Response by Ishida et al Regarding Article, “SARS-CoV-2 and Stroke in a New York Healthcare System”
Koto Ishida, Jose Torres, Shadi Yaghi
Abstract
HomeStrokeVol. 51, No. 11Response by Ishida et al Regarding Article, "SARS-CoV-2 and Stroke in a New York Healthcare System" Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse by Ishida et al Regarding Article, "SARS-CoV-2 and Stroke in a New York Healthcare System" Koto Ishida, Jose Torres and Shadi Yaghi Koto IshidaKoto Ishida Department of Neurology, New York University School of Medicine. , Jose TorresJose Torres https://orcid.org/0000-0001-6026-4938 Department of Neurology, New York University School of Medicine. and Shadi YaghiShadi Yaghi https://orcid.org/0000-0003-0031-1004 Department of Neurology, New York University School of Medicine. Originally published26 Oct 2020https://doi.org/10.1161/STROKEAHA.120.031606Stroke. 2020;51:e316–e317In Response:We thank Sajeev et al1 for their interest in our article and for the interesting discussion regarding proposed mechanism of cerebral thrombogenesis in the setting of coronavirus disease 2019 (COVID-19) infection. We read with great interest their prior reports demonstrating significantly higher plasma ACE2 (angiotensin-converting enzyme 2) activity in patients with embolic stroke of undetermined source.2Prior investigations have provided evidence for ACE2 expression in multiple extra-pulmonary organs and tissues including blood vessels.2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to and downregulates ACE2 potentially promoting cerebral and other tissue injury, inflammation, and vasoconstriction by unchecked ACE1 and angiotensin II. In contrast, mouse models suggest a protective benefit of neuronal over-expression of ACE2 in cerebral ischemic injury.3 We also read with great interest a recent study by Monteil et al4 demonstrating direct infection of blood vessels by SARS-CoV-2 in engineered human blood vessel organoids. Furthermore, they determined that early administration of human recombinant soluble ACE2 could significantly inhibit this infection.We agree that given the disproportionate representation of cryptogenic subtype in patients with stroke infected with SARS-CoV-2 virus (65.6% versus 30.4% in contemporary noninfected controls, P=0.003), this interaction represents a physiologically plausible mechanism. Although there are other theoretical mechanisms of stroke in patients with COVID-19 infection including cerebral hypoperfusion in critically ill ventilated patients, sepsis induced coagulopathy or embolization, stress cardiomyopathy with depressed ventricular function, and atrial fibrillation, we did not find significant differences in cardioembolic mechanism in particular or other noncryptogenic stroke subtypes in patients with compared with those without COVID-19 infection in our cohort.Several reports have highlighted the substantial decline in emergency room presentations of acute stroke during this global pandemic.5 In addition to this widespread limitation, given the presence of competing vascular risk factors and mechanisms, current data are insufficient to not only confirm causal relationship between SARS-CoV-2 and stroke, but also to determine specific mechanism of stroke in this population. We reported on embolic stroke of undetermined source and ASCOD (atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection) phenotyping for all patients. By grading all diseases present in a given patient, the ASCOD classification captures overlap between multiple competing high risk mechanisms and additionally documents the presence of underlying diseases unlikely to be causally related. Both classifications provide more granular data beyond the expansive cryptogenic categorization which includes patients with incomplete work-up. For instance, we found that out of the 21 patients with cryptogenic stroke, 10 patients (48%) did not complete the minimum diagnostic evaluation required to satisfy the embolic stroke of undetermined source criteria and thus only 11 patients (34%) met the embolic stroke of undetermined source criteria. This highlights the need for more studies.We join our colleagues in supporting the urgent need for persistent efforts to increase public awareness and education about the emergent nature of stroke and the importance of seeking immediate care even in the setting of a pandemic. We look forward to the findings of ongoing and future epidemiological and clinical research studies reporting on the association between COVID-19 infection and stroke as well as those investigating the mechanisms linking SARS-CoV-2 to specific mechanisms of cerebrovascular injury.DisclosuresDr Yaghi has unfunded research collaborations with Medtronic. The other authors report no conflicts.FootnotesThis article was sent to Marc Fisher, Senior Consulting Editor, for editorial decision and final disposition.For Disclosures, see page e317.References1. Yaghi S, Ishida K, Torres J, Mac Grory B, Raz E, Humbert K, Henninger N, Trivedi T, Lillemoe K, Alam S, et al. SARS-CoV-2 and stroke in a New York healthcare system.Stroke. 2020; 51:2002–2011. doi: 10.1161/STROKEAHA.120.030335LinkGoogle Scholar2. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.J Pathol. 2004; 203:631–637. doi: 10.1002/path.1570CrossrefMedlineGoogle Scholar3. Chen J, Zhao Y, Chen S, Wang J, Xiao X, Ma X, Penchikala M, Xia H, Lazartigues E, Zhao B, et al. Neuronal over-expression of ACE2 protects brain from ischemia-induced damage.Neuropharmacology. 2014; 79:550–558. doi: 10.1016/j.neuropharm.2014.01.004CrossrefMedlineGoogle Scholar4. Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, Hurtado Del Pozo C, Prosper F, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2.Cell. 2020; 181:905–913.e7. doi: 10.1016/j.cell.2020.04.004CrossrefMedlineGoogle Scholar5. Zhao J, Li H, Kung D, Fisher M, Shen Y, Liu R. Impact of the COVID-19 epidemic on stroke care and potential solutions.Stroke. 2020; 51:1996–2001. doi: 10.1161/STROKEAHA.120.030225LinkGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. 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Вишнева Е and Веснина Н (2021) Ишемический инсульт и covid‑19: механизмы патогенеза, клинические характеристики и трудности лечения в условиях пандемии, Естественные и Технические Науки, 10.37882/2223-2966.2021.04.11:№04, (185-192), . Escober Torres J, Alvarez Y, Bú E, Bú J and Soto M (2020) Internal Carotid Artery Thrombosis in COVID 19. Case report., Colombia Medica, 10.25100/cm.v51i3.4560 Gavriatopoulou M, Korompoki E, Fotiou D, Ntanasis-Stathopoulos I, Psaltopoulou T, Kastritis E, Terpos E and Dimopoulos M (2020) Organ-specific manifestations of COVID-19 infection, Clinical and Experimental Medicine, 10.1007/s10238-020-00648-x, 20:4, (493-506), Online publication date: 1-Nov-2020. November 2020Vol 51, Issue 11 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.120.031606PMID: 33104484 Originally publishedOctober 26, 2020 PDF download Advertisement SubjectsCerebrovascular Disease/Stroke