Abstract
The impact of long COVID is increasingly recognised, but risk factors are poorly characterised. We analysed questionnaire data on symptom duration from 10 longitudinal study (LS) samples and electronic healthcare records (EHR) to investigate sociodemographic and health risk factors associated with long COVID, as part of the UK National Core Study for Longitudinal Health and Wellbeing. Methods Analysis was conducted on 6,899 adults self-reporting COVID-19 from 45,096 participants of the UK LS, and on 3,327 cases assigned a long COVID code in primary care EHR out of 1,199,812 adults diagnosed with acute COVID-19. In LS, we derived two outcomes: symptoms lasting 4+ weeks and symptoms lasting 12+ weeks. Associations of potential risk factors (age, sex, ethnicity, socioeconomic factors, smoking, general and mental health, overweight/obesity, diabetes, hypertension, hypercholesterolaemia, and asthma) with these two outcomes were assessed, using logistic regression, with meta-analyses of findings presented alongside equivalent results from EHR analyses. Results Functionally limiting long COVID for 12+ weeks affected between 1.2% (age 20), and 4.8% (age 63) of people reporting COVID-19 in LS. The proportion reporting symptoms overall for 12+ weeks ranged from 7.8 (mean age 28) to 17% (mean age 58) and for 4+ weeks 4.2% (age 20) to 33.1% (age 56). Age was associated with a linear increase in long COVID between age 20-70. Being female (LS: OR=1.49; 95%CI:1.24-1.79; EHR: OR=1.51 [1.41-1.61]), poor pre-pandemic mental health (LS: OR=1.46 [1.17-1.83]; EHR: OR=1.57 [1.47-1.68]) and poor general health (LS: OR=1.62 [1.25-2.09]; EHR: OR=1.26; [1.18-1.35]) were associated with higher risk of long COVID. Individuals with asthma also had higher risk (LS: OR=1.32 [1.07-1.62]; EHR: OR=1.56 [1.46-1.67]), as did those categorised as overweight or obese (LS: OR=1.25 [1.01-1.55]; EHR: OR=1.31 [1.21-1.42]) though associations for symptoms lasting 12+ weeks were less pronounced. Non-white ethnic minority groups had lower 4+ week symptom risk (LS: OR=0.32 [0.22-0.47]), a finding consistent in EHR. Associations were not observed for other risk factors. Few participants in the studies had been admitted to hospital (0.8-5.2%). Conclusions Long COVID is clearly distributed differentially according to several sociodemographic and pre-existing health factors. Establishing which of these risk factors are causal and predisposing is necessary to further inform strategies for preventing and treating long COVID.
Competing Interest Statement
SVK is a member of the Scientific Advisory Group on Emergencies subgroup on ethnicity and COVID-19 and is co-chair of the Scottish Government Ethnicity Reference Group on COVID-19. NC serves on a data safety monitoring board for trials sponsored by Astra-Zeneca. CJS is an academic lead on KCL Zoe Global Ltd. COVID symptoms study.
Funding Statement
Funding acknowledgements: This work was supported by the National Core Studies, an initiative funded by UKRI, NIHR and the Health and Safety Executive. The COVID-19 Longitudinal Health and Wellbeing National Core Study was funded by the Medical Research Council (MC_PC_20030). The contributing studies have been made possible because of the tireless dedication, commitment and enthusiasm of the many people who have taken part. We would like to thank the participants and the numerous team members involved in the studies including interviewers, technicians, researchers, administrators, managers, health professionals and volunteers. We are additionally grateful to our funders for their financial input and support in making this research happen. Studies acknowledgements: Data gathered from questionnaire(s) was provided by Wellcome Longitudinal Population Study (LPS) COVID-19 Steering Group and Secretariat (221574/Z/20/Z). Understanding Society is an initiative funded by the Economic and Social Research Council and various Government Departments, with scientific leadership by the Institute for Social and Economic Research, University of Essex, and survey delivery by NatCen Social Research and Kantar Public. The Understanding Society COVID-19 study is funded by the Economic and Social Research Council (ES/K005146/1) and the Health Foundation (2076161). The research data are distributed by the UK Data Service. The Millennium Cohort Study, Next Steps, British Cohort Study 1970 and National Child Development Study 1958 are supported by the Centre for Longitudinal Studies, Resource Centre 2015-20 grant (ES/M001660/1) and a host of other co-funders. The COVID-19 data collections in these five cohorts were funded by the UKRI grant Understanding the economic, social and health impacts of COVID-19 using lifetime data: evidence from 5 nationally representative UK cohorts (ES/V012789/1). The UK Medical Research Council and Wellcome (Grant Ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. Please note that the study website contains details of all the data that is available through a fully searchable data dictionary and variable search tool and reference the following webpage: http://www.bristol.ac.uk/alspac/researchers/our-data/. Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Part of this data was collected using REDCap, see the REDCap website for details https://projectredcap.org/resources/citations/ TwinsUK receives funding from the Wellcome Trust (WT212904/Z/18/Z), the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust and Kings College London.The TwinsUK COVID-19 personal experience study was funded by the Kings Together Rapid COVID-19 Call award, under the projects original title Keeping together through coronavirus: The physical and mental health implications of self-isolation due to the Covid-19 TwinsUK is also supported by the Chronic Disease Research Foundation and Zoe Global Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award STratifying Resilience and Depression Longitudinally (STRADL) Reference 104036/Z/14/Z). Generation Scotland is funded by the Wellcome Trust (216767/Z/19/Z). Born in Bradford (BiB) receives core infrastructure funding from the Wellcome Trust (WT101597MA), and a joint grant from the UK Medical Research Council (MRC) and UK Economic and Social Science Research Council (ESRC) (MR/N024397/1) and one from the British Heart Foundation (BHF) (CS/16/4/32482). The National Institute for Health Research Yorkshire and Humber ARC, and Clinical Research Network both provide support for BiB research. Born in Bradford is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, health professionals, schools and researchers who have made Born in Bradford happen. OpenSAFELY is jointly funded by UKRI, NIHR and Asthma UK-BLF [COV0076; MR/V015737/] and the Longitudinal Health and Wellbeing strand of the National Core Studies programme. EMIS and TPP provided technical expertise and infrastructure within their data environments pro bono in the context of a national emergency. The OpenSAFELY software platform is supported by a Wellcome Discretionary Award. BGs work on clinical informatics is supported by the NIHR Oxford Biomedical Research Centre and the NIHR Applied Research Collaboration Oxford and Thames Valley. Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, Public Health England or the Department of Health and Social Care. People funding: NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre, the MRC Integrative Epidemiology Unit (MC_UU_00011/1) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A29019). SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). ASFK acknowledges funding from the ESRC (ES/V011650/1). EJT acknowledges funding from the Wellcome Trust (WT212904/Z/18/Z). RM acknowledges support from the Elizabeth Blackwell Institute for Health Research, University of Bristol, and the Wellcome Trust Institutional Strategic Support Fund (204813/Z/16/Z). GBP acknowledges funding from the Economic and Social Research Council (ES/V012789/1). CLN acknowledges funding from the Medical Research Council (MR/R024774/1). KT works in a Unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_00011/3). DMW is supported by funding from UK Medical Research Council (MC_PC_20030). NC is supported by funding from the UK Medical Research Council (MC_UU_00019/2)
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