantially reduced residual HRs for Black African, Black Caribbean, and Pakistani groups in the third wave. The only groups where fully-adjusted HRs remained elevated were the Bangladeshi group (men: 2.19, 95% CI 1.72 to 2.78; women: 2.12, 95% CI 1.58 to 2.86) and men from the Pakistani group (1.24, 95% CI 1.06 to 1.46). Conclusion Public health strategies to increase vaccination uptake in ethnic minority groups could reduce disparities in COVID-19 mortality that cannot be accounted for by pre-existing risk factors. What is already known on this topic Ethnic minority groups in England have been disproportionately affected by the COVID-19 pandemic during the first and second waves. COVID-19 vaccination uptake is also lower among many ethnic minority groups, particularly Bangladeshi, Black African, Black Caribbean, and Pakistani groups. There is a paucity of research into whether ethnic disparities in COVID-19 mortality have continued into the third wave and the extent to which differences in vaccination uptake contribute to differences in COVID-19 mortality. What this study adds Using linked data on 28.8 million adults in England, we find that rates of COVID-19 mortality have remained higher than the White British group for most ethnic minority groups during the vaccine roll-out, notably for the Bangladeshi, Black African, Black Caribbean, and Pakistani groups. After adjustment for geographical factors, sociodemographic characteristics, pre-pandemic health status, and vaccination status, the only groups with elevated rates of COVID-19 mortality during the third wave were the Bangladeshi group and men from the Pakistani group, suggesting that increasing vaccination uptake in ethnic minority groups could reduce ethnic disparities in COVID-19 mortality.

Changes in the trajectory of Long Covid symptoms following COVID-19 vaccination: community-based cohort study (preprint)

ObjectiveTo estimate associations between COVID-19 vaccination and Long Covid symptoms in adults who were infected with SARS-CoV-2 prior to vaccination. DesignObservational cohort study using individual-level interrupted time series analysis. SettingRandom sample from the community population of the UK. Participants28,356 COVID-19 Infection Survey participants (mean age 46 years, 56% female, 89% white) aged 18 to 69 years who received at least their first vaccination after test-confirmed infection. Main outcome measuresPresence of long Covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021. ResultsMedian follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (84% of participants). First vaccination was associated with an initial 12.8% decrease (95% confidence interval: -18.6% to -6.6%) in the odds of Long Covid, but increasing by 0.3% (-0.6% to +1.2%) per week after the first dose. Second vaccination was associated with an 8.8% decrease (-14.1% to -3.1%) in the odds of Long Covid, with the odds subsequently decreasing by 0.8% (-1.2% to -0.4%) per week. There was no statistical evidence of heterogeneity in associations between vaccination and Long Covid by socio-demographic characteristics, health status, whether hospitalised with acute COVID-19, vaccine type (adenovirus vector or mRNA), or duration from infection to vaccination. ConclusionsThe likelihood of Long Covid symptoms reduced after COVID-19 vaccination, and the improvement was sustained over the follow-up period after the second dose. Vaccination may contribute to a reduction in the population health burden of Long Covid, though longer follow-up time is needed. Summary boxWhat is already known on this topic O_LICOVID-19 vaccines are effective at reducing rates of SARS-CoV-2 infection, transmission, hospitalisation, and death C_LIO_LIThe incidence of Long Covid may be reduced if infected after vaccination, but the relationship between vaccination and pre-existing long COVID symptoms is unclear, as published studies are generally small and with self-selected participants C_LI What this study adds O_LIThe likelihood of Long Covid symptoms reduced after COVID-19 vaccination, and the improvement was sustained over the follow-up period after the second dose C_LIO_LIThere was no evidence of differences in this relationship by socio-demographic characteristics, health-related factors, vaccine type, or duration from infection to vaccination C_LIO_LIAlthough causality cannot be inferred from this observational evidence, vaccination may contribute to a reduction in the population health burden of Long Covid; further research is needed to understand the biological mechanisms that may ultimately contribute to the development of therapeutics for Long Covid C_LI

Estimating the effectiveness of first dose of COVID-19 vaccine against mortality in England: a quasi-experimental study (preprint)

BackgroundEstimating real-world vaccine effectiveness is vital to assess the impact of the vaccination programme on the pandemic and inform the ongoing policy response. However, estimating vaccine effectiveness using observational data is inherently challenging because of the non-randomised design and the potential for unmeasured confounding. MethodsWe used a Regression Discontinuity Design (RDD) to estimate vaccine effectiveness against COVID-19 mortality in England, exploiting the discontinuity in vaccination rates resulting from the UKs age-based vaccination priority groups. We used the fact that people aged 80 or over were prioritised for the vaccine roll-out in the UK to compare the risk of COVID-19 and non-COVID-19 death in people aged 75-79 and 80-84. FindingsThe prioritisation of vaccination of people aged 80 or above led to a large discrepancy in vaccination rates in people 80-84 compared to those 75-79 at the beginning of the vaccination campaign. We found a corresponding difference in COVID-19 mortality, but not in non-COVID-19 mortality, suggesting that our approach appropriately addresses the issue of unmeasured confounding factors. Our results suggest that the first vaccine dose reduced the risk of COVID-19 death by 52.6% (95% Cl 26.6-84.2) in those aged 80. InterpretationsOur results support existing evidence that a first dose of a COVID-19 vaccine has a strong protective effect against COVID-19 mortality in older adults. The RDD estimate of vaccine effectiveness is comparable to previously published studies using different methods, suggesting that unmeasured confounding factors are unlikely to substantially bias these studies. FundingOffice for National Statistics. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for studies reporting on the real-world effectiveness of the COVID-19 vaccination on risk of death using terms such as "COVID-19", "vaccine effectiveness", "mortality" and "death". The relevant published studies on this topic report vaccine effectiveness estimates against risk of death ranging from 64.2% to 98.7%, for varying times post-vaccination. All of these are observational studies and therefore potentially subject to bias from unmeasured confounding. We found no studies that used a quasi-experimental method such as regression discontinuity design, which is not subject to bias from unmeasured confounding, to calculate the effectiveness of the COVID-19 vaccination on risk of COVID-19 death, or on other outcomes such as hospitalisation or infection. Added value of this studyThe estimates of vaccine effectiveness based on observational data may be biased by unmeasured confounding. This study uses a regression discontinuity design to estimate vaccine effectiveness, exploiting the fact that the vaccination campaign in the UK was rolled out following age-based priority groups. This enables the calculation of an unbiased estimate of the effectiveness of the COVID-19 vaccine against risk of death. The vaccine effectiveness estimate of 52.6% (95% Cl 26.6-84.2) is slightly lower but similar to previously published estimates, therefore suggesting that these estimates are not substantially affected by unmeasured confounding factors and confirming the effectiveness of the COVID-19 vaccine against risk of COVID-19 death. Implications of all the available evidenceObtaining an unbiased estimate of COVID-19 vaccine effectiveness is of vital importance in informing policy for lifting COVID-19 related measures. The regression discontinuity design provides confidence that the existing estimates from observational studies are unlikely to be substantially biased by unmeasured confounding.

Deaths involving COVID-19 by disability status: a retrospective analysis of 29 million adults during the first two waves of the Coronavirus pandemic in England (preprint)

Objectives To assess the association between self-reported disability and deaths involving COVID-19 among adults in England. Design Cohort study of >29 million adults using data from the Office for National Statistics Public Health Data Asset. Setting People living in private households or communal establishments (including care homes) in England. Participants 29,293,845 adults (47% male) aged 30-100 years (mean age = 56) present at the 2011 Census who were alive on 24 January 2020. The main exposure was self-reported disability from the 2011 Census. Main outcome measures Death involving COVID-19, occurring between 24 January 2020 and 28 February 2021. We estimated the age-standardised mortality rate per 100,000 person-years at-risk, stratified by sex, disability status, and wave of the pandemic. We calculated hazard ratios (HRs) for disabled people compared with non-disabled people, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions. Results Disabled people made up 17% of the study population, including 7% who were ‘more-disabled’ and 10% ‘less-disabled’. From 24 January 2020 to 28 February 2021, 105,213 people died from causes involving COVID-19 in England, 58% of whom were disabled. Age-adjusted analyses showed that, compared to non-disabled people, mortality involving COVID-19 was higher among both more-disabled people (HR=3.05, 95% CI: 2.98 to 3.11 in males; 3.48, 3.41 to 3.56 in females) and less-disabled people (HR=1.88, 95% CI: 1.84 to 1.92 in males; 2.03, 1.98 to 2.08 in females). Among people aged 30-69, HRs reached 8.47 (8.01 to 8.95) among more-disabled females and 5.42 (5.18 to 5.68) for more-disabled males. Sequential adjustment for residence type, geography, socio-demographics, and health conditions partly explained the associations, indicating that a combination of these factors contributed towards the increased risk. Conclusion Disabled people in England had markedly increased risk of mortality involving COVID-19 compared to non-disabled people and should be prioritised within the pandemic response.

Sociodemographic inequality in COVID-19 vaccination coverage amongst elderly adults in England: a national linked data study (preprint)

Objective: To examine inequalities in COVID-19 vaccination rates amongst elderly adults in England Design: Cohort study Setting: People living in private households and communal establishments in England Participants: 6,829,643 adults aged 70 years or above (mean 78.7 years, 55.2% female) who were alive on 15 March 2021. Main outcome measures: Having received the first dose of a vaccine against COVID-19 by 15 March 2021. We calculated vaccination rates and estimated unadjusted and adjusted odds ratios using logistic regression models. Results: By 15 March 2021, 93.2% of people living in England aged 70 years and over had received at least one dose of a COVID-19 vaccine. While vaccination rates differed across all factors considered apart from sex, the greatest disparities were seen between ethnic and religious groups. The lowest rates were in people of Black African and Black Caribbean ethnic backgrounds, where only 67.2% and 73.9% had received a vaccine, with adjusted odds of not being vaccinated at 5.01 (95% CI 4.86 - 5.16) and 4.85 (4.75 - 4.96) times greater than the White British group. The proportion of individuals self-identifying as Muslim and Buddhist who had received a vaccine was 79.1% and 84.1%, respectively. Older age, greater area deprivation, less advantaged socio-economic position (proxied by living in a rented home), being disabled and living either alone or in a multi-generational household were also associated with higher odds of not having received the vaccine. Conclusion: People disproportionately affected seem most hesitant to COVID-19 vaccinations. Policy Interventions to improve these disparities are urgently needed.

Occupation and COVID-19 mortality in England: a national linked data study of 14.3 million adults (preprint)

ObjectiveTo estimate occupational differences in COVID-19 mortality, and test whether these are confounded by factors, such as regional differences, ethnicity and education or due to non-workplace factors, such as deprivation or pre-pandemic health. DesignRetrospective cohort study SettingPeople living in private households England Participants14,295,900 people aged 40-64 years (mean age 52 years, 51% female) who were alive on 24 January 2020, living in private households in England in 2019, were employed in 2011, and completed the 2011 census. Main outcome measuresCOVID-19 related death, assessed between 24 January 2020 and 28 December 2020. We estimated age-standardised mortality rates per 100,000 person-years at risk (ASMR) stratified by sex and occupations. To estimate the effect of occupation due to work-related exposures, we used Cox proportional hazard models to adjust for confounding (region, ethnicity, education), as well as non-workplace factors that are related to occupation. ResultsThere is wide variation between occupations in COVID-19 mortality. Several occupations, particularly those involving contact with patients or the public, show three-fold or four-fold risks. These elevated risks were greatly attenuated after adjustment for confounding and mediating non-workplace factors. For example, the hazard ratio (HR) for men working as taxi and cab drivers or chauffeurs changed from 4.60 [95%CI 3.62-5.84] to 1.47 [1.14-1.89] after adjustment. More generally, the overall HR for men working in essential occupations compared with men in non-essential occupations changed from 1.45 [1.34 - 1.56] to 1.22 [1.13 - 1.32] after adjustment. For most occupations, confounding and other mediating factors explained about 70% to 80% of the age-adjusted hazard ratios. ConclusionsWorking conditions are likely to play a role in COVID-19 mortality, particularly in occupations involving contact with COVID-19 patients or the public. However, there is also a substantial contribution from non-workplace factors, including regional factors, socio-demographic factors, and pre-pandemic health.

Epidemiology of post-COVID syndrome following hospitalisation with coronavirus: a retrospective cohort study (preprint)

Objectives The epidemiology of post-COVID syndrome (PCS) is currently undefined. We quantified rates of organ-specific impairment following recovery from COVID-19 hospitalisation compared with those in a matched control group, and how the rate ratio (RR) varies by age, sex, and ethnicity. Design Observational, retrospective, matched cohort study. Setting NHS hospitals in England. Participants 47,780 individuals (mean age 65 years, 55% male) in hospital with COVID-19 and discharged alive by 31 August 2020, matched to controls on demographic and clinical characteristics. Outcome measures Rates of hospital readmission, all-cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney and liver diseases until 30 September 2020. Results Mean follow-up time was 140 days for COVID-19 cases and 153 days for controls. 766 (95% confidence interval: 753 to 779) readmissions and 320 (312 to 328) deaths per 1,000 person-years were observed in COVID-19 cases, 3.5 (3.4 to 3.6) and 7.7 (7.2 to 8.3) times greater, respectively, than in controls. Rates of respiratory, diabetes and cardiovascular events were also significantly elevated in COVID-19 cases, at 770 (758 to 783), 127 (122 to 132) and 126 (121 to 131) events per 1,000 person-years, respectively. RRs were greater for individuals aged <70 than ≥ 70 years, and in ethnic minority groups than the White population, with the biggest differences observed for respiratory disease: 10.5 [9.7 to 11.4] for <70 years versus 4.6 [4.3 to 4.8] for ≥ 70 years, and 11.4 (9.8 to 13.3) for Non-White versus 5.2 (5.0 to 5.5) for White. Conclusions Individuals discharged from hospital following COVID-19 face elevated rates of multi-organ dysfunction compared with background levels, and the increase in risk is neither confined to the elderly nor uniform across ethnicities. The diagnosis, treatment and prevention of PCS require integrated rather than organ- or disease-specific approaches. Urgent research is required to establish risk factors for PCS.

Ethnicity, Household Composition and COVID-19 Mortality: A National Linked Data Study (preprint)

BackgroundEthnic minorities have experienced disproportionate COVID-19 mortality rates. We estimated associations between household composition and COVID-19 mortality in older adults ([≥] 65 years) using a newly linked census-based dataset, and investigated whether living in a multi-generational household explained some of the elevated COVID-19 mortality amongst ethnic minority groups. MethodsUsing retrospective data from the 2011 Census linked to Hospital Episode Statistics (2017-2019) and death registration data (up to 27th July 2020), we followed adults aged 65 years or over living in private households in England from 2 March 2020 until 27 July 2020 (n=10,078,568). We estimated hazard ratios (HRs) for COVID-19 death for people living in a multi-generational household compared with people living with another older adult, adjusting for geographical factors, socio-economic characteristics and pre-pandemic health. We conducted a causal mediation analysis to estimate the proportion of ethnic inequalities explained by living in a multi-generational household. ResultsLiving in a multi-generational household was associated with an increased risk of COVID-19 death. After adjusting for confounding factors, the HRs for living in a multi-generational household with dependent children were 1.13 [95% confidence interval 1.01-1.27] and 1.17 [1.01-1.35] for older males and females. The HRs for living in a multi-generational household without dependent children were 1.03 [0.97 - 1.09] for older males and 1.22 [1.12 - 1.32] for older females. Living in a multi-generational household explained between 10% and 15% of the elevated risk of COVID-19 death among older females from South Asian background, but very little for South Asian males or people in other ethnic minority groups. ConclusionOlder adults living with younger people are at increased risk of COVID-19 mortality, and this is a notable contributing factor to the excess risk experienced by older South Asian females compared to White females. Relevant public health interventions should be directed at communities where such multi-generational households are highly prevalent. FundingThis research was funded by the Office for National Statistics.

Religious affiliation and the risk of COVID 19 related mortality; a retrospective analysis of variation in pre and post lockdown risk by religious group in England and Wales. (preprint)

Background COVID 19 mortality risk is associated with demographic and behavioural factors; furthermore religious gatherings have been linked with the spread of COVID. We sought to understand the variation in the risk of COVID 19 related death across religious groups in the UK both before and after lockdown. Methods We conducted a retrospective cohort study of usual residents in England and Wales enumerated at the 2011 Census (n = 48,422,583), for risk of death involving COVID-19 using linked death certificates. Cox regression models were estimated to compare risks between religious groups. Time dependent religion coefficients were added to the model allowing hazard ratios (HRs) pre and post lockdown period to be estimated separately. Results Compared to Christians all religious groups had an elevated risk of death involving COVID-19; the largest age adjusted HRs were for Muslim and Jewish males at 2.5 (95% confidence interval 2.3-2.7) and 2.1 (1.9-2.5), respectively. The corresponding HRs for Muslim and Jewish females were 1.9 (1.7-2.1) and 1.5 (1.7-2.1). The difference in risk between groups contracted after lockdown. Those who affiliated with no religion had the lowest risk of COVID 19 related death before and after lockdown. Conclusion The majority of the variation in COVID 19 mortality risk was explained by controlling for socio demographic and geographic determinants; however, Jews remained at a higher risk of death compared to all other groups. Lockdown measures were associated with reduced differences in COVID 19 mortality rates between religious groups, further research is required to understand the causal mechanisms.

Ethnic minority groups in England and Wales - factors affecting the size and timing of elevated COVID-19 mortality: a retrospective cohort study linking Census and death records (preprint)

Objectives: To estimate population-level associations between ethnicity and coronavirus disease 2019 (COVID-19) mortality, and to investigate how ethnicity-specific mortality risk evolved over the course of the pandemic. Design: Retrospective cohort study using linked administrative data. Setting: England and Wales, deaths occurring 2 March to 15 May 2020. Participants: Respondents to the 2011 Census of England and Wales aged [≤]100 years and enumerated in private households, linked to death registrations and adjusted to account for emigration before the outcome period, who were alive on 1 March 2020 (n=47,872,412). Main outcome measure: Death related to COVID-19, registered by 29 May 2020. Statistical methods: We estimated hazard ratios (HRs) for ethnic minority groups compared with the White population using Cox regression models, controlling for geographical, demographic, socio-economic, occupational, and self-reported health factors. HRs were estimated on the full outcome period and separately for pre- and post-lockdown periods in the UK. Results: In the age-adjusted models, people from all ethnic minority groups were at elevated risk of COVID-19 mortality; the HRs for Black males and females were 3.13 [95% confidence interval: 2.93 to 3.34] and 2.40 [2.20 to 2.61] respectively. However, in the fully adjusted model for females, the HRs were close to unity for all ethnic groups except Black (1.29 [1.18 to 1.42]). For males, COVID-19 mortality risk remained elevated for the Black (1.76 [1.63 to 1.90]), Bangladeshi/Pakistani (1.35 [1.21 to 1.49]) and Indian (1.30 [1.19 to 1.43]) groups. The HRs decreased after lockdown for all ethnic groups, particularly Black and Bangladeshi/Pakistani females. Conclusions: Differences in COVID-19 mortality between ethnic groups were largely attenuated by geographical and socio-economic factors, although some residual differences remained. Lockdown was associated with reductions in excess mortality risk in ethnic minority populations, which has major implications for a second wave of infection or local spikes. Further research is needed to understand the causal mechanisms underpinning observed differences in COVID-19 mortality between ethnic groups.