Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights

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Highlights

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Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
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Some COVID-19 patients have exhibited widespread neurological manifestations including stroke.
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Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19.
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COVID-19-associated coagulopathy is likely caused by inflammation.
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Resultant ACE2 down-regulation causes RAS imbalance, which may lead to stroke.

Abstract

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the pathophysiological stroke mechanisms in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, over-activate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection .

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Most cited references 79

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

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

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 Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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

Dawei Wang, Bo Hu, Fangfang Zhu … (2020)

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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Author and article information

Contributors

Afshin A. Divani

Sasan Andalib

Mario Di Napoli

Simona Lattanzi

M. Shazam Hussain

José Biller

Louise D. McCullough

M. Reza Azarpazhooh

Alina Seletska

Stephan A. Mayer

Michel Torbey

Journal

Journal ID (nlm-ta): J Stroke Cerebrovasc Dis

Journal ID (iso-abbrev): J Stroke Cerebrovasc Dis

Title: Journal of Stroke and Cerebrovascular Diseases

Publisher: Elsevier Inc.

ISSN (Print): 1052-3057

ISSN (Electronic): 1532-8511

Publication date PMC-release: 12 May 2020

Publication date (Electronic): 12 May 2020

Electronic Location Identifier: 104941

Affiliations

[* ]Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA

[† ]Research Unit of Clinical Physiology and Nuclear Medicine, Department of Nuclear Medicine, Odense University Hospital, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

[‡ ]Neuroscience Research Center, Department of Neurosurgery, Poursina Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

[§ ]Department of Neurology and Stroke Unit, San Camillo de' Lellis District General Hospital, Rieti, Italy

[¶ ]Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy

[ǁ ]Cerebrovascular Center, Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA

[** ]Department of Neurology, Loyola University, Stritch School of Medicine, Maywood, IL, USA

[†† ]Department of Neurology, McGovern Medical School, The University of Texas at Houston, Houston, TX, USA

[‡‡ ]Departments of Neurology, Stroke Prevention & Atherosclerosis Research Center Western University, London, Canada

[§§ ]Department of Neurology, Henry Ford Health System, Detroit, MI, United States

Author notes

[1 ]Correspondence to: Afshin A. Divani, Ph.D., University of New Mexico, Department of Neurology, MSC10-5620, 1 University of New Mexico, Albuquerque, NM 87131. adivani@ 123456gmail.com

[a]

Co-first authors contributed equally to the paper.

Article

Publisher ID: S1052-3057(20)30347-5 Publisher ID: 104941

DOI: 10.1016/j.jstrokecerebrovasdis.2020.104941

PMC ID: 7214348

PubMed ID: 32689643

SO-VID: fa4dd537-a076-4c17-bf90-3fe4ee6ecbcd

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights

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Novel Coronavirus Disease COVID-19

Most cited references 79

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

Clinical Characteristics of Coronavirus Disease 2019 in China

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

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