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      Stroke in COVID-19: A systematic review and meta-analysis

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          Abstract

          Background

          Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear.

          Aims

          We aimed to characterize the incidence, risk factors, clinical–radiological manifestations, and outcome of COVID-19-associated stroke.

          Methods

          Three medical databases were systematically reviewed for published articles on acute cerebrovascular diseases in COVID-19 (December 2019–September 2020). The review protocol was previously registered (PROSPERO ID = CRD42020185476). Data were extracted from articles reporting ≥5 stroke cases in COVID-19. We complied with the PRISMA guidelines and used the Newcastle–Ottawa Scale to assess data quality. Data were pooled using a random-effect model.

          Summary of review

          Of 2277 initially identified articles, 61 (2.7%) were entered in the meta-analysis. Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0–1.9). The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%). Patients with COVID-19 developing acute cerebrovascular diseases, compared to those who did not, were older (pooled median difference = 4.8 years; 95%CI: 1.7–22.4), more likely to have hypertension (OR = 7.35; 95%CI: 1.94–27.87), diabetes mellitus (OR = 5.56; 95%CI: 3.34–9.24), coronary artery disease (OR = 3.12; 95%CI: 1.61–6.02), and severe infection (OR = 5.10; 95%CI: 2.72–9.54). Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference = −6.0 years; 95%CI: −12.3 to −1.4), had higher NIHSS (pooled median difference = 5; 95%CI: 3–9), higher frequency of large vessel occlusion (OR = 2.73; 95%CI: 1.63–4.57), and higher in-hospital mortality rate (OR = 5.21; 95%CI: 3.43–7.90).

          Conclusions

          Acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors. The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

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          Most cited references53

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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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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              A pneumonia outbreak associated with a new coronavirus of probable bat origin

              Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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                Author and article information

                Journal
                Int J Stroke
                Int J Stroke
                WSO
                spwso
                International Journal of Stroke
                SAGE Publications (Sage UK: London, England )
                1747-4930
                1747-4949
                11 November 2020
                February 2021
                : 16
                : 2
                : 137-149
                Affiliations
                [1 ]Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, UK
                [2 ]Donor Medicine Research, Sanquin Research, Amsterdam, the Netherlands
                Author notes
                [*]Stefania Nannoni, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK. Email: sn572@ 123456medschl.cam.ac.uk
                Author information
                https://orcid.org/0000-0002-1825-1874
                Article
                10.1177_1747493020972922
                10.1177/1747493020972922
                7859578
                33103610
                48495d6d-852d-46b4-ba87-70a9faa53a8c
                © 2020 World Stroke Organization

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

                History
                : 28 September 2020
                : 20 October 2020
                Categories
                Review
                Custom metadata
                ts2

                Cardiovascular Medicine
                stroke,covid-19,sars-cov-2,acute cerebrovascular disease,hemorrhagic stroke

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