D. Plantone, D. Righi, C. Manco, N. De Stefano
University of Siena,
Italy
Keywords: biomarkers, neurology, COVID-19, neurofilaments, glial fibrillary acidic protein
Summary:
In recent years, biomarkers have emerged as invaluable tools in neurology, offering insights into the pathophysiology, diagnosis, and prognosis of neurological disorders. Beyond primary neurologic diseases, biomarkers play a crucial role in understanding neurological complications associated with systemic illnesses, including infections. The recent COVID-19 pandemic has highlighted the importance of investigating these neurological implications, both during the acute phase of the infection and in the post-recovery period. Our past and current research at the Centre for Translational and Precision Medicine at the University of Siena aims to explore the utility of serum biomarkers in neurological and non-neurological diseases. We recently assessed the role of biomarkers for COVID-19 patients, focusing on neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), markers of neuronal and glial degeneration, respectively. In a first single-center prospective study, we assessed sNfL and sGFAP levels in 148 hospitalised COVID-19 patients without clinical neurological symptoms, comparing them to patients with interstitial pulmonary fibrosis (IPF) and healthy controls (HCs). Our findings revealed significantly elevated levels of sNfL and sGFAP in COVID-19 patients, compared to IPF and HCs suggesting neuroaxonal damage and astrocytic activation secondary to the viral infection. Furthermore, we developed a prognostic model incorporating sNfL, sGFAP, and age, which demonstrated predictive value for in-hospital COVID-19-associated mortality. In addition to this acute phase assessment in hospitalised patients with no neurological manifestations, we recently performed a second study in a group of 147 adult patients with a previous asymptomatic SARS-CoV2 infection or mild COVID-19, one week and, in 49 of them, ten months after SARS-Cov2 negativisation and compared them to a group of 82 age and BMI‐matched healthy controls. At the first assessment, sNfL and sGFAP levels were significantly higher in COVID-19 patients than in HCs. The eleven COVID-19 patients with cognitive impairment had significantly higher levels of sNfL and sGFAP than the others. At the subsequent follow-up, sNfL and sGFAP levels showed a significant decrease, although they were still higher than HCs. These results suggest ongoing damage involving neurons and astrocytes after SARS-Cov2 negativization, which reduces after ten months even if still evident compared to HCs. Our research demonstrates the valuable role of these serum biomarkers in exploring the subclinical neurological involvement associated with systemic illnesses such as COVID-19. Furthermore, our findings suggest that these biomarkers hold promise in predicting disease severity and prognosis, thereby guiding clinical management and risk stratification. Overall, our work underscores the importance of investigating serum biomarkers in understanding the neurological implications of systemic illnesses, providing insights that extend beyond COVID-19. We are currently leveraging homebrew technology integrated with Simoa assay platforms to enhance the specificity of biomarker detection such as the seven human neurofilament isoforms, to have a better distinction between central and peripheral neuronal damage. Through ongoing research efforts, we aim to identify novel biomarkers that can provide insights into the pathophysiology of neurological complications associated with COVID-19 and other systemic illnesses.