A recent The Lancet Psychiatry study investigated whether psychiatric and cognitive symptoms commence or persist beyond a year of coronavirus disease 2019 (COVID-19)-related hospitalization. They investigated early aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that predict long-term symptoms and relationships between the symptoms and occupational functioning.

Background

COVID-19 increases the risk of psychiatric and cognitive outcomes, such as anxiety, depression, and cognitive deficits in hospitalized individuals. The scarcity of long-term longitudinal data makes it unclear whether neuropsychiatric disorders commence or persist beyond the first year, whether acute COVID-19 aspects predict later outcomes, and whether symptoms affect occupational functioning. Electronic health records cannot distinguish between emergent disorders and delayed diagnosis. Studies determining the trajectories of emergent or persistent symptoms and assessing cognitive deficits are limited.

About the study

In the present prospective cohort, longitudinal study, researchers assessed psychiatric, cognitive, and fatigue symptom emergence and evolution over time to identify aspects of acute COVID-19 that predict these outcomes and assess symptom correlation with occupational changes.

The Post-hospitalization COVID-19 (PHOSP-COVID) study included adults hospitalized due to SARS-CoV-2 infection at either of the National Health Service (NHS) hospitals in the United Kingdom. In a subset study, COVID-19 (C-Fog) individuals, followed for three years after hospitalization, completed digital cognitive evaluations and clinical assessment scales two to three years after hospitalization.

Participants completed Cognitron battery tasks spanning eight cognition domains. The domains were immediate and delayed object memory, two-dimensional mental manipulation, simple reaction speed, cognition control, spatial planning, spatial working memory, and verbal analogies. Participants also completed the Patient Health Questionnaire (PHQ9) assessing depression, the seven-item Generalized Anxiety Disorder (GAD7) scale for anxiety, the Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F) Scale, the Cognitive Change Index (CCI-20), and the Patient Symptom Questionnaire (C-PSQ) to evaluate subjective cognitive decay.

The researchers evaluated the risks of symptom evolution at follow-ups of six months, one year, and two to three years post-hospitalization and whether acute COVID-19 aspects predicted symptoms at two to three years. Participants completed occupation change questionnaires to assess occupation or work status changes, reasons for the same, and associated symptoms at two to three years. 

The researchers conducted the assessments between November 23, 2022, and May 1, 2023. They used multivariate linear regressions to derive the odds ratios (OR) for analysis, adjusting for age, sex, and time since hospitalization. They analyzed five factors to predict fatigue, psychiatric, and cognitive outcomes two to three years post-COVID-19, including acute severity markers, psychiatric or neurological comorbidity history, recovery clusters, clinical scales, and two biocognitive profiles. They applied Benjamini-Hochberg corrections across outcomes.

Results

The study included 2,469 PHOSP-COVID individuals for the COVID Fog research, and 475 individuals (60% were male with a mean age of 58 years) receiving hospital discharge provided follow-up data at two to three years. Participants showed worse cognition than expected based on sociodemographic variables across all cognition domains. Out of 353 individuals, most reported mild-moderate fatigue (62%), anxiety (54%), depression (75%), and subjective cognition decline (52%), and above one-fifth experienced severe depression (22%), subjective cognition decline (25%), or fatigue (25%).

Fatigue, anxiety, and depression worsened at two to three years more than at six months or one year, with symptom emergence and worsening. Acute SARS-CoV-2 infection severity did not predict symptoms at two to three years; however, recovery at six months strongly did (explaining 35% to 49% of variances in fatigue, depression, anxiety, and subjective cognition decline) by bio-cognitive profiles relating acutely elevated D-dimer levels about C-reactive proteins (CRP) with subjective cognition deficits at 0.5 years (contributing to 7.0% to 17% of variances in fatigue, depression, anxiety, and subjective cognition decay) and by fatigue, depression, anxiety, and subjective cognition deficits at six months.

Cognition deficits at six months predicted objective cognition deficits at two to three years, explaining 11% of variances. Among 353 individuals, 95 (27%) reported occupational changes, primarily due to poor health. Occupation changes showed robust and specific associations with objective cognition deficits (OR, 1.5 per standard deviation reduction in overall cognition scores) and subjective cognition decay (OR, 1.5 per point elevated CCI-20 score).

Conclusion

The study found that cognitive and psychiatric symptoms increased in the first two to three years following COVID-19 hospitalization, owing to increasing symptom incidence and worsening of prevalent symptoms at six months. Early detection and treatment of symptoms may avoid symptom emergence later. Occupation transitions are widespread, and they are associated with both subjective and objective cognitive losses. Interventions promoting cognition recovery or preventing degradation are required to alleviate COVID-19’s economic and functional constraints.