key: cord-0923417-oliw4ee5 authors: Sweid, Ahmad; Hammoud, Batoul; Weinberg, Joshua H; Oneissi, Mazen; Raz, Eytan; Shapiro, Maksim; DePrince, Maureen; Tjoumakaris, Stavropoula; Gooch, Michael R; Herial, Nabeel A; Zarzour, Hekmat; Romo, Victor; Rosenwasser, Robert H; Jabbour, Pascal title: Letter: Thrombotic Neurovascular Disease in COVID-19 Patients date: 2020-06-04 journal: Neurosurgery DOI: 10.1093/neuros/nyaa254 sha: 7c34db8c593206fe90c4cd9afe0c959a9a49ea81 doc_id: 923417 cord_uid: oliw4ee5 nan To the Editor: Although the respiratory system is the primary target of the coronavirus, studies have demonstrated a strong tropism to the central nervous system (CNS). 1, 2 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. This receptor is also found in the CNS and plays a crucial role in autoregulating cerebral perfusion pressure. 3, 4 Additionally, epidemiological data demonstrated increased mortality due to cardiovascular and cerebrovascular diseases during flu pandemics due to a hypercoagulable state. 5, 6 The triad of neuroinvasion of SARS-CoV-2, induction of hypercoagulable state, [5] [6] [7] [8] [9] and the inhibition of ACE2 blocking the formation of Angiotensin (1-7) serve as the pathophysiology for neurovascular insults. 3, 4 We present a case series of coronavirus disease 2019 (COVID-19) patients from 2 health systems developing cerebrovascular insult. Institutional Review Board (IRB) approved the study protocol and waived the need for informed consent. A retrospective analysis was conducted across 2 institutions between March 20 and April 10, 2020. Fourteen patients were identified with the diagnosis of cerebrovascular insult and COVID-19 infection. COVID-19 was diagnosed using reverse-transcriptase/polymerase-chain-reaction assays of nasopharyngeal samples for SARS-CoV-2. Medical charts were queried for baseline patient characteristics, comorbidities, COVID-19 symptoms, duration between COVID-19 symptoms and the neurological manifestation, cerebrovascular insult, National Institutes of Health Stroke Scale (NIHSS) at presentation, procedure details, and mortality. The relevant anonymized patient-level data are available on reasonable request from the authors. All procedures performed in the studies involving human participants were per the ethical standards of the IRB or National Research Committee, and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was reviewed and approved by the Thomas Jefferson University Institutional Review Board. Following our institutional guidelines, all protected health information were removed, and individual patient consent was not required for the analysis of this case series. The total sample size was 14 patients. The mean age was 60.1 ± 11.1 yr, and 9 patients were males (64.3%). Six patients (42.8%) had no significant prior medical history. Seven patients (50.3%) had neurological insult as the initial manifestation of COVID-19. The average duration between the onset of COVID-19 symptoms and the cerebrovascular insult was 3.5 d (range: 0-17). The cerebrovascular pathologies were 12 cases of acute ischemic stroke (AIS) and 2 cases of sinus thrombosis. The mean NIHSS was 15.8 (range: 1-30), and all patients were treated within 6 h of symptoms onset. A total of 4 patients had carotid T occlusions, 2 had tandem occlusion (internal carotid artery [ICA] and middle cerebral artery [MCA] M1 occlusion), 1 patient had M1 and A2 occlusion, 2 patients had M1 occlusion, 2 patients had M2 occlusion, 2 patients had sinus thrombosis, and 1 patient had central retinal artery occlusion. Two patients developed hemorrhagic conversion requiring decompressive surgery. The mean duration of the mechanical thrombectomy (MT) procedures was 95.5 min (range: 17-428), and a favorable thrombolysis in cerebral infarction (TICI) score (>2b) was achieved in all patients. The total mortality incidence was 6 (42.8%; Table) . Despite the small sample size, the data demonstrate some unusual trends worth sharing, at least to draw awareness. First, the mean age of the population was 60 yr, 42% of the cohort was younger than 55, and 42% did not have any traditional cerebrovascular risk factors. Moreover, cerebrovascular insult was the primary manifestation of COVID-19 in patients who did not have the fulminant virus manifestations present. Occlusions occurred in multiple arterial territories and both on the arterial and on the venous sides; the latter are more challenging to treat, and the procedures require additional expertise. Selected procedures were more complex and challenging, requiring multiple attempts to retrieve the clot entirely due to the severe clot burden. Such an observation is evident in the relatively long procedure time compared to historical data. Also, mortality rates reached 42.8%, with TICI ≥2b achieved in all cases. Two patients developed hemorrhagic conversion requiring decompressive hemicraniectomy (Figure 1 ). The level of causality between the SARS-CoV-2 and AIS is yet to be determined. However, maintaining a vigilant attitude is crucial, specifically if it leads to favorable outcomes. It is early to determine the exact impact of COVID-19 on the incidence of acute cerebrovascular diseases. The SARS-CoV-2 is neuroinvasive and neurovirulent ( Figure 2 ), 1,2 binds to ACE2 and reduces its downstream effect (Figure 3) , 3, 4 and induces a hyperinflammatory response characterized by a cytokine storm ( Figure 4 ). [7] [8] [9] This leads to vasculitis, 10 increased sympathetic tone, arrhythmias, and a hypercoagulable state. Unusual trends have been seen in AIS patients who are COVID-19 positive; while it is too early to establish direct causality, our preliminary data can be used to raise awareness in the population. We are seeing younger patients with no risk factors presenting with AIS and MT procedures are more challenging to deal with. It is crucial in pandemic times to watch and follow closely noteworthy trends and investigate and report new findings. Possible central nervous system infection by SARS coronavirus Coronavirus infection of the central nervous system: host-virus stand-off Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target ACE2/ANG-(1-7)/Mas pathway in the brain: the axis of good Influenza and stroke risk: a key target not to be missed? Temporal relationship between influenza infections and subsequent first-ever stroke incidence COVID-19: consider cytokine storm syndromes and immunosuppression Thromboinflammation and the hypercoagulability of COVID-19 Coagulopathy and antiphospholipid antibodies in patients with Covid-19 Endothelial cell infection and endotheliitis in COVID-19 Copyright C 2020 by the Congress of Neurological Surgeons Dr Jabbour is a consultant for Medtronic and MicroVention. Dr Tjoumakaris and Dr Gooch are consultants for Stryker. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.