Mechanisms of Stroke in COVID-19

Spence, J. David; Freitas, Gabriel R. de; Pettigrew, L. Creed; Ay, Hakan; Liebeskind, David S; Kase, Carlos S.; Brutto, Oscar H. Del; Hankey, Graeme J.; Venketasubramanian, Narayanaswamy

doi:10.1159/000509581

Cited by 197 publications

(259 citation statements)

References 59 publications

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“…. These findings from the comparison between strokes with and without COVID-19 could suggest that some mechanisms directly related to COVID-19 have a role in the occurrence of stroke, and explain the characteristic profile of stroke in infected patients.Large artery occlusion in COVID-19 may be primarily due to cardioembolism or paradoxical embolism, and less often due to large artery atherosclerosis and plaque rupture(31), thus explaining the occurrence of stroke among young people without vascular risk factors, in individuals with high levels of D-dimer or other signs of hypercoagulability, or in patients with pulmonary embolism and venous thrombosis(19).An important question is whether stroke occurring in individuals with COVID-19 is causally related, or represents an incidental association due to COVID-19 infection being widespread in the occurrence of stroke in those with COVID-19 does not provide direct evidence of causality between the two diseases. As with all observational studies, residual confounding may be an explanation, as a substantial proportion of the patients hospitalized with COVID-19 and stroke exhibit several vascular risk factors; also, some COVID-19-related factors, such as less controlled vascular risk factors and mental stress, may also contribute to stroke.…”

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confidence: 99%

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

Nannoni

Groot

Bell

et al. 2020

International Journal of Stroke

475

496

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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 (CVD) 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 CVD in COVID-19 (December 2019-September 2020). The review protocol was previously registered (PROSPERO ID=CRD42020185476). Data were extracted from articles reporting ï³5 stroke cases in COVID-19. We complied with the PRISMA guidelines, and used the NewcastleâOttawa Scale to assess data quality. Data were pooled using a random-effects model. Summary of review: Of 2,277 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 haemorrhage was less common (11.6%). Patients with COVID-19 developing acute CVD, 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 CVD is not uncommon in 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 suggest that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

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confidence: 99%

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

Nannoni

Groot

Bell

et al. 2020

International Journal of Stroke

475

496

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“…The strokes are frequently labeled as cryptogenic, but diagnostic investigations could not be completed in some COVID-19 patients and that may contribute to this high rate. Different mechanisms of stroke appear to be directly related to COVID-19 and are being progressively reported [ 4 ]. This includes a hypercoagulable state possibly linked to the viral invasion of the vascular endothelium, which may trigger activation of the complement system leading to thrombotic and inflammatory cascades [ 3 , 4 ].…”

Section: Discussionmentioning

confidence: 99%

Acutely altered mental status as the main clinical presentation of multiple strokes in critically ill patients with COVID-19

et al. 2020

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Background and aims Cerebral infarction in COVID-19 patients might be associated with a hypercoagulable state related to a systemic inflammatory response. Its diagnosis might be challenging. We present two critically ill patients with COVID-19 who presented acutely altered mental status as the main manifestation of multiple strokes. Methods Clinical presentation and diagnostic work-up of the patients. Results Two patients in their sixties were hospitalized with a bilateral pneumonia COVID-19. They developed respiratory failure and were admitted to ICU for mechanical ventilation and intense medical treatment. They were started on low-molecular-weight heparin since admission. Their laboratory results showed lymphopenia and increased levels of C-reactive protein and D-dimer. Case 1 developed hypofibrinogenemia and presented several cutaneous lesions with biopsy features of thrombotic vasculopathy. Case 2 was performed a CT pulmonary angiogram at ICU showing a bilateral pulmonary embolism. When waking up, both patients were conscious but with a remarkable global altered mental status without focal neurological deficits. A brain MRI revealed multiple acute bilateral ischemic lesions with areas of hemorrhagic transformation in both patients (case 1: affecting the left frontal and temporal lobes and both occipital lobes; case 2: affecting both frontal and left occipital lobes). Cardioembolic source and acquired antiphospholipid syndrome were ruled out. COVID-19-associated coagulopathy was suspected as the possible main etiology of the strokes. Conclusion Acutely altered mental status might be the main manifestation of multiple brain infarctions in critically ill COVID-19 patients. It should be specially considered in those with suspected COVID-19-associated coagulopathy. Full-dose anticoagulation and clinical-radiological monitoring might reduce their neurological consequences.

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“…Recently, three main mechanisms, including hypercoagulopathy, vasculitis and cardiomyopathy leading to stroke in COVID-19 patients, have been described, while the role of various vascular and immune-mediated factors in the pathogenesis of stroke in these patients remain unclear [ 7 ]. Our first and second patient showed significant arterial lesions, while the third patient showed a high burden of cerebral venous sinus thrombosis with raised D-dimers and inflammatory markers, leading to stroke.…”

Section: Discussionmentioning

confidence: 99%

“…Our first patient showed an extensive thrombus in an atypical location emanating from the common carotid artery to the terminal right ICA and the second patient revealed a significant localized intracranial lesion. It remains unclear whether such large lesions are formed at the site or are embolic in nature [ 7 ]. As there is no other explanation for such lesions in our previously healthy and young patients, we hypothesize that SARS-CoV-2 possibly led to significant local inflammation and thrombus formation.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Related Cerebrovascular Thromboembolic Complications in Three Young Patients

et al. 2020

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Coronavirus disease 2019 (COVID-19) is a viral illness, caused by the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). It is currently affecting millions of people worldwide and is associated with coagulopathy, both in the venous and arterial systems. The proposed mechanism being excessive inflammation, platelet activation, endothelial dysfunction, and stasis. As an ongoing pandemic declared by WHO in March 2020, health systems worldwide are experiencing significant challenges with COVID-19-related complications. It has been noticed that patients with COVID-19 are at greater risk of thrombosis.

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Mechanisms of Stroke in COVID-19

Cited by 197 publications

References 59 publications

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

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

Acutely altered mental status as the main clinical presentation of multiple strokes in critically ill patients with COVID-19

COVID-19 Related Cerebrovascular Thromboembolic Complications in Three Young Patients

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