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      SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy

      research-article
      1 , , 2 , 3 , 1 , 4 , 5 , 6 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 1 , 1 , 14 , 3 , 1 , 1 , 1 , 1 , 1 , 7 , 7 , 8 , 9 , 2 , 4 , 3 , 3 , 4 , 4 , 15 , 5 , 6 , 5 , 6 , 15 , 15 , 15 , 10 , 11 , 12 , 16 , 4 , 4 , 5 , 6 , 3 , 14 , 1 , the STROKOVID group
      Journal of Neurology
      Springer Berlin Heidelberg
      Stroke, Risk factors, COVID-19, Viral infection

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          Abstract

          Objective

          To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients.

          Methods

          In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19.

          Results

          Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06–2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05–2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17–5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death.

          Conclusions

          Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00415-021-10620-8.

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          Most cited references36

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          Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

          In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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            Extrapulmonary manifestations of COVID-19

            Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
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              COVID-19 and its implications for thrombosis and anticoagulation

              Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC). The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness. The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. COVID-19–associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC. Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated. Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported. If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.
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                Author and article information

                Contributors
                ale_pezzini@hotmail.com
                Journal
                J Neurol
                J Neurol
                Journal of Neurology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5354
                1432-1459
                24 May 2021
                24 May 2021
                : 1-11
                Affiliations
                [1 ]GRID grid.7637.5, ISNI 0000000417571846, Department of Clinical and Experimental Sciences, , University of Brescia, ; P.le Spedali Civili, 1, 25123 Brescia, Italy
                [2 ]GRID grid.8982.b, ISNI 0000 0004 1762 5736, Department of Brain and Behavioural Sciences, Statistics and Genomic Unit, , University of Pavia, ; Pavia, Italy
                [3 ]GRID grid.413174.4, ISNI 0000 0004 0493 6690, Department of Neurology and Stroke Unit, , Carlo Poma Hospital, ASST Mantova, ; Mantova, Italy
                [4 ]GRID grid.419450.d, Neurology Unit, Istituti Ospitalieri, , ASST Cremona, ; Cremona, Italy
                [5 ]GRID grid.415025.7, ISNI 0000 0004 1756 8604, Department of Neurology, , Ospedale San Gerardo, ASST Monza, ; Monza, Italy
                [6 ]GRID grid.7563.7, ISNI 0000 0001 2174 1754, Department of Medicine and Surgery and Milan Center for Neuroscience, , University of Milano-Bicocca, ; Milan, Italy
                [7 ]GRID grid.412725.7, Vascular Neurology-Stroke Unit, , Spedali Civili Hospital, ASST Spedali Civili, ; Brescia, Italy
                [8 ]Neurology Unit, Ospedale Nuovo, ASST Ovest Milanese, Legnano, Italy
                [9 ]Neurology Unit and Stroke Unit, Department of Neurosciences and Niguarda Neuro Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
                [10 ]GRID grid.412972.b, Neurology Unit, Ospedale di Circolo e Fondazione Macchi, , ASST Sette Laghi, ; Varese, Italy
                [11 ]GRID grid.413175.5, ISNI 0000 0004 0493 6789, Neurology Unit, Ospedale “A. Manzoni”, , ASST Lecco, ; Lecco, Italy
                [12 ]GRID grid.417728.f, ISNI 0000 0004 1756 8807, Emergency Neurology and Stroke Unit, , IRCCS Humanitas Clinical and Research Center, ; Rozzano, Milan, Italy
                [13 ]GRID grid.460094.f, ISNI 0000 0004 1757 8431, Department of Neuroradiology, , Papa Giovanni XXIII Hospital, ASST Papa Giovanni XXIII, ; Bergamo, Italy
                [14 ]GRID grid.460094.f, ISNI 0000 0004 1757 8431, Department of Neurology, , Papa Giovanni XXIII Hospital, ASST Papa Giovanni XXIII, ; Bergamo, Italy
                [15 ]GRID grid.416317.6, ISNI 0000 0000 8897 2840, Neurology Unit, Ospedale “Sant’Anna”, , ASST Lariana, ; Como, Italy
                [16 ]Stroke Unit, IRCCS Fondazione “C. Mondino”, Pavia, Italy
                Author information
                http://orcid.org/0000-0001-8629-3315
                Article
                10620
                10.1007/s00415-021-10620-8
                8142879
                34031747
                3a1c5160-8ba3-40ad-b270-c1c3bf947c15
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 27 January 2021
                : 5 May 2021
                : 18 May 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100009882, Regione Lombardia;
                Award ID: STROKOVID
                Funded by: Università degli Studi di Brescia
                Categories
                Original Communication

                Neurology
                stroke,risk factors,covid-19,viral infection
                Neurology
                stroke, risk factors, covid-19, viral infection

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