Socioeconomic inequalities of Long COVID: a retrospective population-based cohort study in the United Kingdom.

OBJECTIVES: To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the inequality by sex and occupation. DESIGN: We conducted a retrospective population-based cohort study using data from the ONS COVID-19 Infection Survey between 26 April 2020 and 31 January 2022. This is the largest nationally representative survey of COVID-19 in the UK with longitudinal data on occupation, COVID-19 exposure and Long COVID. SETTING: Community-based survey in the UK. PARTICIPANTS: A total of 201,799 participants aged 16 to 64 years and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MAIN OUTCOME MEASURES: The risk of Long COVID at least 4 weeks after SARS-CoV-2 infection by index of multiple deprivation (IMD) and the modifying effects of socioeconomic deprivation by sex and occupation. RESULTS: Nearly 10% (n = 19,315) of participants reported having Long COVID. Multivariable logistic regression models, adjusted for a range of variables (demographic, co-morbidity and time), showed that participants in the most deprived decile had a higher risk of Long COVID (11.4% vs. 8.2%; adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.34, 1.59) compared to the least deprived decile. Significantly higher inequalities (most vs. least deprived decile) in Long COVID existed in healthcare and patient-facing roles (aOR: 1.76; 95% CI: 1.27, 2.44), in the education sector (aOR: 1.68; 95% CI: 1.31, 2.16) and in women (aOR: 1.56; 95% CI: 1.40, 1.73) than men (aOR: 1.32; 95% CI: 1.15, 1.51). CONCLUSIONS: This study provides insights into the heterogeneous degree of inequality in Long COVID by deprivation, sex and occupation. These findings will help inform public health policies and interventions in incorporating a social justice and health inequality lens.

Mortality in COVID-19 among women on hormone replacement therapy: a retrospective cohort study.

BACKGROUND: Limited recent observational data have suggested that there may be a protective effect of oestrogen on the severity of COVID-19 disease. Our aim was to investigate the association between hormone replacement therapy (HRT) or combined oral contraceptive pill (COCP) use and the likelihood of death in women with COVID-19. METHODS: We undertook a retrospective cohort study using routinely collected computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. We identified a cohort of 1,863,478 women over 18 years of age from 465 general practices in England. Mixed-effects logistic regression models were used to quantify the association between HRT or COCP use and all-cause mortality among women diagnosed with confirmed or suspected COVID-19 in unadjusted and adjusted models. RESULTS: There were 5,451 COVID-19 cases within the cohort. HRT was associated with a reduction in all-cause mortality in COVID-19 (adjusted OR 0.22, 95% CI 0.05 to 0.94). There were no reported events for all-cause mortality in women prescribed COCPs. This prevented further examination of the impact of COCP. CONCLUSIONS: We found that HRT prescription within 6 months of a recorded diagnosis of COVID-19 infection was associated with a reduction in all-cause mortality. Further work is needed in larger cohorts to examine the association of COCP in COVID-19, and to further investigate the hypothesis that oestrogens may contribute a protective effect against COVID-19 severity.

Ethnic disparities in COVID-19 outcomes: a multinational cohort study of 20 million individuals from England and Canada.

BACKGROUND: Heterogeneous studies have demonstrated ethnic inequalities in the risk of SARS-CoV-2 infection and adverse COVID-19 outcomes. This study evaluates the association between ethnicity and COVID-19 outcomes in two large population-based cohorts from England and Canada and investigates potential explanatory factors for ethnic patterning of severe outcomes. METHODS: We identified adults aged 18 to 99 years in the QResearch primary care (England) and Ontario (Canada) healthcare administrative population-based datasets (start of follow-up: 24th and 25th Jan 2020 in England and Canada, respectively; end of follow-up: 31st Oct and 30th Sept 2020, respectively). We harmonised the definitions and the design of two cohorts to investigate associations between ethnicity and COVID-19-related death, hospitalisation, and intensive care (ICU) admission, adjusted for confounders, and combined the estimates obtained from survival analyses. We calculated the 'percentage of excess risk mediated' by these risk factors in the QResearch cohort. RESULTS: There were 9.83 million adults in the QResearch cohort (11,597 deaths; 21,917 hospitalisations; 2932 ICU admissions) and 10.27 million adults in the Ontario cohort (951 deaths; 5132 hospitalisations; 1191 ICU admissions). Compared to the general population, pooled random-effects estimates showed that South Asian ethnicity was associated with an increased risk of COVID-19 death (hazard ratio: 1.63, 95% CI: 1.09-2.44), hospitalisation (1.53; 1.32-1.76), and ICU admission (1.67; 1.23-2.28). Associations with ethnic groups were consistent across levels of deprivation. In QResearch, sociodemographic, lifestyle, and clinical factors accounted for 42.9% (South Asian) and 39.4% (Black) of the excess risk of COVID-19 death. CONCLUSION: International population-level analyses demonstrate clear ethnic inequalities in COVID-19 risks. Policymakers should be cognisant of the increased risks in some ethnic populations and design equitable health policy as the pandemic continues.

Mortality from angiotensin-converting enzyme-inhibitors and angiotensin receptor blockers in people infected with COVID-19: a cohort study of 3.7 million people.

BACKGROUND: Concerns have been raised that angiotensin-converting enzyme-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) might facilitate transmission of severe acute respiratory syndrome coronavirus 2 leading to more severe coronavirus disease (COVID-19) disease and an increased risk of mortality. We aimed to investigate the association between ACE-I/ARB treatment and risk of death amongst people with COVID-19 in the first 6 months of the pandemic. METHODS: We identified a cohort of adults diagnosed with either confirmed or probable COVID-19 (from 1 January to 21 June 2020) using computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. This comprised 465 general practices in England, United Kingdom with a nationally representative population of 3.7 million people. We constructed mixed-effects logistic regression models to quantify the association between ACE-I/ARBs and all-cause mortality among people with COVID-19, adjusted for sociodemographic factors, comorbidities, concurrent medication, smoking status, practice clustering, and household number. RESULTS: There were 9,586 COVID-19 cases in the sample and 1,463 (15.3%) died during the study period between 1 January 2020 and 21 June 2020. In adjusted analysis ACE-I and ARBs were not associated with all-cause mortality (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 0.85-1.21 and OR 0.84, 95% CI 0.67-1.07, respectively). CONCLUSION: Use of ACE-I/ARB, which are commonly used drugs, did not alter the odds of all-cause mortality amongst people diagnosed with COVID-19. Our findings should inform patient and prescriber decisions concerning continued use of these medications during the pandemic.

Postal methods for monitoring HbA1c in diabetes mellitus: A protocol for systematic review.

BACKGROUND: Worldwide there are an estimated 463 million people with diabetes. In the UK people with diabetes are offered annual review which includes monitoring of Haemoglobin A1c (HbA1c). This can identify people with diabetes who are not meeting their glycaemic targets, enabling early intervention. Those who do not attend these reviews often have poorer health outcomes. During the Coronavirus disease 2019 (COVID-19) pandemic, there was a 77% reduction in monitoring of HbA1c in the UK. AIM: We hypothesise that people with diabetes could take finger-prick samples at home for measurement of HbA1c. We will examine the agreement and correlation of capillary HbA1c values compared to a venous reference standard. We will explore reliability and repeatability of capillary HbA1c testing methods. We will explore the direction of effect of storage variables. We will also explore patient acceptability and safety. We will look at capillary blood methods which would be suitable for posting. METHOD: Using core terms of 'Diabetes', 'HbA1c' and 'Capillary sampling' we will search MEDLINE, Embase, CINAHL, Web of Science Core Collection, Google Scholar, Open Grey, and other grey literature from database inception until 2021. Risk of bias will be assessed using the 'COSMIN risk of bias tool to assess the quality of studies on reliability and measurement error'. CONCLUSION: We will produce a narrative synthesis to explore whether there are viable postal alternatives to venous sampling as well as exploring acceptability and safety of patient self-collection. PROSPERO REGISTRATION NUMBER: CRD42021225606.

Change in treatment burden among people with multimorbidity: Protocol of a follow up survey and development of efficient measurement tools for primary care.

BACKGROUND: Treatment burden is the effort required of patients to look after their health and the impact this has on their functioning and wellbeing. It is likely treatment burden changes over time as circumstances change for patients and health services. However, there are a lack of population-level studies of treatment burden change and factors associated with this change over time. Furthermore, there are currently no practical screening tools for treatment burden in time-pressured clinical settings or at population level. METHODS AND ANALYSIS: This is a three-year follow-up of a cross-sectional survey of 723 people with multimorbidity (defined as three or more long-term conditions; LTCs) registered at GP practices in in Dorset, England. The survey will repeat collection of information on treatment burden (using the 10-item Multimorbidity Treatment Burden Questionnaire (MTBQ) and a novel single-item screening tool), sociodemographics, medications, LTCs, health literacy and financial resource, as at baseline. Descriptive statistics will be used to compare change in treatment burden since the baseline survey in 2019 and associations of treatment burden change will be assessed using regression methods. Diagnostic test accuracy metrics will be used to evaluate the single-item treatment burden screening tool using the MTBQ as the gold-standard. Routine primary care data (including demographics, medications, LTCs, and healthcare usage data) will be extracted from medical records for consenting participants. A forward-stepwise, likelihood-ratio logistic regression model building approach will be employed in order to assess the utility of routine data metrics in quantifying treatment burden in comparison to self-reported treatment burden using the MTBQ. IMPACT: To the authors' knowledge, this will be the first study investigating longitudinal aspects of treatment burden. Findings will improve understanding of the extent to which treatment burden changes over time for people with multimorbidity and factors contributing to this change, as well as allowing better identification of people at risk of high treatment burden.

Primary care consultations for respiratory tract symptoms during the COVID-19 pandemic: a cohort study including 70,000 people in South West England.

BACKGROUND: Primary care consultations for respiratory tract symptoms including identifying and managing COVID-19 during the pandemic have not been characterized. METHODS: A retrospective cohort analysis using routinely collected records from 70,431 adults aged 18+ in South England within the Electronic Care and Health Information Analytics (CHIA) database. Total volume and type of consultations (face-to-face, home visits, telephone, email/video, or out of hours) for respiratory tract symptoms between 1 January and 31 July 2020 (during the first wave of the pandemic) were compared with the equivalent period in 2019 for the same cohort. Descriptive statistics were used to summarize consultations by sociodemographic and clinical characteristics, and by COVID-19 diagnosis and outcomes (death, hospitalization, and pneumonia). RESULTS: Overall consultations for respiratory tract symptoms increased by 229% during the pandemic compared with the preceding year. This included significant increases in telephone consultations by 250%, a 1,574% increase in video/email consultations, 105% increase in home visits, and 92% increase in face-to-face consultations. Nearly 60% of people who presented with respiratory symptoms were tested for COVID-19 and 16% confirmed or clinically suspected to have the virus. Those with complications including pneumonia, requiring hospitalization, and who died were more likely to be seen in-person. CONCLUSION: During the pandemic, primary care substantially increased consultations for respiratory tract symptoms to identify and manage people with COVID-19. These findings should be balanced against national reports of reduced GP workload for non-COVID care.

Association Between Race and COVID-19 Outcomes Among 2.6 Million Children in England.

Importance: Although children mainly experience mild COVID-19 disease, hospitalization rates are increasing, with limited understanding of underlying factors. There is an established association between race and severe COVID-19 outcomes in adults in England; however, whether a similar association exists in children is unclear. Objective: To investigate the association between race and childhood COVID-19 testing and hospital outcomes. Design, Setting, Participants: In this cohort study, children (0-18 years of age) from participating family practices in England were identified in the QResearch database between January 24 and November 30, 2020. The QResearch database has individually linked patients with national SARS-CoV-2 testing, hospital admission, and mortality data. Exposures: The main characteristic of interest is self-reported race. Other exposures were age, sex, deprivation level, geographic region, household size, and comorbidities (asthma; diabetes; and cardiac, neurologic, and hematologic conditions). Main Outcomes and Measures: The primary outcome was hospital admission with confirmed COVID-19. Secondary outcomes were SARS-CoV-2-positive test result and any hospital attendance with confirmed COVID-19 and intensive care admission. Results: Of 2 576 353 children (mean [SD] age, 9.23 [5.24] years; 48.8% female), 410 726 (15.9%) were tested for SARS-CoV-2 and 26 322 (6.4%) tested positive. A total of 1853 children (0.07%) with confirmed COVID-19 attended hospital, 343 (0.01%) were admitted to the hospital, and 73 (0.002%) required intensive care. Testing varied across race. White children had the highest proportion of SARS-CoV-2 tests (223 701/1 311 041 [17.1%]), whereas Asian children (33 213/243 545 [13.6%]), Black children (7727/93 620 [8.3%]), and children of mixed or other races (18 971/147 529 [12.9%]) had lower proportions. Compared with White children, Asian children were more likely to have COVID-19 hospital admissions (adjusted odds ratio [OR], 1.62; 95% CI, 1.12-2.36), whereas Black children (adjusted OR, 1.44; 95% CI, 0.90-2.31) and children of mixed or other races (adjusted OR, 1.40; 95% CI, 0.93-2.10) had comparable hospital admissions. Asian children were more likely to be admitted to intensive care (adjusted OR, 2.11; 95% CI, 1.07-4.14), and Black children (adjusted OR, 2.31; 95% CI, 1.08-4.94) and children of mixed or other races (adjusted OR, 2.14; 95% CI, 1.25-3.65) had longer hospital admissions (≥36 hours). Conclusions and Relevance: In this large population-based study exploring the association between race and childhood COVID-19 testing and hospital outcomes, several race-specific disparities were observed in severe COVID-19 outcomes. However, ascertainment bias and residual confounding in this cohort study should be considered before drawing any further conclusions. Overall, findings of this study have important public health implications internationally.

Is rapid scientific publication also high quality? Bibliometric analysis of highly disseminated COVID-19 research papers.

The impact of COVID-19 has underlined the need for reliable information to guide clinical practice and policy. This urgency has to be balanced against disruption to journal handling capacity and the continued need to ensure scientific rigour. We examined the reporting quality of highly disseminated COVID-19 research papers using a bibliometric analysis examining reporting quality and risk of bias (RoB) amongst 250 top scoring Altmetric Attention Score (AAS) COVID-19 research papers between January and April 2020. Method-specific RoB tools were used to assess quality. After exclusions, 84 studies from 44 journals were included. Forty-three (51%) were case series/studies, and only one was an randomized controlled trial. Most authors were from institutions based in China (n = 44, 52%). The median AAS and impact factor was 2015 (interquartile range [IQR] 1,105-4,051.5) and 12.8 (IQR 5-44.2) respectively. Nine studies (11%) utilized a formal reporting framework, 62 (74%) included a funding statement, and 41 (49%) were at high RoB. This review of the most widely disseminated COVID-19 studies highlights a preponderance of low-quality case series with few research papers adhering to good standards of reporting. It emphasizes the need for cautious interpretation of research and the increasingly vital responsibility that journals have in ensuring high-quality publications.

Quantifying the association between ethnicity and COVID-19 mortality: a national cohort study protocol.

INTRODUCTION: Recent evidence suggests that ethnic minority groups are disproportionately at increased risk of hospitalisation and death from SARS-CoV-2 infection. Population-based evidence on potential explanatory factors across minority groups and within subgroups is lacking. This study aims to quantify the association between ethnicity and the risk of hospitalisation and mortality due to COVID-19. METHODS AND ANALYSIS: This is a retrospective cohort study of adults registered across a representative and anonymised national primary care database (QResearch) that includes data on 10 million people in England. Sociodemographic, deprivation, clinical and domicile characteristics will be summarised and compared across ethnic subgroups (categorised as per 2011 census). Cox models will be used to calculate HR for hospitalisation and COVID-19 mortality associated with ethnic group. Potential confounding and explanatory factors (such as demographic, socioeconomic and clinical) will be adjusted for within regression models. The percentage contribution of distinct risk factor classes to the excess risks seen in ethnic groups/subgroups will be calculated. ETHICS AND DISSEMINATION: The study has undergone ethics review in accordance with the QResearch agreement (reference OX102). Findings will be disseminated through peer-reviewed manuscripts, presentations at scientific meetings and conferences with national and international stakeholders.

The Use of Primary Care Big Data in Understanding the Pharmacoepidemiology of COVID-19: A Consensus Statement From the COVID-19 Primary Care Database Consortium.

The use of big data containing millions of primary care medical records provides an opportunity for rapid research to help inform patient care and policy decisions during the first and subsequent waves of the coronavirus disease 2019 (COVID-19) pandemic. Routinely collected primary care data have previously been used for national pandemic surveillance, quantifying associations between exposures and outcomes, identifying high risk populations, and examining the effects of interventions at scale, but there is no consensus on how to effectively conduct or report these data for COVID-19 research. A COVID-19 primary care database consortium was established in April 2020 and its researchers have ongoing COVID-19 projects in overlapping data sets with over 40 million primary care records in the United Kingdom that are variously linked to public health, secondary care, and vital status records. This consensus agreement is aimed at facilitating transparency and rigor in methodological approaches, and consistency in defining and reporting cases, exposures, confounders, stratification variables, and outcomes in relation to the pharmacoepidemiology of COVID-19. This will facilitate comparison, validation, and meta-analyses of research during and after the pandemic.

Association between influenza vaccination and hospitalisation or all-cause mortality in people with COVID-19: a retrospective cohort study.

INTRODUCTION: Recent evidence suggests that influenza vaccination may offer protection against COVID-19 severity. Our aim was to quantify the association between influenza vaccination status and risk of hospitalisation or all-cause mortality in people diagnosed with COVID-19. METHODS: A retrospective cohort study using routinely collected health records from patients registered to a General Practitioner (GP) practice in South West England within the Electronic Care and Health Information Analytics database. The cohort included 6921 people with COVID-19 during the first wave of the pandemic (1 January-31 July 2020). Data on influenza vaccination, hospitalisation and all-cause mortality were ascertained through linked clinical and demographic records. We applied propensity score methods (stabilised inverse probability of treatment weight) to quantify the association between influenza vaccination status and COVID-19 outcomes (hospitalisation or all-cause mortality). RESULTS: 2613 (38%) participants received an influenza vaccination between 1 January 2019 and COVID-19 diagnosis. Receipt of influenza vaccination was associated with a significantly lower odds of hospitalisation or all-cause mortality (adjusted OR: 0.85, 95% CI 0.75 to 0.97, p=0.02), and 24% reduced odds of all-cause mortality (adjusted OR: 0.76, 95% CI 0.64 to 0.90). DISCUSSION: Influenza vaccination was associated with a 15%-24% lower odds of severe COVID-19 outcomes. The current UK influenza vaccination programme needs urgent expansion as an integral component of the ongoing response plans to the COVID-19 pandemic.

Social inequality and the syndemic of chronic disease and COVID-19: county-level analysis in the USA.

BACKGROUND: Given the effect of chronic diseases on risk of severe COVID-19 infection, the present pandemic may have a particularly profound impact on socially disadvantaged counties. METHODS: Counties in the USA were categorised into five groups by level of social vulnerability, using the Social Vulnerability Index (a widely used measure of social disadvantage) developed by the US Centers for Disease Control and Prevention. The incidence and mortality from COVID-19, and the prevalence of major chronic conditions were calculated relative to the least vulnerable quintile using Poisson regression models. RESULTS: Among 3141 counties, there were 5 010 496 cases and 161 058 deaths from COVID-19 by 10 August 2020. Relative to the least vulnerable quintile, counties in the most vulnerable quintile had twice the rates of COVID-19 cases and deaths (rate ratios 2.11 (95% CI 1.97 to 2.26) and 2.42 (95% CI 2.22 to 2.64), respectively). Similarly, the prevalence of major chronic conditions was 24%-41% higher in the most vulnerable counties. Geographical clustering of counties with high COVID-19 mortality, high chronic disease prevalence and high social vulnerability was found, especially in southern USA. CONCLUSION: Some counties are experiencing a confluence of epidemics from COVID-19 and chronic diseases in the context of social disadvantage. Such counties are likely to require enhanced public health and social support.

Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review.

OBJECTIVE: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease. DESIGN: Systematic review. DATA SOURCE: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science. STUDY SELECTION: Any design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. DATA EXTRACTION AND SYNTHESIS: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies. RESULTS: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2). CONCLUSIONS: There is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.

Drug treatments affecting ACE2 in COVID-19 infection: a systematic review protocol.

BACKGROUND: The SARS-CoV-2 virus causing COVID-19 binds human angiotensin-converting enzyme 2 (ACE2) receptors in human tissues. ACE2 expression may be associated with COVID-19 infection and mortality rates. Routinely prescribed drugs that up- or down-regulate ACE2 expression are, therefore, of critical research interest as agents that might promote or reduce risk of COVID-19 infection in a susceptible population. AIM: To collate evidence on routinely prescribed drug treatments in the UK that could up- or down-regulate ACE2, and thus potentially affect COVID-19 infection. DESIGN & SETTING: Systematic review of studies published in MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), the Cochrane Library, and Web of Science from inception to 1 April 2020. METHOD: A systematic review will be conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Inclusion criteria will be: (1) assesses the effect of drug exposure on ACE2 level of expression or activity; (2) the drug is included in the British National Formulary (BNF) and, therefore, available to prescribe in the UK; and (3) a control, placebo, or sham group is included as comparator. Exclusion criteria will be: (1) ACE2 measurement in utero; (2) ACE2 measurement in children aged <18 years; (3) drug not in the BNF; and (4) review article. Quality will be assessed using the Cochrane risk of bias tool for human studies, and the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool for animal studies. RESULTS: Data will be reported in summary tables and narrative synthesis. CONCLUSION: This systematic review will identify drug therapies that may increase or decrease ACE2 expression. This might identify medications increasing risk of COVID-19 transmission, or as targets for intervention in mitigating transmission.