The association of post-COVID-19 fatigue in the acute phase with neuropsychiatric and neurocognitive symptoms trajectory over time and long-term health-related quality of life among Chinese adults.

Abstract

Background: Post-viral fatigue is a common and debilitating neurological sequela of COVID-19, often accompanied with multidimensional neuropsychiatric symptoms (post-viral fatigue, sleep disturbance, anxiety, depression, and post-traumatic stress disorder) and neurocognitive impairment. We sought to characterize the trajectory of these neurological symptoms and investigate the relationship between acute-phase fatigue (< 1 month) and the chronicity of neuropsychiatric and neurocognitive symptoms, as well as long-term health-related quality of life (HRQoL) at 3 months post-infection.

Methods: A prospective, multi-center, longitudinal study was conducted from January to February 2023 within a cohort of individuals with a mild SARS-COV-2 infection and contemporaneous healthy controls (HCs). Comprehensive neuropsychiatric and neurocognitive assessments were collected for COVID-19 survivors during both acute and chronic phase post-infection, with the EQ-5D-5L (a standardized instrument for assessing HRQoL) evaluated at the chronic phase. Healthy controls underwent the same protocol for recruitment to the study. Linear mixed models were used to access the impact of acute-phase fatigue on different neuropsychiatric and neurocognitive scales over time.

Results: Three hundred thirty-five COVID-19 survivors and 79 HCs were included in the study. COVID-19 survivors exhibited poorer performance in various neuropsychiatric domains during the acute phase, with the exception of cognitive impairment. A significant amelioration of emotional symptoms, including anxiety and depression, was observed from the acute to chronic phase among COVID-19 survivors, reaching levels comparable to those of HCs. However, at 3 months post-infection, survivors continued to report higher levels of fatigue and poorer sleep quality compared to HCs, although the differences had diminished from the acute phase. The impact of the pandemic event persisted, and no significant changes in cognitive performance were observed. Acute-phase fatigue was associated with poorer sleep and worse emotional problems during the recovery process (from the acute to the chronic phase), and further exacerbated overall HRQoL at 3 months post-infection (EQ index score, p = 0.001, Cohen's d = -0.33; EQ-VAS, p = 0.007, Cohen's d = -0.19).

Conclusions: Our findings provide novel evidence on the distinct temporal trajectories for post-acute COVID-19 sequelae in a longitudinal study, highlighting the negative impact of acute-phase fatigue on the process of neuropsychiatric recovery and long-term HRQoL.