Neuropsychiatric manifestations of long COVID.

Publication date: Oct 01, 2025

In 2019 after the COVID-19 outbreak, a subset of patients was observed to be experiencing unusual symptoms and prolonged illness following SARS-CoV-2 infection and were labeled as “Long-haulers”. Various terms like Long COVID, and Post-COVID-19 Conditions (PCC) were used to describe symptoms extending four weeks or more. Long COVID encompasses a range of persistent symptoms with a multisystemic nature, exhibiting a relapsing-remitting pattern. Various theories explaining Long COVID such as direct neuro-invasion, systemic effects of the virus, and neuroimmune dysregulation have been suggested. Clinical manifestations of Long COVID include diverse symptoms with fatigue, dyspnea, and cognitive impairment being common symptoms reported. Neurological manifestations are more prevalent in severe COVID-19 cases. Non-specific neurological manifestations include loss of taste and smell while specific neurological manifestations include hemiplegia and large artery ischemic stroke. COVID-19 medications may also cause neurological symptoms. Psychiatric manifestations include depression, anxiety, panic disorders, post-traumatic stress disorder (PTSD), psychosis, and cognitive symptoms such as attention and executive function deficits. Psychological symptoms vary among different social groups like frontline health workers, young individuals, and the elderly. Social isolation exerts a substantial impact on the psychological presentations of Long COVID through mechanisms such as Hypothalamic-Pituitary-Adrenal axis (HPA) hyperactivation, epigenetic modifications, increased steroid concentrations, immune system suppression, and reactivation of latent infections. Conclusively, neuroimmune dysregulation, social isolation and associated factors serve as the link between SARS-CoV-2 virus, long COVID and its neuropsychiatric manifestations.

Semantics

Original Article