Neuropsychiatric Symptoms After COVID-19 Hospitalization No More Frequent Than After Other Hospitalizations

Neuropsychiatric symptoms and disorders, including fatigue, anxiety, memory complaints, dementia, and psychotic disorders, may persist after acute COVID-19 illness, according to very large claims-based studies and other research.

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After carefully deriving an appropriate comparator group, Massachusetts General Hospital researchers determined that although neuropsychiatric post-acute sequelae of COVID-19 are common and may warrant treatment, they are not specific to COVID-19. In fact, rates of some symptoms were substantially lower in post–COVID-19 patients. Victor M. Castro, MS, a data scientist at Mass General Brigham, Roy Perlis, MD, MSc, director of the Center for Quantitative Health in the Department of Psychiatry at Mass General, and colleagues report the findings in Molecular Psychiatry.

Methods

This study differed from most prior research on the issue in that the controls were individuals hospitalized at the same time as the case patients with COVID-19. The researchers adjusted for sociodemographic and clinical features rather than matching diagnoses similar to COVID-19.

Patients were included in the study if they:

• Were 18 to 99 years old
• Were admitted emergently to any of six Eastern Massachusetts hospitals between March 1, 2020, and May 15, 2021 (excluding labor and delivery and elective admissions)
• Had a documented PCR test result for COVID-19 (positive or negative)
• Were discharged alive within 30 days of test positivity

6,619 of the hospitalized patients tested positive for COVID-19 and 36,342 did not.

Another difference from previous work is that the research team captured symptoms, not just diagnostic codes (symptoms may be present even if unassociated with a formal diagnosis). Specifically, the team relied on natural language processing, which uses a computer algorithm to filter through the narrative portion of electronic health records and identify relevant words and phrases.

Results

31 to 90 days after COVID-19 testing:

• In unadjusted models—Cognitive symptoms, fatigue, and hallucinations were significantly more frequent among patients with prior COVID-19 than among COVID-19–negative patients
• In models adjusted for sociodemographic features and hospital course (e.g., hospital type, ICU admission, mechanical ventilation)—Certain neuropsychiatric symptoms were less common in post–COVID-19 patients: headache (adjusted OR, 0.84), language disturbance (aOR, 0.42), and mood and anxiety symptoms (aOR, 0.72)

91 to 150 days after COVID-19 testing:

• In unadjusted models—The most common neuropsychiatric symptoms in post–COVID-19 patients were fatigue (10.9%), mood and anxiety symptoms (8.2%), sleep disruption (6.8%), headache (6.1%), and impaired cognition (5.8%); rates in COVID-19–negative patients were similar
• In adjusted models—Symptom frequencies remained similar in post–COVID-19 patients and COVID-19–negative patients, except mood and anxiety symptoms were less common among post–COVID-19 patients (aOR, 0.63)

The Path Forward

The finding that post–COVID-19 neuropsychiatric symptoms are not specific to COVID-19 in no way detracts from the need to develop rehabilitative strategies for them. Indeed, this study highlights the need to develop a broad range of interventions for persistent cognitive and psychiatric symptoms, regardless of etiology.

Moreover, the neuropsychiatric consequences of COVID-19 undoubtedly persist for a subset of individuals. They have a great capacity to diminish the quality of life and warrant further investigation.

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