COVIDMENT study analysis
Of the 403,794 individuals included in the participating COVIDMENT cohort studies, 325,298 individuals met the eligibility criteria for the present study (Supplementary Fig. 1). Over half of the overall study population (65.1%), and of each participating cohort, were female (Supplementary Table 8). The mean age in the participating cohorts ranged from 36.9 years (MAP-19) to 59.4 years (CovidLife), with a mean of 48 years in the overall study population.
The proportion of females was higher among individuals with (72.0%) vs. without (60.9%) a diagnosis of any mental illness, while the mean age was higher among those with (48.5 (SD: 1.8) years) vs. without (47.8 (SD: 3.6) years) such diagnosis (Table 1). The proportion of individuals with a previous COVID-19 infection was similar between the two groups (2.5% and 2.3% respectively), while the proportions of individuals who smoked or had ≥1 chronic physical condition were higher among those with (21.5% smoked, 66.9% had ≥1 chronic physical condition) vs. without (17.0% smoked, 36.8% had ≥1 chronic physical condition) a diagnosis of any mental illness. Low levels of missing data were observed for the majority of covariates.
Table 1 Distribution of sociodemographic variables in the included COVIDMENT study population, overall and by diagnosis of any mental illness diagnosis, presented as N (%) or mean (SD)
314,827 individuals were included in the analysis of uptake of the first dose of a COVID-19 vaccine by 30th September 2021 (Table 2). Overall vaccination uptake was high (85.1%; n = 267,981/314,827). However, a small difference in uptake was observed between individuals with (82.4%; n = 99,041/120,212) vs. without (86.8%; n = 168,174/193,706) any mental illness. Vaccination uptake in each included cohort is displayed in Supplementary Table 9.
Table 2 Uptake of COVID-19 vaccination overall and by diagnosis of any mental illness diagnosis, in the included COVIDMENT study population, presented as N (%)
Results from the meta-analysis showed no significant association, after adjustment for covariates, between the diagnosis of any mental illness and uptake of the first dose by 30th September 2021 in the overall study population (pooled PR: 0.99, 95% CI: 0.97- 1.00); I2: 91.7%, p < 0.001) or among males and females separately (Fig. 1A, Supplementary Fig. 2A, Supplementary Table 10). Although the level of heterogeneity was high, a statistically significant association between the diagnosis of any mental illness and lower uptake of the first dose was only found in cohort-specific results from EstBB-EHR (PR: 0.97, 95% CI: 0.96–0.97) and MAP-19 (PR: 0.93, 95% CI: 0.88–0.98). No associations were observed between anxiety or depressive symptoms and uptake of the first dose by 30th September 2021 in the overall study population. However, the sex-stratified analyses showed small but significant associations between anxiety (pooled PR: 0.97, 95% CI: 0.96–0.99; I2: 0.0%, p > 0.05) and depressive symptoms (pooled PR: 0.98, 95% CI: 0.96–0.99; I2: 0.0%, p > 0.05) and lower uptake of the first dose among males, but not females (Supplementary Fig. 2A, Supplementary Table 10).
Fig. 1: Prevalence ratio (PR) and 95% confidence intervals (CI) of COVID-19 vaccine uptake, according to the presence of any mental illness diagnosis, anxiety symptoms or depressive symptoms, in the included COVIDMENT study population.
A first dose of a COVID-19 vaccine by 30th September 2021, (B) first dose of a COVID-19 vaccine by 18th February 2022, (C) second dose of a COVID-19 vaccine by 18th February 2022. Data are presented as PR with 95% CIs (horizontal lines), rounded to 2 decimal places. Cohort-specific estimates are adjusted for age, sex, previous COVID-19 infection, smoking, and physical comorbidity status (except MAP-19 models, which are adjusted for age, sex, and previous COVID-19 infection only). The ‘overall’ estimates are derived from the random effects meta-analyses of the cohort-specific estimates. EstBB cohorts (EstBB-C19 = The Estonian Biobank COVID-19 Cohort; EstBB-EHR = The Estonian Biobank electronic health records); C19-Resilience = The Icelandic COVID-19 National Resilience Cohort; MAP-19 = The Norwegian COVID-19, Mental Health and Adherence Project; MoBa = The Norwegian Mother, Father and Child Cohort Study). Total N (any mental illness diagnosis; anxiety symptoms: depressive symptoms) = (A) 295,319; 113,002; 110,322; (B) 294,647; 112,025; 108,949; (C) 246,043; 94,830; 92,215.
Results from sensitivity analyses which excluded cohorts using electronic health records for the definition of exposure and/or outcome, or excluded individuals with any chronic physical condition, also showed no significant difference in uptake of the first dose by 30th September 2021 between those with vs. without a diagnosis of any mental illness (Supplementary Table 11). Additionally, results from the third sensitivity analysis, which explored potential differences related to national COVID-19 mitigation strategies and vaccination policies, showed very similar patterns in the Nordic and non-Nordic country groups, with no significant association between a diagnosis of any mental illness and vaccine uptake observed in either group.
Uptake of the first dose of a COVID-19 vaccine by 18th February 2022 was analysed in 313,584 individuals. Vaccination uptake was high (88.9%; n = 278,887/313,584); however, a small difference in uptake remained between individuals with (86.7%; n = 103,955/119,908) vs. without (90.3%; n = 174,612/193,340) mental illness (Table 2).
Results from the meta-analysis revealed a small association, after adjustment for covariates, between the diagnosis of any mental illness and first dose uptake by 18th February 20222 in the overall COVIDMENT study population (pooled PR: 0.99, 95% CI: 0.98–0.99; I2: 80.0%, p < 0.001) and among females separately (pooled PR: 0.98, 95% CI: 0.98–0.99; I2: 76.7%, p < 0.001), but not males (Fig. 1B, Supplementary Table 10, Supplementary Fig. 2B). No association was observed between anxiety or depressive symptoms and vaccination uptake in the overall study population or among males or females seperately. However, results from the MoBa cohort showed that uptake was slightly lower among individuals with vs. without anxiety (PR: 0.97, 95% CI: 0.96–0.99) or depressive (PR: 0.98, 95% CI: 0.97–0.99) symptoms.
Results from the first two sensitivity analyses showed no signficiant difference in first dose uptake by 18th February 2022 among individuals with vs. without a diagnosis of any mental illness (Supplementary Table 11). Although the results for both Nordic (pooled PR: 0.99, 95% CI: 0.99–1.00; I2 :18.2%, p > 0.05) and non-Nordic (pooled PR: 0.98, 95% CI: 0.97–0.99, I2: 67.4%, p < 0.05) country groups were very similar, the association between a diagnosis of any mental illness and vaccine uptake was only statistically significant in the latter group.
264,404 individuals were eligible for the analysis of uptake of the second dose of a COVID-19 vaccine by 18th February 2022 (Table 2). Among these individuals, vaccination uptake was very high (95.5%; n = 252,439/264,404) and the difference in uptake between those with (94.7%; n = 93,420/98,671) vs. without (95.9%; n = 158,830/165,542) any mental illness was very small. Due to low numbers of participants, models could not be run in the MAP-19 and CovidLife cohorts.
The meta-analysis of the remaining eligible cohorts showed no significant differences, after adjustment for covariates, in second dose uptake by the diagnosis of any mental illness or the presence of anxiety or depressive symptoms in the overall study population or among males or females separately (Fig. 1C, Supplementary Table 10, Supplementary Fig. 2C). Sensitivity analysis results also showed no signficant difference in vaccination uptake among those with vs. without a mental illness diagnosis (Supplementary Table 11).
Swedish register study analysis
Among the 8,080,234 individuals included in the Swedish register study population, individuals with a specialist diagnosis of any mental illness were more likely to be female (55.7% vs. 49.6%) and younger (45.2 years vs. 50.2 years), compared to those without such diagnosis (Table 3). Individuals with a mental illness diagnosis had a lower prevalence of university education (28.7% vs. 38.5%), were less likely cohabiting (22.3% vs. 42.5%) or in the highest quartile of income (13.0% vs. 25.8%), and had a higher prevalence of chronic physical conditions, as denoted by a CCI of ≥1 (19.0% vs. 11.0%). Although the prevalence of severe COVID-19 infection was low in the overall study population (0.4%), the prevalence was higher among individuals with (0.8%) vs. without (0.3%) any mental illness diagnosis. The proportion of missing data for all covariates was low ( ≤2.5%).
Table 3 Distribution of sociodemographic variables in the included Swedish register study population, overall and by specialist diagnosis of any mental illness, presented as N (%) or mean (SD)
In this study population, uptake of the first dose of a COVID-19 vaccine by 30th September 2021 was high (84.6%; n = 6,834,074/8,080,234) (Table 4). However, vaccination uptake was slightly lower in individuals with (78.5%; n = 387,341/493,705) vs. without (85.0%; 6,446,733/7,586,529) a specialist diagnosis of any mental illness. Vaccination uptake in relation to each type of mental illness diagnosis and type of psychiatric medication used is shown in Supplementary Table 12.
Table 4 Uptake of COVID-19 vaccination overall, and by specialist diagnosis of any mental illness and prescribed use of any psychiatric medication, in the included Swedish register population, presented as N (%)
Taking into account all covariates, we found that uptake of the first dose in individuals with any mental illness was 1% lower than that of individuals without a mental illness (PR: 0.99, 95% CI: 0.99–0.99, p < 0.001) (Fig. 2A). Similarly small differences in first dose uptake were shown for most types of mental illness, except for substance use disorder which had the strongest association with lower vaccination uptake (PR: 0.84, 95% CI: 0.84–0.85, p < 0.001), and depression (PR: 1.02, 95% CI: 1.02–1.02, p < 0.001) and bipolar disorder (PR: 1.04, 95% CI: 1.03–1.04, p < 0.001), for which significantly higher vaccination uptake was found. No significant associations were found for tobacco use disorder or anxiety. A 3% higher uptake was observed among individuals with prescribed use of any psychiatric medication, compared to individuals not using such medication (PR: 1.03, 95% CI: 1.03–1.03, p < 0.001). Similar associations were found for different types of psychiatric medication. Sex-stratified analyses revealed a significant association between the diagnosis of any mental illness and lower first dose uptake among males (PR: 0.97, 95% CI: 0.97–0.98, p < 0.001), but not females. The results did not differ substantially among individuals with vs. without chronic physical conditions (Supplementary Table 13).
Fig. 2: Prevalence ratio (PR) and 95% confidence intervals (CI) of COVID-19 vaccine uptake, according to specialist diagnosis of mental illness and prescribed use of psychiatric medication, in the Swedish register study population.
A first dose of a COVID-19 vaccine by 30th September 2021 and (B) second dose of a COVID-19 vaccine by 30th November 2021. Data are presented as PR with 95% CIs (horizontal lines), rounded to 2 decimal places. All estimates are adjusted for age, sex, region of residence, highest educational attainment, cohabitation status, income, severe COVID-19 infection and the Charlson Comorbidity Index (CCI). Substance use disorder excludes alcohol and tobacco use disorders. N = (A) 7,883,298; (B) 6,728,266.
Results from the multi-level exposure analysis showed that, compared to individuals with neither any specialist mental illness diagnosis nor prescribed use of any psychiatric medication, uptake of the first dose was 3% higher among those with prescribed use of any psychiatric medication but no specialist diagnosis (PR: 1.03, 95% CI: 1.03–1.03, p < 0.001), and 1% higher among those with both a specialist diagnosis and prescribed use of any psychiatric medication (PR: 1.01, 95% CI: 1.01–1.01, p < 0.001) (Fig. 3A). However, those with a specialist diagnosis of any mental illness but no prescribed use of any psychiatric medication had a 9% reduction in first dose uptake (PR: 0.91, 95% CI: 0.91–0.91, p < 0.001). This pattern was also observed for the multi-level exposure analysis carried out for anxiety, depression, and psychotic disorder, with a particularly low uptake of vaccination among individuals with psychotic disorder but no medication use (PR: 0.78, 95% CI: 0.76–0.79, p < 0.001).
Fig. 3: Prevalence ratio (PR) and 95% confidence intervals (CI) of COVID-19 vaccine uptake, according to specialist diagnosis of mental illness/prescribed medication status, in the Swedish register study population.
A first dose of a COVID-19 vaccine by 30th September 2021 and (B) second dose of a COVID-19 vaccine by 30th November 2021. Data are presented as PR with 95% CIs (horizontal lines), rounded to 2 decimal places. All estimates are adjusted for age, sex, region of residence, highest educational attainment, cohabitation status, income, severe COVID-19 infection and the Charlson Comorbidity Index (CCI). N = (A) 7,883,298; (B) 6,728,266.
6,834,054 individuals were eligible for the analysis of the uptake of the second dose of a COVID-19 vaccine by 30th November 2021 (Table 4). Vaccination uptake in the overall study population was very high (98.1%; n = 6,704,293/6,834,054), and the difference between those with (96.2%; n = 372,437/387,340) vs. without (98.2%; n = 6,331,856/6,446,714) a specialist diagnosis of any mental illness was very small.
Accordingly, model results showed very small differences in second dose uptake among those with vs. without a specialist diagnosis of any mental illness (PR: 0.99, 95% CI: 0.99–0.99, p < 0.001) or prescribed use of any psychiatric medication (Fig. 2B). This was also observed for all types of mental illness diagnosis (e.g. PR for substance use disorder: 0.94, 95% CI: 0.94–0.95, p < 0.001), PR for psychotic disorder: 1.00, 95% CI: 0.99–1.00, p < 0.001) and all types of psychiatric medication. Results from the stratified analyses showed no substantial differences in the associations by sex or the presence of chronic physical conditions (Supplementary Table 13). Simiarly, the multi-level exposure analysis showed statistically significant, but very small, differences in second dose uptake according to specialist diagnosis and/or prescribed medication use (Fig. 3B).