COVID-19 Hospitalization Survivors Report Worse Long-Term Cognition


Case-control analyses suggest older patients may cognitively age by about 8 years within 6 months of being discharged for severe COVID-19.

COVID-19 Hospitalization Survivors Report Worse Long-Term Cognition

Daniel Kondziella, MD

Survivors of COVID-19 hospitalization are reporting worsened cognitive status at 6 months, while neuropsychiatric and neurologic symptoms and signs of burden are similar to that observed by patients to survive hospitalization for other conditions.

In a new prospective, case-control analysis from a tertiary referral hospital in Copenhagen, investigators reported that about 1 in 5 patients previously hospitalized with COVID-19 were diagnosed with a new-onset psychiatric condition at 6 months—a rate similar to that observed among other patients hospitalized with non-COVID issues.

Even more concerning, scores per Montreal Cognitive Assessment (MoCA) were worse among COVID-19 hospitalization survivors at 6 months than among control patients. The findings may be the first case-control assessment of neuropsychiatric and cognitive outcomes in patients to survive severe forms of the pandemic virus.

Led by Daniel Kondziella, MD, and Michael E. Benros, MD, PhD, of the Copenhagen University Hospital, investigators sought to interpret the rate of cognitive and neuropsychiatric burden and symptoms in survivors of COVID-19 compared to patients hospitalized for other conditions. Previous research has shown depression, anxiety, mental fatigue, sleep disturbance, and even posttraumatic stress disorder (PTSD) can occur frequently among patients considered to suffer from “long COVID.”

“Several disease mechanisms play a role in the development of neuropsychiatric illness during and after COVID-19, including infectious and immunologic causes, critical illness, and the social consequences of lockdown measures,” investigators wrote. “However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions.”

The team sought to establish relevant patient scores from MoCA, the Mini-International Neuropsychiatric Interview, a neurologic examination, and a clinician interview for subjective patient symptoms. The primary outcomes were total MoCA score and new onset psychiatric diagnoses per ICD-10. Secondary outcomes included specific psychiatric diagnoses, subjective symptoms, and neurologic examination results.

Investigators adjusted outcomes for patient age, sex, intensive care unit (ICU) admission, hospitalization length, and days of follow-up. Patients were excluded if they lacked Danish or English language proficiency, suffered a severe central nervous system injury during admission, had dementia, active psychosis, or previous COVID-19 diagnosis.

The final study included 85 COVID-19 survivors assessed after hospitalization and 61 matched control patients with non-COVID illness. Mean COVID-19 patient age was 59.4 years old, and 44% of patients were women.

Cognitive state per total geometric mean MoCA scores were lower among COVID-19 survivors at 6 months (26.7; 95% CI, 26.2 – 27.1) than control patients (27.5; 95% CI, 27.0 – 27.9). However, cognitive status was improved from hospital discharge (19.2; 95% CI, 15.2 – 23.2) to 6 months (26.1; 95% CI, 23.1 – 29.1) among the 15 COVID-19 patients assessed at both periods.

Investigators observed new-onset psychiatric diagnoses in 16 of 85 (19%) patients with COVID-19 at 6 months, versus 12 of 61 (20%) control patients (OR, 0.93; 95% CI, 0.39 – 2.27; P = .87). They did not observe significantly different secondary outcomes among the patient arms, aside for anosmia being more common among COVID-19 patients (OR, 4.56; 95% CI, 1.52 – 17.42; P = .006).

Though the 0.8 percentage-point difference in MoCA scores among patients with and without COVID-19 at 6 months may appear insignificant, investigators stressed results from a recent population sample that would show this difference is equivalent to cognitively aging by 8 years for people in their 60s. “Given the pandemic, this might translate to considerable cognitive impairment on a global scale,” they wrote.

The team concluded that cognitive impairment was indeed more severe among hospitalized COVID-19 survivors, though neurologic and neuropsychiatric symptoms and diagnoses were similar with that observed in other hospitalized patients.

“Further studies with larger samples are needed to investigate if smaller differences in neuropsychiatric profiles exist,” they wrote.

The study, “Neuropsychiatric and Cognitive Outcomes in Patients 6 Months After COVID-19 Requiring Hospitalization Compared With Matched Control Patients Hospitalized for Non–COVID-19 Illness,” was published online in JAMA Psychiatry.

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