Heightened COVID-19 Mortality in People With Severe Mental Illness Persists After Vaccination

A Cohort Study of Greater Manchester Residents

Lamiece Hassan; Chelsea Sawyer; Niels Peek; Karina Lovell; Andre F. Carvalho; Marco Solmi; George Tilston; Matthew Sperrin; Joseph Firth

Disclosures

Schizophr Bull. 2023;49(2):275-284.

Abstract and Introduction

Abstract

Background and Hypothesis: Previous studies show that people with severe mental illness (SMI) are at higher risk of COVID-19 mortality, however limited evidence exists regarding risk postvaccination. We investigated COVID-19 mortality among people with schizophrenia and other SMIs before, during and after the UK vaccine roll-out.

Study Design: Using the Greater Manchester (GM) Care Record to access routinely collected health data linked with death records, we plotted COVID-19 mortality rates over time in GM residents with schizophrenia/psychosis, bipolar disorder (BD), and/or recurrent major depressive disorder (MDD) from February 2020 to September 2021. Multivariable logistic regression was used to compare mortality risk (risk ratios; RRs) between people with SMI (N = 193 435) and age–sex matched controls (N = 773 734), adjusted for sociodemographic factors, preexisting comorbidities, and vaccination status.

Study Results: Mortality risks were significantly higher among people with SMI compared with matched controls, particularly among people with schizophrenia/psychosis (RR 3.18, CI 2.94–3.44) and/or BD (RR 2.69, CI 2.16–3.34). In adjusted models, the relative risk of COVID-19 mortality decreased, though remained significantly higher than matched controls for people with schizophrenia (RR 1.61, CI 1.45–1.79) and BD (RR 1.92, CI 1.47–2.50), but not recurrent MDD (RR 1.08, CI 0.99–1.17). People with SMI continued to show higher mortality rate ratios relative to controls throughout 2021, during vaccination roll-out.

Conclusions: People with SMI, notably schizophrenia and BD, were at greater risk of COVID-19 mortality compared to matched controls. Despite population vaccination efforts that have prioritized people with SMI, disparities still remain in COVID-19 mortality for people with SMI.

Introduction

People with severe mental illness (SMI) die approximately 15 years younger than the general population, primarily due to the heightened morbidity and mortality from physical diseases among this vulnerable group.^[1–4] This elevated risk applies to both noncommunicable and infectious diseases and recent evidence from around the world—summarized in several recent systematic reviews and meta analyses^[5–11]—has now shown that people with SMI are also disproportionately affected by COVID-19.

While people with mental illnesses appear to be more vulnerable to COVID-19,^[5–11] the extent to which disparities in outcomes apply across different diagnostic groups of mental illness, and the reasons underpinning this, is a complex and dynamic subject, not fully elucidated by research. Available evidence points towards a combination of sociodemographic factors, preexisting comorbidities, and disease related factors (eg, psychotropic medication) as possible explanatory factors contributing towards increased risks of COVID-19 related infection, hospitalization, and mortality among people with SMI.^[5–8] Despite well-conducted and thorough studies, however, gaps and methodological limitations apply to several areas. For example, a recent systematic review of 23 studies on COVID-19 in mental illness reported that only a minority adjusted for preexisting conditions.^[7] Moreover, systematic reviews and meta-analyses have adopted varying search strategies and definitions of key variables, including COVID-19 infection itself, complicating efforts to synthesize knowledge in this area.^[8]

Two of the largest UK studies to date^[12,13] used the UK Biobank (UKB) cohort, a longitudinal cohort study linking primary care, hospital data, and death records for half a million older adults. These both reported higher rates of COVID-19 related hospitalization and mortality among people with mental illness, including schizophrenia, in the period prior to the UK vaccine roll-out. While considered a valuable resource, UKB participants are well known to be older, healthier and less ethnically diverse than the general population.^[14] Thus, while studies have generated some useful evidence, there remains a need to conduct research using more representative samples of the population, particularly those that include ethnically diverse groups and younger populations.

Concerns have led to calls for people with schizophrenia and certain other severe mental illnesses to be prioritized for access to vaccinations;^[15] advice which has been followed by several countries, including the United Kingdom.^[16] However, given the combination of biopsychosocial factors that may affect vaccine uptake and immune response among people with mental illness,^[17,18] evidence is still needed to demonstrate whether these disparities in COVID-19 mortality risks still persist following vaccination. In England, the NHS started administering COVID-19 vaccinations on December 8, 2020, with people with SMI prioritized for vaccination alongside people aged 70 years and over on advice from an independent expert advisory committee.^[19] By April 12, 2021, all people aged over 50 years (including SMI groups) had been offered a first vaccination; second vaccinations were offered 3–12 weeks after the individual's first dose. An early analysis of vaccination uptake nationally in England, albeit limited to patients over 80 up until March 17, 2021, showed that vaccination was initially lower among people with severe mental illnesses and learning disabilities.^[20] A more recent study by Bitan^[21] that followed up people with schizophrenia in Israel throughout the first year of the pandemic found that mortality rates declined in these populations following mass vaccination efforts, though they remained relatively higher compared to controls. The same study also noted that people with schizophrenia were less likely to be vaccinated.

In this study we aimed to examine COVID-19 related mortality among people with schizophrenia and other SMIs, compared to similar people without SMI, over a 20-month period (February 2020 to September 2021). This covered the period prior to, during, and after the initial vaccine roll-out in the United Kingdom. We also aimed to account for the influence of sociodemographic characteristics, preexisting clinical conditions, and vaccination status on the risks of COVID-19 related mortality among people with SMI. In doing so, we build upon previous studies to support enhanced understanding of the size and nature of the risks posed by COVID-19 to people with mental illness to inform public health strategies in a postvaccine world.

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Next Section

Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Baseline Sample Demographic Characteristics (as of January 31, 2020, Unless Otherwise Indicated) ^a
	Schizophrenia (N = 48 912)		Matched Control Group, SZ^b (N = 195 645)		BD^c (N = 13 932)		Matched Control Group, BD^b (N = 55 728)		MDD (N=152 489)		Matched Control Group, MDD^b (N = 609 953)
	n	%	n	%	n	%	n	%	n	%	n	%
Sex
Female	22 455	45.9	89 817	45.9	8340	59.9	33 360	59.9	93 212	61.1	372 848	61.1
Male	26 448	54.1	105 792	54.1	5 590	40.1	22 356	40.1	59 264	38.9	237 056	38.9
Age group
Mean, SD	50.7	19.6	50.7	19.6	50.0	16.2	50.0	16.2	50.4	16.0	50.4	16.0
Ethnicity
Asian	3663	7.5	16 103	8.2	820	5.9	4705	8.4	6929	4.5	50 855	8.3
Black	1576	3.2	5635	2.9	270	2.0	1744	3.1	2096	1.4	17 833	2.9
Mixed	861	1.8	2404	1.2	240	1.7	704	1.3	1590	1.0	7547	1.2
Other	4185	8.6	2 298 323 841	12.2	1055	7.1	6600	11.8	13 005	8.53	72 419	11.9
White	37 749	77.2	124 798	63.8	11 305	82.0	35 743	64.1	124 759	81.8	395 427	64.8
IMD decile
Mean, SD	3.3	2.6	4.3	2.9	3.7	2.8	4.3	2.9	3.8	2.8	3.8	2.8

^aCell counts and percentages may not add up to 100% of totals due to missing data and rounding (to 1 dp).
^bMatched on age (year of birth) and sex at birth.
^cCounts, except total, are rounded to base 5 for disclosure control purposes.

Table 2. Relative Risk (RR) of Mortality Due to COVID-19, by Diagnosis
Diagnosis	Deaths^a	Unadjusted^b	Adjusted^c
Diagnosis	n (%)	RR (95% CI)	aRR (95% CI)
Schizophrenia	1083 (2.2)	3.18 (2.94–3.44)*	1.61 (1.45–1.79)*
Matched control group for SZ	1402 (0.7)	–	–
BD	136 (1.0)	2.69 (2.16–3.34)*	1.92 (1.47–2.50)*
Matched control group for BD	207 (0.4)	–	–
MDD	926 (0.6)	1.59 (1.47–1.71)*	1.08 (0.99–1.17)
Matched control group	2352 (0.4)	–	–

^aIncludes all deaths.
^bIncludes deaths with month and year data.
^cIncludes deaths with month and year data. Adjusted for age, sex, ethnicity, deprivation (IMD decile), and preexisting comorbidities and vaccination status.
*Indicates p < .05.

Table 3. Adjusted ^a Multivariable Model for Relative Risk (RR) of Mortality Due to COVID-19, by Diagnosis
Variable	Schizophrenia aRR (95% CI)	BD aRR (95% CI)	MDD aRR (95% CI)
Mental illness status	1.61 (1.45–1.79)*	1.92 (1.47–2.50)*	1.08 (0.99–1.17)
Doubly vaccinated vs not vaccinated	0.76 (0.67–0.87)*	0.82 (0.59–1.16)	0.73 (0.66–0.81)*
Mental illness status* doubly vaccinated (interaction)	1.19 (0.97–1.44)	0.52 (0.28–0.97)*	0.91 (0.75–1.11)
Age (years)	1.09 (1.09–1.10)*	1.09 (1.08–1.10)*	1.10 (1.09–1.10)*
Female (ref) vs Male	1.22 (1.11–1.33)*	1.34 (1.07–1.68)*	1.32 (1.22–1.42)*
Ethnicity
White (ref) vs Asian	0.86 (0.70–1.07)	0.96 (0.57–1.62)	1.6 (0.99–1.36)
White (ref) vs Black	1.29 (0.99–1.68)	1.78 (0.96–3.31)	1.28 (0.99–1.64)
White (ref) vs mixed	1.25 (0.78–1.99)	1.55 (0.57–4.18)	1.17 (0.75–1.82)
White (ref) vs other	1.05 (0.92–1.19)	0.93 (0.64–1.36)	1.05 (0.94–1.18)
Deprivation^b	0.93 (0.92–0.95)*	0.92 (0.88–0.96)*	0.92 (0.91–0.93)*
Comorbidity
Alcohol misuse	1.41 (1.18–1.70)*	1.81 (1.24–2.64)*	1.70 (1.47–1.97)*
Atrial fibrillation	1.15 (1.03–1.29)*	1.25 (0.88–1.77)	1.24 (1.11–1.38)*
Cancer	1.57 (1.44–1.70)*	1.40 (1.11–1.77)*	1.75 (1.62–1.89)*
CKD	1.19 (1.08–1.30)*	1.09 (0.82–1.44)	1.23 (1.12–1.34)*
Chronic liver disease	1.33 (0.99–1.78)	1.76 (0.94–3.29)	1.80 (1.46–2.21)*
COPD	1.56 (1.39–1.74)*	1.50 (1.11–2.02)*	1.57 (1.43–1.73)*
CHD	1.13 (1.02–1.25)*	0.96 (0.70–1.32)	1.01 (0.92–1.11)
Dementia	2.40 (2.16–2.67)*	2.81 (2.07–3.83)*	3.39 (3.07–3.73)*
Diabetes	0.99 (0.91–1.08)	1.25 (0.99–1.58)	1.06 (0.98–1.15)
Epilepsy	1.45 (1.18–1.78)*	0.82 (0.42–1.62)	1.29 (1.03–1.60*
Heart failure	1.42 (1.24–1.62)*	1.80 (1.22–2.69)*	1.50 (1.32–1.71)*
Learning disability	2.79 (2.01–3.87)*	1.87 (0.69–5.09)	3.53 (2.43–5.15)*
Multiple sclerosis	1.49 (0.71–3.12)	2.24 (0.56–0.90)*	1.73 (1.07–2.79)*
Parkinson's disease	1.66 (1.31–2.11)*	1.75 (0.89–3.45)	1.46 (1.09–1.97)*
Peripheral vascular disease	1.26 (1.06–1.50)*	1.80 (1.17–2.78)*	1.65 (1.43–1.89)*
Stroke	1.17 (1.06–1.29)*	1.33 (0.99–1.79)	1.34 (1.22–1.47)*
Substance misuse	1.55 (1.29–1.87)*	1.52 (1.01–2.29)*	1.56 (1.31–1.87)*

^aAdjusted for demographic variables plus atrial fibrillation, cancer, chronic kidney disease (CKD), chronic liver disease, chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), dementia, diabetes, epilepsy, heart failure, learning disability, multiple sclerosis, Parkinson's disease, peripheral vascular disease, and stroke.
^bLower deciles indicate higher levels of deprivation.
*Indicates p < .05.