People with schizophrenia are almost three times more likely to die from the COVID-19


People with schizophrenia, a mental disorder that affects mood and perception of reality, are almost three times more likely to die from the coronavirus than those without the psychiatric illness, a new study shows.

Their higher risk, the investigators say, cannot be explained by other factors that often accompany serious mental health disorders, such as higher rates of heart disease, diabetes, and smoking.

Led by researchers at NYU Grossman School of Medicine, the investigation showed that schizophrenia is by far the biggest risk factor (2.7 times increased odds of dying) after age (being 75 or older increased the odds of dying 35.7 times).

Male sex, heart disease, and race ranked next after schizophrenia in order.

“Our findings illustrate that people with schizophrenia are extremely vulnerable to the effects of COVID-19,” says study lead author Katlyn Nemani, MD.

“With this newfound understanding, health care providers can better prioritize vaccine distribution, testing, and medical care for this group,” adds Nemani, a research assistant professor in the Department of Psychiatry at NYU Langone Health.

The study also showed that people with other mental health problems such as mood or anxiety disorders were not at increased risk of death from coronavirus infection.

Since the beginning of the pandemic, experts have searched for risk factors that make people more likely to succumb to the disease to bolster protective measures and allocate limited resources to people with the greatest need.

Although previous studies have linked psychiatric disorders in general to an increased risk of dying from the virus, the relationship between the coronavirus and schizophrenia specifically has remained unclear. A higher risk of mortality was expected among those with schizophrenia, but not at the magnitude the study found, the researchers say.

The new investigation is publishing Jan. 27 in the journal JAMA Psychiatry. Researchers believed that other issues such as heart disease, depression, and barriers in getting care were behind the low life expectancy seen in schizophrenia patients, who on average die 15 years earlier than those without the disorder.

The results of the new study, however, suggest that there may be something about the biology of schizophrenia itself that is making those who have it more vulnerable to COVID-19 and other viral infections. One likely explanation is an immune system disturbance, possibly tied to the genetics of the disorder, says Nemani.

For the investigation, the research team analyzed 7,348 patient records of men and women treated for COVID-19 at the height of the pandemic in NYU Langone hospitals in New York City and Long Island between March 3 and May 31, 2020. Of these cases, they identified 14 percent who were diagnosed with schizophrenia, mood disorders, or anxiety.

Then, the researchers calculated patient death rates within 45 days of testing positive for the virus.

They note that this large sample of patients who all were infected with the same virus provided a unique opportunity to study the underlying effects of schizophrenia on the body.

“Now that we have a better understanding of the disease, we can more deeply examine what, if any, immune system problems might contribute to the high death rates seen in these patients with schizophrenia,” says study senior author Donald Goff, MD. Goff is the Marvin Stern Professor of Psychiatry at NYU Langone.

Goff, also the director of the Nathan S. Kline Institute for Psychiatric Research at NYU Langone, says the study investigators plan to explore whether medications used to treat schizophrenia, such as antipsychotic drugs, may play a role as well.

He cautions that the study authors could only determine the risk for patients with schizophrenia who had access to testing and medical care. Further research is needed, he says, to clarify how dangerous the virus may be for those who lack these resources. Goff is also the vice chair for research in the Department of Psychiatry at NYU Langone.

COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since its emergence at the end of 2019.1 Various risk factors for severe outcomes of COVID-19 have been elucidated.1, 2 Risk factors are typically conditions that reduce general immunity and are associated with a history of chronic disease.1, 2

These factors include being aged older than 65 years and having pre-existing conditions such as chronic obstructive pulmonary disease and asthma, hypertension, cardiovascular disease, chronic kidney disease, diabetes, obesity, malignancy, use of anti-inflammatory biological agents and transplantation, and chronic infection with HIV.2, 3

Mental illness adversely affects outcomes of various medical conditions.4 People with mental disorders are less likely to undergo screening for medical comorbidities,4, 5 and have a higher mortality and a poorer prognosis when they are diagnosed with a disease than the general population.5

Evidence concerning whether patients with a severe mental illness have different susceptibility to infection with SARS-CoV-2 or clinical outcomes after infection is scarce. Mental health disorders might increase the risk of infection in some individuals due to possible cognitive impairment as a result of the condition, a reduced awareness of risks, and fewer patients being accepted into psychiatric wards.6

Discrimination and stigma associated with mental illness might make it more difficult for individuals at risk to access health services at the appropriate time.7 Public health crises could cause recurrence or exacerbation of an existing mental health condition if individuals have a heightened stress response to the COVID-19 pandemic compared with the general public.8

We showed that people with a previous diagnosis of a mental illness had the same risk for testing positive for SARS-CoV-2 as people with no history of mental illness in a nationwide cohort from South Korea. Patients with a mental illness had slightly worse clinical outcomes of COVID-19 but the numbers were small.

Respiratory diseases such as pneumonia are one of the major causes of death in patients with a severe mental illness.6 A previous study with a large cohort (n=103 997) showed that chronic mental illness is an independent risk factor for mortality in patients with pneumonia.15

In addition, infectious pathogens (eg, toxoplasma, cytomegalovirus, Epstein-Barr virus) chronically induce or aggravate mental illness, including psychiatric disorders, cognitive disorders, personality disorders, and suicidal behaviour.16 These findings imply that mental illness is inherently associated with worse clinical pathophysiology rather than just affecting health screening or transmission of infection.

Mental illness itself is associated with high mortality17 and affects lifestyle, daily habits, socioeconomic status, and prognosis of comorbidity, which could affect the clinical outcomes of COVID-19. Social isolation, fear of infection, job loss, city lockdown, bereavements, and lack of a caregiver or family support could worsen a patient’s underlying mental illness.18, 19, 20

Compared with people without depression, a patient with depression is about three times more likely not to follow treatment recommendations21 and depression is associated with a 1·8 times increased mortality from coronary heart disease.22 Concomitant mood disorder states progressively worsen health with a decreased life-time expectancy compared with depression alone, chronic disease alone, or comorbid chronic medical disease without depression.23

A severe mental illness, including schizophrenia spectrum disorders, bipolar affective disorder, depression with psychosis, other psychotic illness, or first-episode psychosis,24 results in serious functional impairment. Such disorders can cause abnormal thinking and perception, a loss of touch with reality, delusions, or hallucinations leading to cognitive impairment and social isolation, which could result in not seeking care, poor adherence to treatment, and difficulty in obtaining health care.

Patients with a severe mental illness have a worse quality of life than people with disorders such as anxiety and depression.25 We found that patients with a severe pre-existing mental illness were 2·3 times more likely to have severe COVID-19 outcomes than patients with no history of mental illness or other mental illnesses.

More severe COVID-19 outcomes also occurred in the inpatient treatment group compared with the outpatient treatment group. The effect of mental illness severity could be derived from one or a combination of factors such as a reduction in self-care and risk avoidance, isolation from society, and physical health conditions.23, 26

Our results suggest that for patients with COVID-19, their history of mental illness might influence clinical outcomes. Severe mental illness can be considered as a risk factor of severe COVID-19 illness that justifies additional attention and possibly treatment.

For patients with a history of severe mental illness who are infected with SARS-CoV-2, psychiatric and psychological consultation is recommended to assist with his or her self-assertion and communication, the biggest difficulties for managing severe mental illness in the clinic.18 Patients with a severe mental illness showing acute respiratory symptoms should be prioritised for medical care. Active surveillance, monitoring, and support of people at risk for chronic stress disorders, depression, anxiety disorders, psychosis, substance use, and suicide should be put in place.18

Our study has several limitations. First, we defined mental illness on the basis of ICD codes in insurance claims data. However, claims-based definitions of mental illnesses are widely used, and these administrative data have high specificity with variable sensitivity for diagnoses and medical conditions.12, 27

Second, our database does not include medications, which might affect the response to infection with SARS-CoV-2. By activating GABAA receptors in immune cells, benzodiazepines increase susceptibility to infection and double the risk of secondary infections in patients who are critically ill.28 Further study is needed to determine whether the severity of COVID-19 is associated with benzodiazepine use.

Third, our analysis did not adjust for possible confounding factors such as obesity and cigarette smoking, although we included history of cardiovascular disease, diabetes, and respiratory disease, which are associated with these factors.29 We could not match patient education level, socioeconomic status, and household income. Diagnosis and treatment of COVID-19 were provided free-of-charge by the South Korean Government; however, socioeconomic factors could still affect outcomes. Fourth, the COVID-19-related data provided by the government included only 3·5 years of the patient’s psychiatric history, whereas a previous study found 7 years to be necessary to identify the incidence of schizophrenia in public health plan databases.30

In conclusion, using a large, nationwide, propensity score matched cohort, we found no evidence of a relationship between SARS-CoV-2 test positivity and mental illness, but possible evidence of an association between mental illness and the severity of COVID-19 clinical outcomes. More research is needed to support our findings and to investigate further the relationship between mental illness and COVID-19. Meanwhile, clinicians should record the history of mental illness in patients with COVID-19 and take it into consideration for prognosis and care.


Original Research: Closed access.
Association of Psychiatric Disorders With Mortality Among Patients With COVID-19” by Katlyn Nemani et al. JAMA Psychiatry


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