Acute Ischemic and Hemorrhagic Stroke in COVID-19: Mounting Evidence

Abstract

The novel coronavirus disease of 2019 (COVID-19) is caused by the binding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to angiotensin-converting enzyme 2 (ACE2) receptors present on various locations such as the pulmonary alveolar epithelium and vascular endothelium. In COVID-19 patients, the interaction of SARS-CoV-2 with these receptors in the cerebral blood vessels has been attributed to stroke. Although the incidence of acute ischemic stroke is relatively low, ranging from 1% to 6%, the mortality associated with it is substantially high, reaching as high as 38%. This case series describes three distinct yet similar scenarios of COVID-19 positive patients with several underlying comorbidities, wherein two of the patients presented to our hospital with sudden onset right-sided weakness, later diagnosed with ischemic stroke, and one patient who developed an acute intracerebral hemorrhage during his hospital stay. The patients were diagnosed with acute stroke as a complication of COVID-19 infection. We also provide an insight into the possible mechanisms responsible for the lifethreatening complication. Physicians should have a low threshold for suspecting stroke in COVID-19 patients, and close observation should be kept on such patients particularly those with clinical evidence of traditional risk factors.

A case-based systematic review on the SARS-COVID-2-associated cerebrovascular diseases and the possible virus routes of entry

“…The remaining 71 articles (127 patients) that satisfied the criteria mentioned above were included in this review. In this review, 80 cases of patients developed IS during COVID-19 infection (Aasfara et al 2021 ; Abdulkadir et al 2020 ; Agarwal et al 2020 ; Al-Mufti et al 2021 ; Al Saiegh et al 2020 ; Appavu et al 2021 ; Ashraf and Sajed 2020 ; Avula et al 2020 ; Bessa et al 2020 ; Bigliardi et al 2020 ; Burkert and Patil 2020 ; Co et al 2020 ; Dakay et al 2020a , b ; de Almeida Lima et al 2020 ; de Lorenzo Alvarez et al 2021 ; Deliwala et al 2020 ; Dumitrascu et al 2020 ; Efendizade et al 2020 ; El Nahas et al 2020 ; Elshereye and Erdinc 2020 ; Eskandarani et al 2021 ; Fu et al 2021 ; Garg et al, 2020 ; Gemcioglu et al 2020 ; Goette et al 2020 ; Goldberg et al 2020 ; Guillan et al 2020 ; Iqbal et al 2021 ; Kwon et al 2020 ; Mahboob et al 2020 ; Mansour et al 2020 ; Mirzaee et al 2020 ; Morassi et al 2020 ; Mowla et al 2020 ; Patel et al 2020a , b ; Patel et al 2020a , b ; Prasad et al 2021 ; Priftis et al 2020 ; Rajdev et al 2020 ; Rascón-Ramírez et al 2020 ; Roy et al 2021 ; Valderrama et al 2020 ; Viguier et al 2020 ; Zhai et al 2020 ), 32 cases developed intracranial hemorrhage (Ahmad et al 2021 ; Al-Mufti et al 2021 ; Al Saiegh et al 2020 ; Carroll and Lewis 2021 ; Cezar-Junior et al 2020 ; Dakay et al 2020a , b ; Dakay et al 2020a , ...…”

Ischemic Stroke: An Underestimated Complication of COVID-19

“…Despite the characteristic symptoms of respiratory distress, less than 2% of hospitalized patients with COVID-19 have an ischemic stroke [9,14,15,117]. The exact stroke pathophysiology following SARS-CoV-2 infection remains to be established by autopsies and pathology reports.…”

“…As mentioned above, although the incidence of acute ischemic stroke was relatively low during hospitalization due to COVID-19, ranging from 1% to 6%, the mortality associated with it is substantially high, reaching as high as 38% [14,15]. Multivariate analysis demonstrated that patients with COVID-19 have more severe strokes and poorer outcomes compared with non-COVID-19 stroke [16].…”

Pathophysiologic mechanisms of cerebral endotheliopathy and stroke due to Sars-CoV-2

“…69 Down-regulation of ACE2 by Sars-CoV-2 binding may trigger relative down-regulation of the protective effects of ACE2/AT 2 R/MasR signaling and weaken the BBB. 70,71 Alternatively, endothelial invasion of the virus may activate a variety of inflammatory cascades that are known to impact BBB integrity. As in the case of identifying molecular pathways promoting viral susceptibility, recognition of the influence of these downstream signaling mechanisms on BBB integrity may inform our broad understanding of hemorrhagic stroke.…”