Inequalities in Mortality Following SARS-CoV-2 Infection for People with Severe Mental Illness During and Following Vaccination Roll-out in England: a Retrospective, Whole-Country Linked Cohort Study.

BACKGROUND:People with severe mental illness (SMI) had a higher risk of death following SARS-CoV-2 infection compared with people without SMI during the COVID-19 pandemic peak. It is unclear whether this risk reduced in later stages after vaccination roll-out. We aimed to assess all-cause and cause-specific mortality following SARS-CoV-2 infection in people with or without SMI across pandemic stages, using whole-country data, while accounting for sociodemographic and clinical characteristics. METHODS:In this retrospective, whole-country cohort study, we analysed linked electronic health records for all people in England registered to primary care who were alive in November, 2019 (>99% of the population). The study population included people who had COVID-19 between Jan 31, 2020, and June 30, 2023, with information on deaths and vaccination. Data extracted from the NHS England Secure Data Environment provided through the British Heart Foundation Data Science Centre CVD-COVID-UK-COVID-IMPACT Consortium linked datasets were curated to form a dataset in July, 2024. Cox regression estimated differences in all-cause and COVID-19 mortality. Analyses were stratified by pandemic stages, defined by WHO policy and UK Government vaccination roll-out: Jan 31-Sept 30, 2020 (stage 1); Oct 1, 2020-July 18, 2021 (stage 2, vaccination roll-out); and July 19, 2021-June 30, 2023 (stage 3, post-vaccination roll-out). SMI comprised schizophrenia, schizoaffective disorder, bipolar disorder, or other affective and non-affective disorder with psychosis. A patient and public involvement panel was consulted during design phases of the study. FINDINGS:13 463 945 people with COVID-19 were identified, of whom 160 190 (1·19%) had SMI. People with SMI were older [mean age [SD], SMI 49·7 years [17·9], non-SMI 45·0 years [17·6]), had a similar sex split (females SMI vs non-SMI: 56·3% vs 56·6%); and were mostly White British (77·3% or 76·3%). People with SMI had higher all-cause mortality than those without (adjusted hazard ratio [aHR] 1·56, 95% CI 1·53-1·59). All-cause mortality risk in people with SMI was elevated in stage 1 (aHR 1·27, 95% CI 1·22-1·32), but larger in the stage 2 (aHR 1·56, 1·51-1·61) and stage 3 (aHR 1·55, 1·50-1·59). Vaccination prevalence was initially higher for people with SMI (in stage 2: 112 795 [73·2%, 95% CI 72·9-73·4], compared with people without SMI, 8 852 970 [67·4%, 67·3-67·4]). By study end, fewer people with SMI were fully vaccinated (127 145 [79·4%, 79·2-79·6]), compared with people without SMI (11 605 915 [87·2%, 87·2-87·3]. Higher COVID-19 mortality risk in people with SMI persisted but was partially attenuated by vaccination (aHR 1·25, 1·17-1·34). INTERPRETATION:Excess mortality in people with SMI persisted throughout the COVID-19 pandemic. Preventive public health and clinical strategies are needed to address excess mortality and lower vaccination. FUNDING:Health Foundation-Academy of Medical Sciences.