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Association of SARS-CoV-2 Infection With Psychological Distress, Psychotropic Prescribing, Fatigue, and Sleep Problems Among UK Primary Care Patients

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To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is SARS-CoV-2 infection associated with risk of subsequent psychiatric morbidity, sleep problems, or fatigue?

Findings  In this cohort study of the health care records of 11 923 105 patients, including 226 521 patients with SARS-CoV-2 infection, while infection was associated with increased risk of sleep problems and fatigue, associations with subsequent psychiatric morbidity were mixed.

Meaning  These findings suggest that psychiatric morbidity associated with SARS-CoV-2 infection may be overstated in analyses of health care records that do not sufficiently control for confounding.

Abstract

Importance  Infection with SARS-CoV-2 is associated with fatigue and sleep problems long after the acute phase of COVID-19. In addition, there are concerns of SARS-CoV-2 infection causing psychiatric illness; however, evidence of a direct effect is inconclusive.

Objective  To assess risk of risk of incident or repeat psychiatric illness, fatigue, or sleep problems following SARS-CoV-2 infection and to analyze changes according to demographic subgroups.

Design, Setting, and Participants  This cohort study assembled matched cohorts using the Clinical Practice Research Datalink Aurum, a UK primary care registry of 11 923 499 individuals aged 16 years or older. Patients were followed-up for up to 10 months, from February 1 to December 9, 2020. Individuals with less than 2 years of historical data or less than 1 week follow-up were excluded. Individuals with positive results on a SARS-CoV-2 test without prior mental illness or with anxiety or depression, psychosis, fatigue, or sleep problems were matched with up to 4 controls based on sex, general practice, and year of birth. Controls were individuals who had negative SARS-CoV-2 test results. Data were analyzed from January to July 2021.

Exposure  SARS-CoV-2 infection, determined via polymerase chain reaction testing.

Main Outcomes and Measures  Cox proportional hazard models estimated the association between a positive SARS-CoV-2 test result and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue, or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking, and body mass index.

Results  Of 11 923 105 eligible individuals (6 011 020 [50.4%] women and 5 912 085 [49.6%] men; median [IQR] age, 44 [30-61] years), 232 780 individuals (2.0%) had positive result on a SARS-CoV-2 test. After applying selection criteria, 86 922 individuals were in the matched cohort without prior mental illness, 19 020 individuals had prior anxiety or depression, 1036 individuals had psychosis, 4152 individuals had fatigue, and 4539 individuals had sleep problems. After adjusting for observed confounders, there was an association between positive SARS-CoV-2 test results and psychiatric morbidity (adjusted hazard ratio [aHR], 1.83; 95% CI, 1.66-2.02), fatigue (aHR, 5.98; 95% CI, 5.33-6.71), and sleep problems (aHR, 3.16; 95% CI, 2.64-3.78). However, there was a similar risk of incident psychiatric morbidity for those with a negative SARS-CoV-2 test results (aHR, 1.71; 95% CI, 1.65-1.77) and a larger increase associated with influenza (aHR, 2.98; 95% CI, 1.55-5.75).

Conclusions and Relevance  In this cohort study of individuals registered at an English primary care practice during the pandemic, there was consistent evidence that SARS-CoV-2 infection was associated with increased risk of fatigue and sleep problems. However, the results from the negative control analysis suggest that unobserved confounding may be responsible for at least some of the positive association between COVID-19 and psychiatric morbidity.

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Article Information

Accepted for Publication: September 22, 2021.

Published: November 16, 2021. doi:10.1001/jamanetworkopen.2021.34803

Correction: This article was corrected on March 7, 2022, to fix the title of Figure 1.

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Abel KM et al. JAMA Network Open.

Corresponding Author: Matthias Pierce, PhD, Centre for Women’s Mental Health, University of Manchester, Oxford Road, Jean McFarlane Building, Room 3.307, Manchester M13 9PL, United Kingdom (matthias.pierce@manchester.ac.uk).

Author Contributions: Drs Carr and Pierce had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Abel, Ashcroft, Chalder, Chew-Graham, Kapur, McManus, Steeg, Webb, Pierce.

Acquisition, analysis, or interpretation of data: Abel, Carr, Ashcroft, Chalder, Hope, Kapur, McManus, Steeg, Webb, Pierce.

Drafting of the manuscript: Abel, Chalder, Kapur, McManus, Pierce.

Critical revision of the manuscript for important intellectual content: Carr, Ashcroft, Chalder, Chew-Graham, Hope, Kapur, McManus, Steeg, Webb, Pierce.

Statistical analysis: Carr, Pierce.

Obtained funding: Ashcroft.

Administrative, technical, or material support: Carr, Ashcroft, Hope, McManus, Steeg.

Supervision: Kapur.

Conflict of Interest Disclosures: Prof Chalder reported receiving grants from National Institute for Health Research (NIHR) Biomedical Research Centre at South London, Maudsley National Health Service (NHS) Foundation Trust, and King’s College London during the conduct of the study and grants from Guy’s and St Thomas’ Charity; personal fees from Sheldon Press, Constable and Robinson, and NHS England for workshops; and serving as a member of the COVID-19 Rapid Guidelines committee for the National Institute for Health and Care Excellence outside the submitted work. Dr Kapur reported receiving grants and personal fees from the Department of Health and Social Care, NIHR, National Institute of Health and Care Excellence outside the submitted work. No other disclosures were reported.

Funding/Support: This work was funded by the NIHR through the Greater Manchester Patient Safety Translational Research Centre (award No. PSTRC-2016-003). Prof Chew-Graham is partly funded by the NIHR West Midlands Applied Research Collaboration. Dr Kapur is also supported by Greater Manchester Mental Health NHS Foundation Trust.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The interpretation and conclusions contained in this study are those of the authors alone, and not necessarily those of the Medicines and Healthcare products Regulatory Agency, NHS, NIHR, or the UK Department of Health and Social Care.

References
1.
Office for National Statistics. The prevalence of long COVID symptoms and COVID-19 complications. Updated December 2020. Accessed October 18, 2021. https://www.ons.gov.uk/news/statementsandletters/theprevalenceoflongcovidsymptomsandcovid19complications
2.
López-León  S , Wegman-Ostrosky  T , Perelman  C ,  et al.  More than 50 long-term effects of COVID-19: a systematic review and meta-analysis.   Sci Rep. 2021;11(1):16144. doi:10.1038/s41598-021-95565-8PubMedGoogle ScholarCrossref
3.
Taquet  M , Luciano  S , Geddes  JR , Harrison  PJ .  Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA.   Lancet Psychiatry. 2021;8(2):130-140. doi:10.1016/S2215-0366(20)30462-4PubMedGoogle ScholarCrossref
4.
Taquet  M , Geddes  JR , Husain  M , Luciano  S , Harrison  PJ .  6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.   Lancet Psychiatry. 2021;8(5):416-427. doi:10.1016/S2215-0366(21)00084-5PubMedGoogle ScholarCrossref
5.
Niedzwiedz  CL , Benzeval  M , Hainey  K , Leyland  AH , Katikireddi  SV .  Psychological distress among people with probable COVID-19 infection: analysis of the UK Household Longitudinal Study.   BJPsych Open. 2021;7(3):e104. doi:10.1192/bjo.2021.63 PubMedGoogle Scholar
6.
Daugherty  SE , Guo  Y , Heath  K ,  et al.  Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study.   BMJ. 2021;373:n1098. doi:10.1136/bmj.n1098 PubMedGoogle Scholar
7.
Al-Aly  Z , Xie  Y , Bowe  B .  High-dimensional characterization of post-acute sequelae of COVID-19.   Nature. 2021;594(7862):259-264. doi:10.1038/s41586-021-03553-9 PubMedGoogle ScholarCrossref
8.
Pierce  M , McManus  S , Hope  H ,  et al.  Mental health responses to the COVID-19 pandemic: a latent class trajectory analysis using longitudinal UK data.   Lancet Psychiatry. 2021;8(7):610-619. doi:10.1016/S2215-0366(21)00151-6 PubMedGoogle ScholarCrossref
9.
Mazza  MG , De Lorenzo  R , Conte  C ,  et al; COVID-19 BioB Outpatient Clinic Study group.  Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors.   Brain Behav Immun. 2020;89(July):594-600. doi:10.1016/j.bbi.2020.07.037 PubMedGoogle Scholar
10.
Rogers  JP , Chesney  E , Oliver  D ,  et al.  Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.   Lancet Psychiatry. 2020;7(7):611-627. doi:10.1016/S2215-0366(20)30203-0 PubMedGoogle ScholarCrossref
11.
Lund  LC , Hallas  J , Nielsen  H ,  et al.  Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study.   Lancet Infect Dis. 2021;21(10):1373-1382. doi:10.1016/S1473-3099(21)00211-5PubMedGoogle ScholarCrossref
12.
Smith  LE , Potts  HWW , Amlôt  R , Fear  NT , Michie  S , Rubin  GJ .  Adherence to the test, trace, and isolate system in the UK: results from 37 nationally representative surveys.   BMJ. 2021;372(n608):n608. doi:10.1136/bmj.n608 PubMedGoogle Scholar
13.
Centers for Disease Control and Prevention. Estimated COVID-19 burden. Updated July 2021. Accessed August 23, 2021. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burden.html
14.
Lipsitch  M , Tchetgen Tchetgen  E , Cohen  T .  Negative controls: a tool for detecting confounding and bias in observational studies.   Epidemiology. 2010;21(3):383-388. doi:10.1097/EDE.0b013e3181d61eeb PubMedGoogle ScholarCrossref
15.
CPRD. Clinical contact with health services for mental illness and self-harm before, during and after the COVID-19 pandemic. Accessed October 18, 2021. https://cprd.com/protocol/clinical-contact-health-services-mental-illness-and-self-harm-during-and-after-covid-19
16.
Center for Open Science. COVID-19 infection and risk of developing a mental illness, fatigue symptoms, sleep problems or self-harming behaviour. Accessed October 21, 2021. https://osf.io/rs9d8/
17.
Wolf  A , Dedman  D , Campbell  J ,  et al.  Data resource profile: Clinical Practice Research Datalink (CPRD) Aurum.   Int J Epidemiol. 2019;48(6):1740-1740g. doi:10.1093/ije/dyz034 PubMedGoogle ScholarCrossref
18.
Medicines & Healthcare Products Regulatory Agency. Feasibility counts for SARS-CoV-2-related codes in CPRD primary care data. Accessed October 18, 2021. https://www.cprd.com/sites/default/files/SARS-CoV-2%20counts%20June21_v1.0.pdf
19.
Coronavirus test results now visible to GPs. News release. NHS Digital. July 20, 2020. Accessed May 24, 2021. https://digital.nhs.uk/news-and-events/latest-news/coronavirus-test-results-now-visible-to-gps
20.
Steeg  S . Primary care contact for mental illness and self-harm before, during and after the peak of the COVID-19 pandemic in the UK: cohort study of 13 million individuals. Accessed October 18, 2021. https://clinicalcodes.rss.mhs.man.ac.uk/medcodes/article/173/
21.
Charlson  M , Szatrowski  TP , Peterson  J , Gold  J .  Validation of a combined comorbidity index.   J Clin Epidemiol. 1994;47(11):1245-1251. doi:10.1016/0895-4356(94)90129-5 PubMedGoogle ScholarCrossref
22.
Wessely  S , Chalder  T , Hirsch  S , Pawlikowska  T , Wallace  P , Wright  DJ .  Postinfectious fatigue: prospective cohort study in primary care.   Lancet. 1995;345(8961):1333-1338. doi:10.1016/S0140-6736(95)92537-6 PubMedGoogle ScholarCrossref
23.
Serrano-Ripoll  MJ , Meneses-Echavez  JF , Ricci-Cabello  I ,  et al.  Impact of viral epidemic outbreaks on mental health of healthcare workers: a rapid systematic review and meta-analysis.   J Affect Disord. 2020;277(August):347-357. doi:10.1016/j.jad.2020.08.034 PubMedGoogle Scholar
24.
Public Health England (PHE). PHE national influenza report: Summary of UK surveillance of influenza and other seasonal respiratory illnesses—06 August 2020—week 32 report. Accessed October 18, 2021. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/907349/National_Influenza_report_06_August_2020_week_32.pdf
25.
Accorsi  EK , Qiu  X , Rumpler  E ,  et al.  How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19.   Eur J Epidemiol. 2021;36(2):179-196. doi:10.1007/s10654-021-00727-7 PubMedGoogle ScholarCrossref
26.
Adhikari  S , Pantaleo  NP , Feldman  JM , Ogedegbe  O , Thorpe  L , Troxel  AB .  Assessment of community-level disparities in coronavirus disease 2019 (COVID-19) infections and deaths in large US metropolitan areas.   JAMA Netw Open. 2020;3(7):e2016938. doi:10.1001/jamanetworkopen.2020.16938 PubMedGoogle Scholar
27.
Liao  TF , De Maio  F .  Association of social and economic inequality with coronavirus disease 2019 incidence and mortality across US counties.   JAMA Netw Open. 2021;4(1):e2034578. doi:10.1001/jamanetworkopen.2020.34578 PubMedGoogle Scholar
28.
Ribeiro  WS , Bauer  A , Andrade  MCR ,  et al.  Income inequality and mental illness-related morbidity and resilience: a systematic review and meta-analysis.   Lancet Psychiatry. 2017;4(7):554-562. doi:10.1016/S2215-0366(17)30159-1 PubMedGoogle ScholarCrossref
29.
Allen  J , Balfour  R , Bell  R , Marmot  M .  Social determinants of mental health.   Int Rev Psychiatry. 2014;26(4):392-407. doi:10.3109/09540261.2014.928270 PubMedGoogle ScholarCrossref
30.
Office for National Statistics. Coronavirus (COVID-19) Infection Survey: characteristics of people testing positive for COVID-19 in England and antibody data for the UK. Accessed October 18, 2021. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/coronaviruscovid19infectionsinthecommunityinengland/december2020
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