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Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected
Simone Beretta1, Viviana Cristillo2, Giorgia Camera2
1From the Department of Neurology (S.B., C.M.C., C.F.), Fondazione IRCCS San Gerardo dei Tintori, Monza; Department of Medicine and Surgery (S.B., C.M.C., C.F.), University of Milano Bicocca; The Milan Center for Neuroscience (NeuroMI) (S.B., G.G., C.F.); Neurology Unit and Department of Clinical and Experimental Sciences (V.C., S. Gipponi, A. Padovani), University of Brescia; Unit of Neurology and Neurophysiology (G.C., M.G., M.S.), ASST PG23, Bergamo; Santa Maria della Misericordia University Hospital (G.P., M.V.), Udine, Italy; San Marino Neurological Unit (B.V., S. Guttmann), San Marino Hospital; The Mario Negri Institute for Pharmacological Research IRCCS (E. Bianchi, E. Beghi), Milan; Department of Medical Area (DAME) (M.V.), University of Udine; Neurology Unit (M.S.C.), ASST Valcamonica, Esine, Brescia; USL Centro Toscana (P. Palumbo), Neurology Unit, Nuovo Ospedale Santo Stefano, Prato; Department of Neurology and Stroke Unit (G.G., E.C.A.), Niguarda, Milan; Department of Neurology and Department of Clinical Neurophysiology AOU Modena (S. Meletti), University of Modena and Reggio Emilia; Department of Neuroscience, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health (C.S.), University of Genoa; Ospedale Santa Maria del Carmine di Rovereto (D.O.), Trento; Neurology Unit (M.F.), IRCCS San Raffaele Scientific Institute, Milan; Department of Neurology (A.Z.), Metropolitan Stroke Network, Ospedale Maggiore, Bologna; Department of Neurology (P.B.), Ospedale A. Manzoni ASST Lecco; University of Milan (L.T., L.P., A. Priori); Neurology Unit (L.T., A. Priori), ASST Santi Paolo e Carlo; Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics (L.T.), Milan; IRCCS Institute of Neurological Science of Bologna (P.C.); DIBINEM (P.C.), University of Bologna; UOC Neurology (M.B.), ASST Vimercate; Department of Neurology (V.D.G.), ASST Cremona; Neurophysiopathology Unit, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy; Department of Basic Medical Sciences, Neurosciences and Sense Organs (D.P.), University of Bari; Department of Neurology and Laboratory of Neuroscience (F.V., V.S.), IRCCS Istituto Auxologico Italiano; "Dino Ferrari" Center (F.V., V.S.), Department of Pathophysiology and Transplantation, Università degli Studi di Milano; Neurology Division (S.C.), "S. Maria" University Hospital, Terni; IRCCS Mondino Foundation (A. Pisani), Department of Brain and Behavioral Sciences, University of Pavia; Department of Diagnostic and Therapeutic Services (V.L.R.), IRCCS ISMETT, Palermo; Department of Neurology 2 (L.M.), Careggi University Hospital, Florence; Department of Neurology and Neurosurgery (D.V.R.), ASST di Mantova; Clinical Neurology Unit (P. Manganotti), Cattinara University Hospital, University of Trieste; Department of Neurology (D.L.A.S.), AORN S.Giovanni Moscati, Avellino; Neurology and Stroke Unit (A.F.), Neuroscience Department, ASST-Lecco, Merate; Department of Neurology (M.P.), Ospedale San Filippo Neri, Rome; IRCCS Centro Neurolesi Bonino-Pulejo (S. Marino), Messina; Department of Neurology (P. Polverino), IRCCS Humanitas Research Hospital, Rozzano, Milan; Department of Medical and Surgical Sciences (U.A.), Magna Graecia University of Catanzaro; Department of Biotechnological and Clinical Sciences (R.O.), University of L'Aquila; Department of Neurology (E.P.), Ospedale Valduce, Como; Neurological Clinic (G.S.), University of Pisa; Department of Neurology (P. Merlo), Humanitas Gavazzeni, Bergamo; Department of Neurology (M.C.), S. Luigi Gonzaga Hospital, Orbassano; Ospedale Luigi Sacco (L.P.), Milan; IRCCS Institute of Neurological Science of Bologna (A.L.), UOSI Multiple Sclerosis Rehabilitation; Department of Biomedical Science and Neuromotricity (A.L.), University of Bologna; Department of Neurology (S.A.), Fermo; Department of Neurosciences (A.D.R.), Federico II University, Naples; Neurology Unit and Department of Neurosciences (S. Monaco), University of Verona; IRCCS Fondazione Ospedale Maggiore Policlinico (A. Priori), Milan; and Department of Advanced Medical and Surgical Sciences (G.T.), University of Campania, Naples, Italy. simone.beretta@unimib.it.
Background And Objectives:
A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome.
Methods:
The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic 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-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death.
Results:
Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 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 neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic 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 most patients with neuro-COVID (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%).
Discussion:
Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.
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