Patients with severe mental health issues may face a significantly higher risk of mortality from infectious diseases compared with the general population, according to a new study.
In the comprehensive systematic review and meta-analysis, published in eClinicalMedicine, investigators analyzed 29 observational cohort studies from high-income countries, encompassing data on hundreds of thousands of patients with severe mental illness (SMI) diagnoses, including schizophrenia, bipolar disorder, and other psychoses.
The meta-analysis included studies published up to June 2024, with sample sizes of patients with SMI ranging from 200 to 1.1 million and follow-up periods from 2 to 40 years. The majority of the studies (n = 23/29) focused on schizophrenia, schizoaffective disorder, and other psychoses, whereas 9 of them included bipolar disorder.
The investigators conducted a systematic search of PubMed, Web of Science, PsycINFO, and EMBASE databases. Studies were included if they assessed mortality from any infection (excluding COVID-19 infections) in adults with SMI compared with the general population, or non-SMI controls. The Newcastle-Ottawa Scale was used to assess study quality, with 58.6% of included studies rated as good quality.
Random-effects meta-analyses were performed using inverse variance models. Heterogeneity was assessed using Higgin’s I2, and sources of heterogeneity were investigated through subgroup analyses and metaregression. Publication bias was evaluated using funnel plots and Egger’s tests.
Among the key findings were:
- Patients with SMI had 2.71 times higher risk of mortality from infectious diseases broadly (95% confidence interval [CI] = 2.33–3.16), though significant heterogeneity (I2 = 68.2%) was observed across the studies.
- The risk of mortality from respiratory infections was 3.27 times higher (95% CI = 2.57–4.17) with high heterogeneity (I2 = 98.9%).
- Pneumonia mortality risk was particularly elevated, with a 4.15 times higher risk (95% CI = 3.42–5.04).
- No significantly increased risk of sepsis mortality was found overall (relative risk [RR] = 1.54, 95% CI = 0.72–3.27), though subgroup analysis revealed an increased risk when comparing patients who had SMI with the general population (RR = 2.81, 95% CI = 1.29–6.16).
- The risk of mortality from other infection types was 1.80 times higher (95% CI = 1.35–2.39), with substantial heterogeneity (I2 = 60.2%).
The investigators found that patients with SMI were more than twice as likely to die from infectious diseases overall and more than three times as likely to die from respiratory infections, particularly pneumonia.
Additional results included:
- Infectious diseases mortality: Pooled RR = 2.71 (95% CI = 2.33–3.16) based on 24 analyses from 14 studies (N = 739,852). Men showed the highest risk (RR = 3.55, 95% CI = 2.58–4.89), while women had lower risk (RR = 2.14, 95% CI = 1.70–2.71).
- Respiratory infection mortality: Pooled RR = 3.27 (95% CI = 2.57–4.17) based on 18 analyses from 14 studies (N = 1.4 million), with a particularly high pneumonia-specific risk (RR = 4.15, 95% CI = 3.42–5.04).
- Sepsis mortality: No significant increased risk overall (RR = 1.54, 95% CI = 0.72–3.27), though increased risk was observed when comparing patients who had SMI with the general population (RR = 2.81, 95% CI = 1.29–6.16).
- Other infection types mortality: Pooled RR = 1.80 (95% CI = 1.35–2.39) based on 8 analyses from 4 studies (N = 93,743).
The study highlighted several possible mechanisms for the increased infection mortality risk in SMI, including health inequalities, reduced access to health care, mental illness stigma, comorbidities, health behaviors like smoking and substance use, antipsychotic medication effects, and immune abnormalities associated with SMI.
The investigators noted that high heterogeneity across the studies warranted cautious interpretation of the results. They also emphasized the exclusion of data from low- and middle-income countries, limiting the generalizability of findings to regions where infectious diseases significantly contributed to overall mortality rates.
The investigators recommended prioritizing patients with SMI for preventive strategies, including influenza and pneumococcal vaccines, and suggested closer medical monitoring for those with SMI diagnosed with certain infections, particularly pneumonia.