COVID-19 and Mental Illnesses in Vaccinated and Unvaccinated People
Authors: Walker Venexia M. , Patalay Praveetha , Cuitun Coronado Jose Ignacio , Denholm Rachel , Forbes Harriet , Stafford Jean , Moltrecht Bettina , Palmer Tom , Walker Alex , Thompson Ellen J. , Taylor Kurt , Cezard Genevieve , Horne Elsie M. F. , Wei Yinghui , Al Arab Marwa , Knight Rochelle , Fisher Louis , Massey Jon , Davy Simon , Mehrkar Amir , Bacon Seb , Goldacre Ben , Wood Angela , Chaturvedi Nishi , Macleod John , John Ann , Sterne Jonathan A. C. ,   Longitudinal Health and Wellbeing COVID-19 National Core Study, Lemanska Agnieszka , Kwong  Alex , Sampri Alexia , Rapala Alicja , Carnemolla Alisia , Hughes Alun , Green Amelia , Folarin Amos , Roberts  Amy , Goncalves Soares Ana , Steptoe Andrew , Wong Andrew , Boyd Andy , Gibson Andy , Knueppel  Anika , Shah Anoop , Campbell Archie , Kanagaratnam Arun , Karthikeyan Suseeladevi  Arun , Zheng  Bang , Raman Betty , Hou Bo , Wielgoszewska Bozena , Mackenna  Brain , Stewart Callum , Fang Chao , Bridger-Staatz Charis , Booth  Charlotte , Beckford Chelsea , Park Chloe , Steves Claire , Andrews Colm , McCartney  Daniel , Kopasker  Daniel , Foster Diane , Piehlmaier Dominik , Williams Dylan , Parker Edward , Rafeti  Elena , Lukaschuk  Elena , Tunnicliffe  Elizabeth , Badrick Ellena , Herrett Emily , Turner Emma L , McElroy Eoin , Almaghrabi  Fatima , Greaves Felix , McArdle Fintan , Glen Fiona , Perez-Reche Francisco , Griffith Gareth , Ploubidis George , Santorelli Gillian , Di Gessa Giorgio , Woodward Hannah , Curtis   Helen , Herbert Annie , Douglas Ian , Oakley Jacqui , Wild James M , Maddock Jane , Carpentieri JD , Morley Jess , Zhu Jingmin , Tazare John , Wright John , Kellas John , Kennedy Jonathan , Northstone Kate , Tilling Kate , Mansfield Kate  , Evans Katharine M , Mansfield  Kathryn , Willan Kathryn , Wang Kevin , Campbell Kirsteen C , Patel Kishan , Fox Laura , Sheard Laura , Saunders Laura C , Tomlinson Laurie , Hamill Howes Lee , Smeeth  Liam , Nigrelli Lidia , Nab Linda , Hopcroft  Lisa , Huntley Lizzie , Jones Louise , Finnigan  Lucy , Teece Lucy , Green  Mark , Crane Matthew , Freydin Maxim , Parker Michael , Green Michael , Kibble Milla , Cheetham Nathan , Timpson Nicholas , Hamilton Olivia , Zaninotto Paola , Garcia Paz , Jezzard Peter , Whitehorn Rebecca , Rhead Rebecca , Toms Renin , Thomas Richard , Silverwood Richard , Dobson Richard , Willans Robert , Flaig  Robin , McEachan Rosie , Mitchell Ruth , Bowyer Ruth , Costello Ruth , Parsons Sam , Berman Samantha , Ip Samantha , Baz Sarah , Walker Scott , Syed Ahmar Shah , Shaw Richard , Aziz Sheikh , Langan Sinead , Brophy  Sinead , Denaxas Spiros , Neubauer  Stefan , Piechnik  Stefan , McLachlan Stela , Smith  Stephen , Sharp Steve , North  Teri , Kromydas  Theocharis , Cowling Thomas , Yang Tiffany , Bolton  Tom , Ferreira  Vanessa , Katikireddi  Vittal , Mahalingasivam Viyaasan , Jacques Wels , Hulme William , Ranjan Yatharth , Sanders  Zeena-Britt 
Published: August 2024

ImportanceAssociations have been found between COVID-19 and subsequent mental illness in both hospital- and population-based studies. However, evidence regarding which mental illnesses are associated with COVID-19 by vaccination status in these populations is limited.ObjectiveTo determine which mental illnesses are associated with diagnosed COVID-19 by vaccination status in both hospitalized patients and the general population.Design, Setting, and ParticipantsThis study was conducted in 3 cohorts, 1 before vaccine availability followed during the wild-type/Alpha variant eras (January 2020-June 2021) and 2 (vaccinated and unvaccinated) during the Delta variant era (June-December 2021). With National Health Service England approval, OpenSAFELY-TPP was used to access linked data from 24 million people registered with general practices in England using TPP SystmOne. People registered with a GP in England for at least 6 months and alive with known age between 18 and 110 years, sex, deprivation index information, and region at baseline were included. People were excluded if they had COVID-19 before baseline. Data were analyzed from July 2022 to June 2024.ExposureConfirmed COVID-19 diagnosis recorded in primary care secondary care, testing data, or the death registry.Main Outcomes and MeasuresAdjusted hazard ratios (aHRs) comparing the incidence of mental illnesses after diagnosis of COVID-19 with the incidence before or without COVID-19 for depression, serious mental illness, general anxiety, posttraumatic stress disorder, eating disorders, addiction, self-harm, and suicide.ResultsThe largest cohort, the pre–vaccine availability cohort, included 18 648 606 people (9 363 710 [50.2%] female and 9 284 896 [49.8%] male) with a median (IQR) age of 49 (34-64) years. The vaccinated cohort included 14 035 286 individuals (7 308 556 [52.1%] female and 6 726 730 [47.9%] male) with a median (IQR) age of 53 (38-67) years. The unvaccinated cohort included 3 242 215 individuals (1 363 401 [42.1%] female and 1 878 814 [57.9%] male) with a median (IQR) age of 35 (27-46) years. Incidence of most outcomes was elevated during weeks 1 through 4 after COVID-19 diagnosis, compared with before or without COVID-19, in each cohort. Incidence of mental illnesses was lower in the vaccinated cohort compared with the pre–vaccine availability and unvaccinated cohorts: aHRs for depression and serious mental illness during weeks 1 through 4 after COVID-19 were 1.93 (95% CI, 1.88-1.98) and 1.49 (95% CI, 1.41-1.57) in the pre–vaccine availability cohort and 1.79 (95% CI, 1.68-1.90) and 1.45 (95% CI, 1.27-1.65) in the unvaccinated cohort compared with 1.16 (95% CI, 1.12-1.20) and 0.91 (95% CI, 0.85-0.98) in the vaccinated cohort. Elevation in incidence was higher and persisted longer after hospitalization for COVID-19.Conclusions and RelevanceIn this study, incidence of mental illnesses was elevated for up to a year following severe COVID-19 in unvaccinated people. These findings suggest that vaccination may mitigate the adverse effects of COVID-19 on mental health.