Biomarkers of Neurological Damage: From Acute Stage to Post-Acute Sequelae of COVID-19
Maria Antonella Zingaropoli,
Patrizia Pasculli,
Christian Barbato,
Carla Petrella,
Marco Fiore,
Federica Dominelli,
Tiziana Latronico,
Federica Ciccone,
Michele Antonacci,
Grazia Maria Liuzzi,
Giuseppina Talarico,
Giuseppe Bruno,
Gioacchino Galardo,
Francesco Pugliese,
Miriam Lichtner,
Claudio Maria Mastroianni,
Antonio Minni,
Maria Rosa Ciardi
Affiliations
Maria Antonella Zingaropoli
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Patrizia Pasculli
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Christian Barbato
Department of Sense Organs, Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Sapienza University of Rome, 00185 Rome, Italy
Carla Petrella
Department of Sense Organs, Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Sapienza University of Rome, 00185 Rome, Italy
Marco Fiore
Department of Sense Organs, Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Sapienza University of Rome, 00185 Rome, Italy
Federica Dominelli
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Tiziana Latronico
Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70121 Bari, Italy
Federica Ciccone
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Michele Antonacci
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Grazia Maria Liuzzi
Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70121 Bari, Italy
Giuseppina Talarico
Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy
Giuseppe Bruno
Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy
Gioacchino Galardo
Medical Emergency Unit, Sapienza University of Rome, Policlinico Umberto I, 00161 Rome, Italy
Francesco Pugliese
Department of Specialist Surgery and Organ Transplantation “Paride Stefanini”, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy
Miriam Lichtner
Infectious Diseases Unit, SM Goretti Hospital, Sapienza University of Rome, 00185 Latina, Italy
Claudio Maria Mastroianni
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Antonio Minni
Department of Sensory Organs, Sapienza University of Rome, 00185 Rome, Italy
Maria Rosa Ciardi
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Background: Neurological symptoms (NS) in COVID-19 are related to both acute stage and long-COVID. We explored levels of brain injury biomarkers (NfL and GFAP) and myeloid activation marker (sCD163) and their implications on the CNS. Materials and Methods: In hospitalized COVID-19 patients plasma samples were collected at two time points: on hospital admission (baseline) and three months after hospital discharge (Tpost). Patients were stratified according to COVID-19 severity based on acute respiratory distress syndrome (ARDS) onset (severe and non-severe groups). A further stratification according to the presence of NS (with and without groups) at baseline (requiring a puncture lumbar for diagnostic purposes) and according to NS self-referred at Tpost was performed. Finally, cerebrospinal fluid (CSF) samples were collected from patients with NS present at baseline. Results: We enrolled 144 COVID-19 patients (62 female/82 male; median age [interquartile range, IQR]): 64 [55–77]) and 53 heathy donors (HD, 30 female/23 male; median age [IQR]: 64 [59–69]). At baseline, higher plasma levels of NfL, GFAP and sCD163 in COVID-19 patients compared to HD were observed (p p p p p p p = 0.0023, p p = 0.0017) and GFAP were observed (ρ = 0.7036, p = 0.0045). At Tpost, the longitudinal evaluation performed on 77 COVID-19 patients showed a significant reduction in plasma levels of NfL, GFAP and sCD163 compared to baseline (p p p = 0.0413, respectively). Finally, at Tpost, in the severe group, higher plasma levels of sCD163 in patients with NS compared to those without were reported (p Conclusions: High plasma levels of NfL, GFAP and sCD163 could be due to a proinflammatory systemic and brain response involving microglial activation and subsequent CNS damage. Our data highlight the association between myeloid activation and CNS perturbations.
