COVID-19 Prevalence and Mortality Among Schizophrenia Patients

A Large-Scale Retrospective Cohort Study

Dana Tzur Bitan; Israel Krieger; Khalaf Kridin; Doron Komantscher; Yochai Scheinman; Orly Weinstein; Arnon Dov Cohen; Assi Albert Cicurel; Daniel Feingold


Schizophr Bull. 2021;47(5):1211-1217. 

In This Article


In this study, we assessed the odds for hospitalization and mortality due to COVID-19 in a large sample of individuals with schizophrenia and an age-and-sex matched group of controls. The results of the analyses indicated that individuals with schizophrenia were significantly more likely to be tested for COVID-19 and less likely to receive a positive diagnosis of COVID-19. Nonetheless, they were twice as likely to be hospitalized due to the disease and 3 times more likely for COVID-19 mortality compared to controls. These associations were sustained even after adjusting for marital status, sector, socioeconomic status, smoking, obesity, diabetes, hyperlipidemia, COPD, and IHD.

Contrary to our initial hypothesis, individuals with schizophrenia were tested more frequently, and were less likely to test positive for COVID-19. These results also contradict previous predictions, which foresaw higher rates of infection within this population.[4,21,22] Furthermore, in a recent case-control study conducted in the United States,[23] the authors reported significantly higher odds (9.89) of COVID-19 infection among recently diagnosed schizophrenia patients (within the past year), with lower odds (1.48) in patients with a lifetime diagnosis of schizophrenia. One potential explanation to account for these differences in rates of infection may be related to the medical policies employed by the Israeli Ministry of Health. The fact that patients with schizophrenia were tested more frequently than the controls may be associated with the mandatory testing policy implemented in psychiatric institutes and outpatient clinics in Israel, which require patients to be tested prior to hospital admission and/or psychiatric care. This policy of early COVID-19 detection may also have been applied in sheltered community homes and supervised rehabilitation centers, and may account for the lower prevalence in positive cases among the schizophrenia group. Future studies should explore whether facilities with such mandatory policy have differential infection rates, and whether inpatients and outpatients differ in odds for infection and morbidity. Another potential explanatory mechanism to account for the lower rates of infection is that social isolation, as well as the fact that the majority of individuals with schizophrenia were unmarried and less likely to have been infected by family members (which are considered to be one of the main routes of infection[24,25]), may resulted in reduced chances of infection. Such competing hypotheses should be subjected to future research.

Despite being tested more and having lower infection rates, our findings indicate that individuals with schizophrenia are significantly more likely to require intensive medical care, as reflected by the higher rates of hospitalization. These findings correspond to those reported by Wang et al,[23] who found higher rates of COVID-19 hospitalizations among patients with severe mental illnesses in the United States. It has been previously offered that biological factors related to neuroinflammation may contribute to the association between psychiatric disturbances and COVID-19,[26] mainly in patients with a new onset of psychiatric symptoms. An additional explanation to account for the higher rates of hospitalization is related to medical, behavioral, and environmental risk factors. Schizophrenia patients are more likely to suffer from comorbid medical conditions[27] and suffer from social isolation, which may interfere with early help-seeking behavior.[28] As a consequence, they may present themselves for medical care only when their condition has already worsened. This, as well as lower access to knowledge and lack of access to quality preventative services,[29] might explain the more severe trajectory of illness exhibited by these patients. Such potential pathways should be subjected to future research.

The higher COVID-19 mortality rates detected among schizophrenia patients align with previous predictions regarding the potential adverse consequences of high physical comorbidity among these patients.[4] Schizophrenia patients were more likely to be diagnosed with obesity, smoking, diabetes, hyperlipidemia, and COPD, and significantly less likely to receive a diagnosis of IHD. These findings correspond with previous reports.[16] Previous studies have also demonstrated a pattern of higher IHD mortality, yet lower or no increased risk of IHD in schizophrenia,[16,30] a finding that has been suggested to be associated with lower help-seeking behavior.[31–33] The higher rates of mortality also confirm the results reported by Fond et al,[10] who found a significantly higher prevalence of schizophrenia diagnoses among individuals admitted to acute care hospitals in France. Previous studies have indicated that aside from baseline physical comorbid illnesses, schizophrenia patients engage in smoking behavior more frequently and are therefore more vulnerable to smoking-related illnesses such as COPD,[16] which is considered a risk factor for COVID-19 mortality. These results highlight the convergence of several prominent risk factors for COVID-19 mortality among schizophrenia patients, as well as the need to address modifiable risk factors via adequate preventative interventions.

The findings of this study have several important clinical and empirical implications. Although the findings indicate a higher mortality risk among schizophrenia patients, the absolute number of deaths (22 in the schizophrenia group, 7 in the controls) and hospitalizations (162 in the schizophrenia group and 72 in the controls) was low. As the odds of significant COVID-19 morbidity and mortality among schizophrenia patients were high even after adjusting for clinical factors, future studies should further explore additional explanatory routes that might lead to detrimental outcomes among this population. Such routes may be associated with potential medications and side effects,[34] factors contributing to illness management, and factors related to quality healthcare. Clinically, the results of the study stress the need to focus intervention efforts on modifiable factors that might minimize mortality rates among these patients.

Several limitations should be noted. The study population comprised patients with a schizophrenia diagnosis and cases which were matched by age and sex. Thus, the sample utilized in this study is not a representative sample. The present study focused on the presence of associations between schizophrenia and COVID-19 morbidity and mortality, and therefore no conclusive inferences can be made regarding causality. Although this is a large-scale study, the relatively small number of deceased individuals does not allow for sufficient statistical power to characterize specific factors associated with mortality among individuals with schizophrenia, and further studies are needed in order to allow for statistical inference of these effects. The CHS registry does not contain information about severity of schizophrenia; therefore, the pattern of associations between COVID-19 morbidity and mortality across different severity levels should be subjected to future research. The database utilized in this study was mined in 2017; therefore, individuals who were diagnosed with schizophrenia within the last 3 years were not included in this analysis. Future studies can determine whether the results reported in this study replicate across patients with a recent schizophrenia diagnosis. Finally, our study did not address the number of comorbid medical conditions presented by patients, which may be an additional risk factor for hospitalization and mortality.[35] Despite these limitations, the results of the current study clearly indicate that individuals with schizophrenia are a population-at–risk for hospitalization and mortality due to COVID-19. Thus, efforts should be made to develop and implement preventative programs aimed at minimizing risks among this population.