It is safe to say that COVID-19 has become a prominent part of our lives over the last year. Since the deadly virus first appeared, it has caused unprecedented challenges to the health care system all around the world, changed our day-to-day lives, and been consistently discussed and researched.

Thanks to the impressive amount of research on COVID-19, we have learned a lot about the illness and the factors that increase the risk of infection and mortality, which is especially important to guide clinical decision-making and target enhanced protective measures.

To date, the identified risk factors include a wide range of medical issues, and there has been growing attention to differences in outcomes by socioeconomic status and race. Consequently, it seems likely that the pandemic has deepened existing health inequalities.

Recent evidence also suggests that our mental health is affected by the pandemic and that existing inequalities have been made worse. However, less attention has been paid to whether pre-existing mental health difficulties can put people at a higher risk for COVID-19. Studies have reported an increased incidence of COVID-19 among patients with psychiatric disorders (Wang et al., 2020; Taquet et al., 2020), increased mortality risk in broadly defined groups of patients with any psychiatric disorder (Wang et al., 2020; Li et al., 2020), and a higher risk of adverse outcomes for patients with severe mental illness (Lee et al., 2020).

Although findings may suggest that psychiatric illness is a risk factor for contracting and dying from the virus, specific diagnoses were not examined. It is important to identify patients at an increased risk of adverse outcomes, including mortality as outcomes may vary by diagnosis. Therefore, in the study summarised below, Nemani and colleagues (2021) aimed to assess whether a diagnosis of a schizophrenia spectrum disorder, mood disorder, or anxiety disorder is associated with mortality in patients with COVID-19.

Methods

This retrospective cohort study assessed 7,348 adult patients (mean age 54; 53% female) with a laboratory-confirmed COVID-19 diagnosis, in a large medical system in New York.

Researchers classified the diagnoses of the cohort based on the International Classification of Diseases (ICD-10) before their testing date by schizophrenia spectrum disorders, mood disorders, and anxiety disorders. Of all patients included in the study, 1.0% had a history of a schizophrenia spectrum illness, 7.7% had a history of a mood disorder, and 4.9% had a history of an anxiety disorder.

Patients with these diagnoses were compared with a reference group (N=6,349) without psychiatric disorders.

The main study outcome was the risk of death or hospital discharge to hospice ≤ 45 days after a positive test result for SARS-CoV-2.

The researchers associated this outcome with these antecedent mental health diagnoses and adjusted their analysis to account for age, sex, race, smoking status, and a long list of established medical risk factors including hypertension, heart failure, diabetes, myocardial infarction, chronic kidney disease, chronic obstructive pulmonary disease, and cancer.

Results

Patients with a history of mental health diagnoses had a slightly lower rate of positive testing for COVID-19 compared to the control group.

After adjusting for demographic characteristics and medical factors, a premorbid diagnosis of schizophrenia spectrum disorder was significantly associated with mortality (odds ratio [OR], 2.67; 95% CI, 1.48 to 4.80). In other words, people with schizophrenia were found to have 2.7 times the odds of dying from COVID-19 when compared to people without a psychiatric disorder. However, diagnoses of mood disorders (OR, 1.14; 95% CI, 0.87 to 1.49) and anxiety disorders (OR, 0.96; 95% CI, 0.65 to 1.41) were not significantly associated with mortality after adjustment.

In comparison with other risk factors, a diagnosis of schizophrenia ranked high up, and it was only years of age that had a stronger association with mortality.

Conclusions

The most notable finding from this study is that people with psychiatric illness, specifically schizophrenia, may be at a greater risk of dying from COVID-19, even after controlling for age, race, and various medical issues. In fact, the results indicate that people with schizophrenia are the second highest risk group for dying from COVID-19, after older age.

The question remains, why?

Schizophrenia has been associated with decreased life expectancy by as much as 10-20 years less than the general population (WHO, 2009). Beyond social and lifestyle factors, systemic barriers, and delayed treatment, people with schizophrenia may be more susceptible to COVID-19 mortality due to biological factors related to their psychiatric illness or treatment. Immune dysregulation and inflammatory problems associated with schizophrenia could be increasing severity of reactions to COVID-19 (Stefansson et al., 2009; Steiner et al., 2010)., and antipsychotic medication has been associated with a higher risk of mortality from respiratory illness (Wang et al., 2017).

Strengths and limitations

This is a very important, reasonably robust, and carefully conducted study. The researchers included a relatively large sample of demographically diverse patients from several sites in the NYC health care system, and the prevalence of psychiatric diagnoses in the sample was consistent with what would be expected based on nationwide prevalence (Del Valle et al., 2020). A period of 45 days was allowed for a follow-up to ensure that most patients had reached a primary outcome by the end of the study. Importantly, the authors attempted to control for as many potentially relevant confounding factors as possible, such as age, ethnicity, and a wide range of medical issues.

However, the study had several limitations:

• Firstly, the accuracy of clinical psychiatric diagnoses could not be validated in all patients, and psychiatric disorders were grouped together into broader categories, which means that there may have been differences in risk associated with specific diagnoses within these categories.
• Secondly, it should be borne in mind that the number of patients with schizophrenia in this study was very small (n=75) and therefore, though plausible, the findings should be interpreted with caution.
• Thirdly, the study took place in a large healthcare system in the US during a peak of the COVID-19 pandemic, which does not reflect clinical practice in other contexts. As such, the generalisability of the findings to other patient populations and health care systems is uncertain.
• Last but not least, although the authors controlled for many factors that may be associated with a higher risk of COVID-19 mortality, they did not address some known risk factors, such as obesity. The use of psychotropic medications at the time of the infection were also not assessed and may have been associated with either harmful or protective effects. Importantly, the study does not account for the wide range of social, cognitive, and behavioural disadvantages that schizophrenia usually infers. While it is important to consider biological predispositions inherent to the condition, it is important to acknowledge the health and social inequalities to which patients with long-term psychiatric disorders, such as schizophrenia, are prone.

Implications

We certainly need to replicate this study using larger samples to confirm that people with schizophrenia may be at increased risk of dying from COVID-19, as well as to understand the immune mechanisms and the potential effects of specific psychotropic medications underlying these findings.

Nonetheless, the findings are alarming and have some major implications. Specifically, if people with schizophrenia are a high-risk group they could, therefore, be prioritised for vaccination, testing, and medical care. Clinicians should aim to improve patient education and awareness, encourage adherence to COVID-19 prevention measures and facilitate vaccine uptake.

Lastly, people with schizophrenia may be caught in a vicious cycle whereby their mental illness increases their risk of adverse outcomes from COVID-19, while at the same time, COVID-19 worsens their psychiatric condition. Targeted interventions may be needed for patients with severe mental illness to prevent worsening health disparities.

Statement of interests

None.

Links

Primary paper

Nemani, K., Li, C., Olfson, M., Blessing, E. M., Razavian, N., Chen, J., … & Goff, D. C. (2021). Association of psychiatric disorders with mortality among patients with COVID-19. JAMA psychiatry, 78(4), 380-386.

Other references

Wang Q, Xu R, Volkow ND. Increased risk of COVID-19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States. [published online October 7, 2020].World Psychiatry. 2020.  https://doi.org/10.1002/wps.20806

Taquet M, Luciano S, Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psychiatry. Published online November 9, 2020. DOI: https://doi.org/10.1016/S2215-0366(20)30462-4

Li L, Li F, Fortunati F, Krystal JH. Association of a prior psychiatric diagnosis with mortality among hospitalized patients with coronavirus disease 2019 (COVID-19) infection. JAMA Netw Open. 2020;3 (9):e2023282. doi: 10.1001/jamanetworkopen.2020.23282

Lee SW, Yang JM, Moon SY, et al. Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: a nationwide cohort study. Lancet Psychiatry. 2020;7(12):1025- 1031. DOI: https://doi.org/10.1016/S2215-0366(20)30421-1

Stefansson H, Ophoff RA, Steinberg S, et al; Genetic Risk and Outcome in Psychosis (GROUP). Common variants conferring risk of schizophrenia. Nature. 2009;460(7256):744-747. DOI: 10.1038/nature08186

Steiner J, Jacobs R, Panteli B, et al. Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity. Eur Arch Psychiatry Clin Neurosci. 2010;260(7):509-518. DOI: 10.1007/s00406-010-0098-x

Wang M, Tsai C, Lin CW, Yeh C, Wang Y, Lin H. Association Between Antipsychotic Agents and Risk of Acute Respiratory Failure in Patients With Chronic Obstructive Pulmonary Disease. JAMA Psychiatry. 2017;74(3):252–260. doi:10.1001/jamapsychiatry.2016.3793 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2595040

Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26 (10):1636-1643. https://www.nature.com/articles/s41591-020-1051-9

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