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

Importance

Associations 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.

Objective

To determine which mental illnesses are associated with diagnosed COVID-19 by vaccination status in both hospitalized patients and the general population.

Design, Setting, and Participants

This 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.

Exposure

Confirmed COVID-19 diagnosis recorded in primary care secondary care, testing data, or the death registry.

Main Outcomes and Measures

Adjusted 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.

Results

The 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 Relevance

In 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.