Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants
Simone Beretta, Viviana Cristillo, Giorgia Camera, Carlo Morotti Colleoni, Gaia Pellitteri, Beatrice Viti, Elisa Bianchi, Stefano Gipponi, Maria Grazia Grimoldi, Mariarosaria Valente, Susanna Guttmann, Maria Sofia Cotelli, Pasquale Palumbo, Giorgio Gelosa, Stefano Meletti, Cristina Schenone, Donatella Ottaviani, Massimo Filippi, Andrea Zini, Paola Basilico, Lucia Tancredi, Pietro Cortelli, M. Braga, Valeria De Giuli, Serenella Servidei, Damiano Paolicelli, Federico Verde, Stefano Caproni, Antonio Pisani, Vincenzina Lo Re, Luca Massacesi, Daria Roccatagliata, Paolo Manganotti, Daniele Spitaleri, Anna Maria Formenti, Marta Piccioli, Lidia Marino, Paola Polverino, Umberto Aguglia, Raffaele Ornello, Elisabetta Perego, Gabriele Siciliano, Paola Merlo, Marco Capobianco, Leonardo Pantoni, Alessandra Lugaresi, Stefania Angelocola, Anna De Rosa, Maria Sessa, Ettore Beghi, Elio Clemente Agostoni, Salvatore Monaco, Alessandro Padovani, Alberto Priori, Vincenzo Silani, Gioacchino Tedeschi, Carlo Ferrarese, for Neuro-COVID Italy, for Neuro-COVID Italy, Andrea Pilotto, Stefano Cotti Piccinelli, Susanna Lazzari, G Negro, Giulia Sofia Cereda, R Infante, Ginevra Giovannelli, Claudia Cutellé, Lorenzo Tinti, Susanna Diamanti, Gaia Fanella, Nicola Rifino, Lucio Tremolizzo, Giovanni Ermanis, Fedra Kuris, Roberto Sartor, Francesco Bax, Gian Luigi Gigli, Edoardo Barvas, Mirco Volpini, Roberto Frusciante, Mariaeva Bernardi, Marinella Turla, Raffaella Valenti, Raffaella Valenti, Lorenzo Kiferle, Silvia Pradella, Alessandro Innocenti, Ludovico Ciolli, Niccolò Orlandi, Gabriele Vandelli, Marco Mazzoli, Luana Benedetti, Matteo Pardini, Stefano Grisanti, Erica Biassoni, Corrado Cabona, Angelo Schenone, Federica Boso, Federica Agosta, Mario Orrico
Abstract
<h3>Background and Objective</h3> A variety of neurological disorders has been reported as presentations or complications of COVID-19 infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. <h3>Methods</h3> The Neuro-COVID Italy study was a multicentre, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurological disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020 to June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms or death. <h3>Results</h3> Among 52759 hospitalized COVID patients, 1865 patients presenting 2881 new neurological disorders associated with COVID-19 infection (neuro-COVID) were recruited. Incidence of neuro-COVID cases significantly declined over time, comparing the first three pandemic waves (8.4%, 95% CI [7.9, 8.9]; 5.0%, 95% CI [4.7, 5.3]; 3.3%, 95% CI [3.0, 3.6], respectively; p = 0.027). The most frequent neurological disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%) and cognitive impairment (13.7%). The onset of neurological disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by the majority of neuro-COVID patients (64.6%) during follow-up (median 6.7 months) and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI [0.05, 0.50]; p = 0.019). Mild residual symptoms were frequently reported (28.1%), while disabling symptoms were common only in stroke survivors (47.6%). <h3>Discussion</h3> Incidence of COVID-associated neurologic disorders decreased during the pre-vaccination phase of the pandemic. Long-term functional outcome was favourable in most neuro-COVID disorders, although mild symptoms commonly lasted over 6 months after infection.