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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Caused the 2019 Coronavirus Disease (COVID-19) which claimed more than 5.25 million lives worldwide and continues to claim over 200,000 deaths per month. The wide range of clinical manifestations of COVID-19 is still only partially understood. Recent studies report that a large proportion of COVID-19 patients develop neuropsychiatric symptoms during or after acute infection.
To study: Increased risk of psychiatric sequelae from COVID-19 highest early in clinical course. Image Credit: Elizaveta Galitckaia / Shutterstock
Current evidence suggests an increased risk of mental illness as a result of viral infections, although there is no definitive evidence for this. A detailed understanding of molecular mechanisms is also lacking. Coronavirus were previously known to cause outbreaks of Severe Acute Respiratory Syndrome (SARS) in 2002 and Middle East Respiratory Syndromes (MERS) in 2012; incidentally, these two offending coronaviruses are closely linked to SARS-CoV-2. They were also associated with neurological manifestations in some cases. Several studies have also found evidence of an increased risk of mental illness after infection with SARS-CoV-2.
Understanding the risk of long-term psychiatric manifestations following COVID-19 is crucial, as even a small increase in risk would have major ramifications for public health. A cohort study of 44,779 COVID-19 patients and propensity-score-matched controls from the TriNetX network found a statistically significant increase in new mental illnesses 14 to 90 days after diagnosis of COVID-19 compared to healthy controls. This finding was then extended to a larger cohort of 236,379 COVID-19 patients. An observation period of up to 6 months was encountered with comparable results.
Researchers recently published a report in medRxiv* in which they confirmed the aforementioned findings of an increased risk for 46,610 COVID-19 survivors of developing mental illness within 120 days of acute infection.
Study details
In this retrospective cohort study, researchers looked at the incidence of new-onset mental illness in recovering COVID-19 patients and compared them to control patients with a similar health event. They used patient data provided by the N3C accessible through the National Institute of Health (NIH) N3C data enclave. The N3C has harmonized the EHRs of 65 clinical organizations in the United States. Fourteen sites were deleted due to missing BMI data. The files for the remaining 51 sites were finalized on October 20, 2021.
The final data set included information from 7,139,696 patients, of which 1,834,913 were positive for COVID-19. Data was available for more than 4.6 billion lab results, 1.4 billion drug exposures, and 469 million procedures for 467 million physician visits.
Patients were included in the primary analysis if they had a confirmed COVID-19 diagnosis proven by polymerase chain reaction (PCR) or antigen test after January 1, 2020. Patients with suspected COVID-19 who had not undergone confirmatory testing were excluded from this study.
Control patients were not limited by the initial presentation date. Patients with a history of mental illness before 21 days after being diagnosed with COVID-19 and patients without a medical record going back one year before COVID-19 were also excluded from this study.
The final analysis was conducted with data from 2,965,506 COVID-19 positive patients and compared COVID-19 patient cohorts with comparable controls. Patients were matched by propensity score to control for confounding factors. The researchers estimated the risk ratio (COVID-19: control) for the onset of mental illness in the first year after diagnosis. They further estimated the change in risk of recent onset mental illness between the periods of 21-120 and 121-365 days after infection.
Researchers found a significant increase (3.8%) in the incidence of new-onset mental disorders during the 21-120 day period following COVID-19 (95% CI: 3.6-4 , 0) compared with 3% in patients with respiratory tract infections (95% CI: 2.8-3.2). They further showed that the risk of new-onset mental illness was reduced in the first year after being diagnosed with COVID-19 compared to other respiratory tract infections. They demonstrated a reduced risk ratio (not significant) over the period of 121-365 days after diagnosis. Similar results were seen for newly-onset anxiety disorders, but not for mood disorders.
Implications
It was concluded that patients who recovered from COVID-19 had an increased risk of developing new-onset mental illness, especially anxiety disorders. This risk was greatest during the first 120 days after infection.
Such studies are useful in determining the course of management of post-illness sequelae in COVID-19 patients. Special measures should be taken when caring for vulnerable patients, especially the elderly. These studies also help highlight the increased need to view mental health as a serious outcome of COVID-19, on par with any physical or behavioral abnormalities, and reach out to these patients with equal sincerity.
*Important Notice
medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.
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