Insights into long COVID: clinical feature, radiological and functional sequelae, vaccination status, role of neurofilament light chain and glial fibrillary acidic protein as biomarkers of central nervous system damage in long COVID

Long COVID has yet to be comprehensively described. The aim of the study was to describe persistent COVID-19 symptoms in a cohort of hospitalized and home-isolated patients, evaluating the impact of vaccination and the role of brain injury biomarkers (NfL and GFAP) to measure CNS damage. A retrospective cohort study was conducted on long COVID patients. Patients were examined by a multidisciplinary medical team. Blood tests, chest computed tomography (CT), and physical and infectious examinations were performed. Finally, in-patients were evaluated at 2 time-points: on hospital admission (T0) and 3 months after discharge (Tpost). The most commonly reported symptom was fatigue. Chest Computed Tomography (chest CT) scans showed abnormalities in two-thirds of patients, and lung function abnormalities were observed in half of the patients. Women were found to be at higher risk of presenting with at least one symptom, and hospitalized patients were at higher risk of presenting with residual lesions on chest CT scans. In addition, older patients were found to be at greater risk of lung function abnormalities. Vaccination has reduced hospitalization, respiratory support and cardiopulmonary function abnormalities, as well as reducing permanent lung parenchymal damage. However, no association was found between vaccination status and the development of at least one long COVID symptom. Higher plasma levels of NfL and GFAP in COVID-19 patients compared to HD were observed (p < 0.0001, p < 0.0001 respectively), especially in those with severe COVID-19 (p < 0.0001, p < 0.0001 respectively). Patients with neurological symptoms showed higher plasma levels of NfL and GFAP compared to those without (p = 0.0023, p < 0.0001 respectively). At Tpost, the longitudinal evaluation showed a significant reduction in plasma levels of NfL and GFAP compared to baseline (p < 0.0001, p < 0.0001 respectively). Despite vaccination, a significant number of patients experience long-term sequelae, posing a new challenge for the healthcare system. Multidisciplinary teams are essential for developing preventive measures and clinical management strategies for long COVID. Elevated plasma levels of NfL and GFAP suggest substantial central nervous system (CNS) involvement, potentially resulting from a systemic pro-inflammatory response and blood-brain barrier disruption, even when SARS-CoV-2 RNA is not detected in the cerebrospinal fluid or blood.