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      COVID-19 and cerebrovascular diseases: a comprehensive overview

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          Abstract

          Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as ‘red flags’ to alarm clinicians in recognizing COVID-19-related stroke.

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          Most cited references146

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          Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

          Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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            Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

            The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.
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              Incidence of thrombotic complications in critically ill ICU patients with COVID-19

              Introduction COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. Methods We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. Results We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. Conclusion The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.
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                Author and article information

                Contributors
                Journal
                Ther Adv Neurol Disord
                Ther Adv Neurol Disord
                TAN
                sptan
                Therapeutic Advances in Neurological Disorders
                SAGE Publications (Sage UK: London, England )
                1756-2856
                1756-2864
                8 December 2020
                2020
                : 13
                : 1756286420978004
                Affiliations
                [1-1756286420978004]Second Department of Neurology, School of Medicine, National & Kapodistrian University of Athens, Rimini 1, Chaidari, Athens 12462, Greece
                [2-1756286420978004]Department of Neurology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
                [3-1756286420978004]Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, ‘Attikon’ University Hospital, Athens, Greece
                [4-1756286420978004]Department of Neurology, Neuroscience Institute, Geisinger Health System, Danville, Pennsylvania, USA
                [5-1756286420978004]Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
                [6-1756286420978004]Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany
                [7-1756286420978004]Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, ‘Attikon’ University Hospital, Athens, Greece
                [8-1756286420978004]Division of Neurology, McMaster University/Population Health Research Institute, Hamilton, ON, Canada
                [9-1756286420978004]Division of Neurology, McMaster University/Population Health Research Institute, Hamilton, ON, Canada
                [10-1756286420978004]Division of Neurology, Department of Medicine, YLL School of Medicine, National University of Singapore, Singapore
                [11-1756286420978004]Department of Neurology, Neuroscience Institute, Geisinger Health System, Danville, Pennsylvania, USA
                [12-1756286420978004]Stroke Unit and Neurosonology Laboratory, Padua University Hospital, Padua, Italy
                [13-1756286420978004]First Department of Cardiology, Hippokration Hospital, University of Athens, Athens, Greece
                [14-1756286420978004]Second Department of Psychiatry, National and Kapodistrian University of Athens, School of Medicine, ‘Attikon’ University Hospital, Athens, Greece
                [15-1756286420978004]First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
                [16-1756286420978004]Department of Neurology, Stroke Unit, Oslo University Hospital, Oslo, Norway
                [17-1756286420978004]Department of Neurology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
                [18-1756286420978004]Fourth Department of Internal Medicine, ‘Attikon’ University Hospital, National and Kapodistrian University of Athens, Athens, Greece
                Author notes
                Author information
                https://orcid.org/0000-0002-0640-3797
                https://orcid.org/0000-0001-7757-609X
                https://orcid.org/0000-0002-9477-0094
                https://orcid.org/0000-0002-8976-5696
                https://orcid.org/0000-0001-8871-1023
                Article
                10.1177_1756286420978004
                10.1177/1756286420978004
                7727052
                33343709
                c5319f1d-07d3-43e3-b94c-370a8675ac1e
                © The Author(s), 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 27 September 2020
                : 11 November 2020
                Categories
                Review
                Custom metadata
                January-December 2020
                ts1

                cerebrovascular disease,covid-19,sars-cov-2,stroke
                cerebrovascular disease, covid-19, sars-cov-2, stroke

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