Objective This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID‐19) in people with multiple sclerosis (PwMS). Methods We retrospectively collected data of PwMS with suspected or confirmed COVID‐19. All the patients had complete follow‐up to death or recovery. Severe COVID‐19 was defined by a 3‐level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID‐19 by multivariate and propensity score (PS)‐weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID‐19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty‐eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti‐CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID‐19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20–12.53, p = 0.001). Results were confirmed by the PS‐weighted analysis and by all the sensitivity analyses. Interpretation This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID‐19 pandemic persists. ANN NEUROL 2021;89:780–789

We evaluated the effect of DMTs on Covid‐19 severity in patients with MS, with a pooled‐analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid‐19 severity was assessed by multivariate ordinal‐logistic models and pooled by a fixed‐effect meta‐analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti‐CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid‐19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled‐analysis confirms an increased risk of severe Covid‐19 in patients on anti‐CD20 therapies and supports the protective role of interferon.

Several hospital-based studies suggest a circadian rhythm for stroke, with a peak of onset in the morning. To verify whether these results could be confirmed in a community-based study, we used data from the SEPIVAC, a community-based stroke register in Umbria, Italy. Cerebral infarctions (48%), primary intracerebral hemorrhages (54%), subarachnoid hemorrhages (53%) and ''not known'' strokes (51%) were all more common between 6 a.m. and noon, and this peak was still present when strokes recognized on awakening were evenly redistributed over the sleep period. Looking at the subgroups of cerebral infarction, lacunar syndromes were more common during sleep. Cerebral infarctions were more frequent during winter, and primary intracerebral hemorrhages during autumn.

The SEPIVAC study is a communitybased epidemiological survey of incidence and outcome of acute cerebrovascular disease in the Sixth Local Health Unit, Umbria, Italy (population 49 218). The study was carried out from 1 September 1986 to 31 August 1989. There were 375 patients who were registered with a first ever stroke, with a crude rate of 2-54 (95% confidence limits 2-29-2-81) per 1000 per year; the rate adjusted to the European population is 1 55 (CL 1-36-1-77). The age adjusted relative risk for males is 1-35 (CL 1-101-66). Up to 15% of the patients were not admitted to hospital during the acute phase of their disease. At least 286 (76-3%, CL 72-80 6) of the cases were due to cerebral ischaemia; in 56 of these (19-6%, CL 15-24-2) a clinical diagnosis of lacunar ischaemia was made. The 30 day case fatality rate was 20-3% (CL 16-2-24-3); between one and six months 7-5% (CL 5-10-6) of patients died.

Background: Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit.

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