Two-year trajectory of cognitive decline and neurological sequelae in COVID-19 survivors with acute neurological symptoms

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Introduction The COVID-19 pandemic caused by SARS-CoV-2 has profound implications for global public health. It significantly affects the nervous system and cognitive function. The emergence of long COVID has raised concerns regarding long-term cognitive impairment, particularly among patients who experienced neurological symptoms during the acute phase of infection. Aim This study investigated the impact of neurological symptoms during acute SARS-CoV-2 infection on subsequent cognitive change and neurological sequelae over a 2-year period. Methods We enrolled 3,419 hospitalized patients with confirmed infection in Wuhan, China (Dec 2022–Mar 2023), and 2,087 completed follow-ups. Propensity score matching identified 901 patients with acute neurological symptoms and 901 controls. Cognitive decline was measured with the Informant Questionnaire on Cognitive Decline in the Elderly, and cognitive status with the Telephone Interview of Cognitive Status-40. Multivariable regression was used to examine risk factors and cognitive changes, and residual neurological symptoms and new-onset symptoms were also analyzed. Results Acute neurological symptoms, particularly central nervous system manifestations such as delirium and brain fog, were strongly associated with both cognitive decline (aOR, 2.16; 95% CI, 1.53–3.07) and cognitive impairment (aOR, 2.75; 95% CI, 1.73–4.49). Delirium, brain fog, stroke, numbness, and facial paralysis were associated risk factors (all p < 0.05). After 2 years’ follow-up, most acute neurological symptoms had subsided, yet fatigue (8.66%) and brain fog (5.99%) persisted. Comorbidities did not significantly increase the risk of persistent symptoms. For the new-onset symptoms, the proportion of insomnia, tinnitus, blurred vision, movement disorder, palpitation, muscle weakness, and respiratory symptoms were much higher in the neurological symptom group ( p < 0.05), with a highest proportion in insomnia (9.99% vs. 5.22%, p < 0.001), compared with the non-neurological symptom group. Conclusion Acute neurological symptoms, especially central nervous system manifestations, were strongly associated with long-term cognitive decline and new-onset symptoms (mainly insomnia) in COVID-19 survivors. This study uniquely reveals the persistence of high levels in brain fog and fatigue at 2-year’s follow up, despite overall subsidence of most acute manifestations, underscoring the need for early intervention and sustained monitoring in this high-risk population.

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