; for the CORIMUNO-19 Collaborative Group IMPORTANCE Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). OBJECTIVE To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. DESIGN, SETTING, AND PARTICPANTS This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. INTERVENTIONS Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. MAIN OUTCOMES AND MEASURES Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. RESULTS Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care...

is the seventh member of the family of coronaviruses that infect humans (1) and induces coronavirus disease 2019 (COVID-19). Human coronaviruses have neuroinvasive capacities and may be neurovirulent by two main mechanisms (2-4): viral replication into glial or neuronal cells of the brain or autoimmune reaction with a misdirected host immune response (5). Thus, a few cases of acute encephalitislike syndromes with human coronaviruses were reported in the past 2 decades (5-8). In regard to COVID-19, current data on central nervous system involvement are uncommon but growing (9-17), demonstrating the high frequency of neurologic symptoms. However, the delineation of a large cohort of confirmed brain MRI parenchymal signal abnormalities (excluding ischemic infarcts) related to COVID-19 has never been performed, and the underlying pathophysiologic mechanisms remain unknown. The purpose of the current study was to describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe COVID-19 and report the clinicobiologic profile of these patients. Materials and Methods This retrospective observational national multicenter study was initiated by the French Society of Neuroradiology in collaboration with neurologists, intensivists, and infectious disease specialists and brought together 16 hospitals. The study was approved by the ethical committee of Strasbourg University Hospital (CE-2020-37) and was in accordance with the 1964 Helsinki Declaration and its later amendments. Because of the emergency in the context of the COVID-19 pandemic responsible for

ObjectiveTo describe neuroimaging findings and to report the epidemiological and clinical characteristics of COVID-19 patients with neurological manifestations.MethodsIn this retrospective multicenter study (10 Hospitals), we included 64 confirmed COVID-19 patients with neurologic manifestations who underwent a brain MRI.ResultsThe cohort included 43 men (67%), 21 women (33%), and the median age was 66 years (range: 20-92). 36 (56%) brain MRIs were considered abnormal, possibly related to SARS-CoV-2. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurological manifestation, following by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from the other patients with abnormal brain imaging since the former had less frequently acute respiratory distress syndrome (p=0·006) and more frequently corticospinal tract signs (p=0·02). Patients with encephalitis were younger (p=0·007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p=0·009).ConclusionsCOVID-19 patients may develop a wide range of neurological symptoms, which can be associated with severe and fatal complications, such as ischemic stroke or encephalitis. Concerning the meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology rather seems to involve an immune and/or inflammatory process given the presence of signs of inflammation in both cerebrospinal fluid and neuroimaging but the lack of virus in cerebrospinal fluid.

. This first systematic literature review confirms the rarity of IM and may highlight certain genetic and environmental determinants of IM. There is a need for uniformity in diagnostic and classification criteria as well as more exhaustive case ascertainment to refine IM epidemiology.