key: cord-0740162-7vhcsaw1
authors: de Oliveira, Roberta Marina Ferreira; de Souza Aguiar, Pedro Henrique Chaves; de Paula, Raphael Wellerson Rodrigues Mayrink; Simões, Carlos Eduardo Nardouto; Almeida, Lucas Garrido; Barceló, Alberto; Galil, Arise Garcia de Siqueira
title: Stroke in patients infected by the novel coronavirus and its causal mechanisms: A narrative review
date: 2020-12-26
journal: J Am Coll Emerg Physicians Open
DOI: 10.1002/emp2.12332
sha: ade994770bf4707108acb604f3ca1be57daf48a8
doc_id: 740162
cord_uid: 7vhcsaw1

OBJECTIVE: The current study aimed to evaluate the mechanisms of stroke development during the coronavirus disease 2019 (COVID‐19) pandemic and analyze the related characteristics, such as etiology, age group, associated comorbidities, and prognosis. METHODS: A narrative was performed using the descriptors [“novel coronavirus”] AND [“stroke”] in the PubMed, Science Direct, Google Scholar, Lilacs, and Biblioteca Virtual em Saúde (BVS) databases, including studies published between December 1, 2019, and April 28, 2020. RESULTS: A total of 142 articles were identified, with 89 of them in the PubMed database, 46 in Science Direct, and 7 in Google Scholar. No articles were found using the defined keywords in the Lilacs and BVS databases. A total of 22 articles were included for final evaluation. We observed that infection by the novel coronavirus caused a greater risk of the occurrence of stroke, with several studies suggesting etiological mechanisms, such as the involvement of angiotensin‐converting enzyme 2, viral invasion, and hypoxia as well as the increase in D‐dimer and the reduction in platelets, which had been commonly observed in COVID‐19 cases. The most common complication of stroke was found among the elderly with preexisting comorbidities, mainly cardiovascular disease. We detected reports of strokes among young people with no preexisting risk factors for thromboembolic events, in which the mechanism related to the viral infection was the most probable cause. In this review, we confirmed that stroke is part of the spectrum of clinical manifestations resulting from COVID‐19 and is associated with a worse prognosis. Cerebrovascular lesions resulting from complications of the infection by the novel coronavirus occurred as a result of ischemic, hemorrhagic, and/or thromboembolic etiologies. CONCLUSION: The occurrence of stroke during the pandemic as a result of the novel coronavirus has a multifactorial character, and emergency physicians should focus on systematic measures for its screening and accurate diagnosis as well as on appropriate interventions based on early decisionmaking that may have a favorable impact on reducing damage and saving lives.

complications of the infection by the novel coronavirus occurred as a result of ischemic, hemorrhagic, and/or thromboembolic etiologies.

The occurrence of stroke during the pandemic as a result of the novel coronavirus has a multifactorial character, and emergency physicians should focus on systematic measures for its screening and accurate diagnosis as well as on appropriate interventions based on early decisionmaking that may have a favorable impact on reducing damage and saving lives. Regarding the neurological symptoms in patients with COVID-19, they usually manifest mildly and include headache, dizziness, and neuralgia.

Other cases can be more severe, with neurological complications such as stroke. 5 Stroke has an ischemic etiology in 80% of cases, while the minority has a hemorrhagic cause. 6 Stroke is a medical emergency with an increasing incidence, and it is the second leading cause of death worldwide. 7 whereas the rate in the general population without COVID-19 is 0.5%.

In addition to respiratory symptoms, the perception of neurological symptoms also should be considered as an indicator for the diagnosis of patients with COVID-19. 5 In most cases, stroke first occurs in the emergency sectors, in which the early identification of suspected cases is a priority as well as the appropriate decisionmaking, with significant impacts on the morbidity and mortality of these patients. 10 Given the possibility of the association between COVID-19 and stroke, two lethal clinical conditions, it is important for health profes-sionals, particularly those working in acute care settings, to understand and focus on the clinical picture and pathophysiology of these diseases to save as many lives as possible. Therefore, the objective of the present review was to summarize the literature to date on ischemic stroke and COVID-19, evaluating the mechanisms of stroke development during COVID-19.

We conducted a narrative review of studies on the novel coronavirus that contained information on associated stroke. The objectives were based on the population, intervention, comparisons, and outcomes strategy and choice of descriptors. 11 

For the proposed review, 142 articles were identified: 89 articles in tomography images, and significantly higher mortality. These data were reinforced in recent studies in which the elderly and patients with cardiovascular disease showed a higher prevalence of acute stroke as a complication of COVID-19. [23] [24] [25] [26] In addition to these lines of evidence, the disease severity was also associated with hypercoagulability, as indicated by the high concentration of D-dimers. 27 Giannis et al 28 showed that the stroke mechanism in these patients with different profiles does not appear to be similar. Figure 1 shows the probable pathophysiological mechanisms involving COVID-19 and the occurrence of neurological symptoms and stroke.

As a limitation of the study, no detailed description was provided for other neurological conditions that did not coincide with stroke as well as for post-COVID-19 neurological manifestations. Although we recognize their importance, it was not the priority objective of this review.

The This finding could explain peripheral neuronal manifestations, such as the loss of smell and taste, present in those infected by the novel coronavirus. 5 The virus could also explore a pathway mediated by both macrophages and the lymphatic pathways to reach the brain as well as other organs. 5 Another possible related mechanism is the persis- thy that could lead to venous and arterial thromboembolic events. 23, 32 In cases of hemorrhagic events, the suggested cause was the theory of the involvement of SARS-CoV-2 and ACE2 expressed in the capillary endothelium. This interaction could result in arterial hypertension and, consequently, an increased risk of cerebral hemorrhage. 1, 13, 15, 17, 18 The coagulation cascade could also be present due to the prothrombotic responses caused by the virus, resulting in the formation of blood clots. 31 Thus, in the infected population, there is unification of the inflammatory pathways and coagulation in the genesis of thromboembolic complications, possibly by activation of factors that compound the Virchow triad, including vascular damage, altered blood flow, and blood hypercoagulability. 33 Thus, 2 key points were highlighted for the assessment and decision making by professionals in the acute care settings regarding those infected with the novel coronavirus who also show stroke manifestations. The first is the attention to the manifestations of stroke in patients with risk factors or preexisting diseases in which stroke could occur as a result of a decompensation of underlying diseases. The second is regarding previously healthy patients in whom the direct action of the virus would contribute both to the cytokine storm and a greater occurrence of thromboembolic events. 5, 21 The strengths of the present review include highlighting the strong emerging evidence for the importance of tracking neurological symptoms, as already performed for respiratory symptoms, in patients infected with the novel coronavirus. In the emergency department,

where these patients usually have their first attendance, this screening should be performed early and systematically because once the diagnosis of neurological symptoms is confirmed in co-occurrence or as a complication of the viral disease, it will course with greater severity, with a higher prevalence of hospitalization in intensive care and higher mortality.

In this review, we confirmed that stroke is part of the spectrum of clinical manifestations resulting from COVID-19 and is associated with a worse prognosis. Cerebrovascular lesions resulting from complications of the infection by the novel coronavirus occurred as a result of ischemic, hemorrhagic, and/or thromboembolic etiologies. Thus, the occurrence of stroke during the pandemic due to the novel coronavirus has a multifactorial character, and emergency physicians should focus on systematic measures for its screening and accurate diagnosis as well as the appropriate interventions based on early decisionmaking, which may have a favorable impact on reducing damage and saving lives.

All authors declare that they have no financial relationships with any organization that may have an interest in the work submitted in the previous 3 years and no other relationship or activity that may appear to have influenced the work submitted.

All data used to prepare this article are available from the sources cited.

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