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Up to 3 years after being hospitalized with acute SARS-CoV-2 during the first months of the pandemic, some patients still had mild to severe cognitive and psychiatric outcomes, data from the COVID Fog (C-Fog) study showed.

At the 2- to 3-year point, a group of early COVID survivors scored significantly lower than expected across all cognitive domains, showing an average deficit equivalent to 10 IQ points (average score 0.71 standard deviations below the mean, P<0.0001), reported Maxime Taquet, PhD, of the University of Oxford in England, and co-authors in .

One in nine had objective signs of severe cognitive deficits that equated to a difference of 30 IQ points.

At 2 to 3 years, most participants reported at least mild anxiety (74.5%), fatigue (53.5%), or subjective cognitive decline (52.1%). More than a fifth said these symptoms were severe. Symptoms at 2 to 3 years were not predicted by the severity of acute COVID-19, but by the degree of recovery at 6 months.

More than a quarter of participants (26.9%) changed occupations after having COVID, with poor health being the most common reason. Occupation changes were associated with cognitive deficits.

"The findings show that problems affecting attention and memory -- as well as fatigue, depression, and anxiety -- continue to afflict some people even 3 years after COVID-19 infection, especially those who had not recovered well by 6 months," co-author Paul Harrison, FRCPsych, also of the University of Oxford, told MedPage Today.

"These results apply only to people who needed acute hospital admission when they had COVID-19," Harrison emphasized. "We suspect, but do not know, whether similar kinds of problems might affect the much larger number of people who did not get hospitalized."

C-Fog was a study nested within the study of hospitalized U.K. COVID patients. Of 2,469 PHOSP-COVID patients invited to participate in the C-Fog study, 475 provided data at the 2- to 3-year follow-up. All had SARS-CoV-2 infection before the Delta variant emerged.

C-Fog is one of few studies to prospectively follow early hospitalized COVID patients. Its findings add to data showing higher rates of cognitive decline and dementia among older patients hospitalized with COVID-19, noted Tracy Vannorsdall, PhD, of Johns Hopkins Medicine in Baltimore, and co-authors in an .

"The observation of cognitive decline 2-3 years after infection among hospitalized patients in this study of relatively young COVID-19 survivors (mean age 58.3 years) is particularly concerning," Vannorsdall and colleagues wrote.

"The primary study finding -- that the degree of symptom improvement achieved within the first 6 months after illness predicts later neuropsychiatric dysfunction -- suggests a window of opportunity for positively altering the trajectory of patient outcomes," they added.

Prior studies showed that 10.7% of hospitalized patients discharged after severe SARS-CoV-2 infection in Brazil had long-term impairment that persisted for 1 year. Among COVID-19 survivors discharged from Wuhan hospitals in early 2020, the incidence of cognitive impairment 12 months later was 12.45%.

The C-Fog study included mostly men (59.8%) with a mean age of 58 who were discharged with a COVID diagnosis between Feb. 1, 2020, and March 31, 2021.

In this group, depression, anxiety, and fatigue were worse at 2 to 3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms, Taquet and colleagues reported.

The degree of recovery at 6 months explained 35% to 49% of the variance in anxiety, depression, fatigue, and subjective cognitive decline symptoms at 2 to 3 years. A profile linking elevated D-dimer relative to C-reactive protein during acute COVID with subjective cognitive deficits at 6 months also explained 7% to 17% of the variance at 2 to 3 years.

Objective cognitive deficits at 2 to 3 years were not predicted by any factor tested except cognitive deficits at 6 months, which explained about 11% of their variance.

Occupation changes were linked with both objective cognitive deficits (OR 1.51, 95% CI 1.04-2.22 for every standard deviation decrease in overall cognitive score) and subjective cognitive decline (OR 1.54, 95% 1.21-1.98 for every point increase on the 20-item Cognitive Change Index questionnaire).

The findings were limited to patients hospitalized with COVID early in the pandemic and may not apply to those infected with later variants or who were vaccinated. The low response rate and high symptom prevalence suggest that selection bias may have occurred.

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