key: cord-0951072-hhizj2ks authors: Al-Mufti, Fawaz; Becker, Christian; Kamal, Haris; Alshammari, Hussein; Dodson, Vincent; Nuoman, Rolla; Dakay, Katarina; Coper, Jared; Gulko, Edwin; Kaur, Gurmeen; Sahni, Ramandeep; Scurlock, Corey; Mayer, Stephan A.; Gandhi, Chirag D. title: Acute Cerebrovascular Disorders and Vasculopathies associated with Significant Mortality in SARS-CoV-2 patients admitted to the Intensive Care Unit in The New York Epicenter date: 2020-11-02 journal: J Stroke Cerebrovasc Dis DOI: 10.1016/j.jstrokecerebrovasdis.2020.105429 sha: 34d53a42232809bfee5845d79df1eefc7308703b doc_id: 951072 cord_uid: hhizj2ks The current Coronavirus pandemic due to the novel SARS-Cov-2 virus has proven to have systemic and multi-organ involvement with high acuity neurological conditions including acute ischemic strokes. We present a case series of consecutive COVID-19 patients with cerebrovascular disease treated at our institution including 3 cases of cerebral artery dissection including subarachnoid hemorrhage. Knowledge of the varied presentations including dissections will help treating clinicians at the bedside monitor and manage these complications preemptively. The current Coronavirus pandemic due to the novel SARS-Cov-2 virus has proven to have systemic and multi-organ involvement alongside typical respiratory symptoms 1 . Among neurological manifestations, multiple reports reflect emerging evidence for neurotropism of the novel SARS-CoV-2 virus, including frequent complaints of anosmia, seizures and less common reports of acute inflammatory demyelinating polyneuropathy, acute necrotizing encephalitis etc 2 . A hypercoagulable state has also been reported in many patients, characterized by thrombocytopenia, elevated fibrinogen and d-dimer levels leading to unusual cases of multifocal pulmonary thrombosis as well as acute ischemic strokes [3] [4] [5] [6] . SARS-CoV-2 virus has also been implicated in autoimmune and autoinflammatory disease leading to a vasculopathy and/or vasculitides 1 among mounting reports of spontaneous coronary artery and cerebral artery dissection in COVID-19 patients without any history of antecedent trauma or connective tissue disorder (7) (8) (9) (10) (11) . Here, we describe a subset of consecutive COVID-19 patients with acute cerebrovascular disease (CVD) including 3 unique cases of spontaneous cerebral artery dissection. As our knowledge of the different afflictions of this virus grows, it is important for clinicians to be aware of the far reaching clinical consequences they may be faced with while providing optimal care to our patients. To our knowledge, this is the largest number of reported cases of cerebral artery dissection among COVID-19 patients from a single center. We report a prospectively followed cohort of all hospitalized cases with confirmed COVID-19 infection (SARS-CoV-2 RT-PCR positive) and CVD (ischemic and hemorrhagic stroke) between March 26th and April 12th, 2020 treated at our comprehensive stroke center located in the New York City Metropolitan area. Diagnosis of CVD was confirmed on neuroimaging with CT, CTA and/or MRI of the brain. Baseline demographics, clinical, laboratory, diagnostic and imaging findings were extracted by a board-certified or boardeligible neurologist. Stroke etiology, according to the TOAST criteria for ischemic stroke, was determined based on available workup. We cared for approximately 600 COVID-19 patients between March 26 th and April 12 th , 2020, of whom 127 were admitted to the ICU. We admitted a total of 48 patients with acute ischemic stroke during the study period, 8 of whom had concomitant COVID-19 and were managed in the COVID Intensive care unit. Of the eight COVID-19 positive patients, seven (87%) patients presented with acute ischemic stroke (AIS) ( Table 1, (Table 2) . Three of the eight COVID-19 positive patients were found to have extracranial and/or intracranial dissections seen on CTA/MRA and confirmed with diagnostic cerebral angiography. Two patients had extracranial dissections involving the cervical segment of the internal carotid artery, and one had concomitant dissection of the supraclinoid segment of the internal carotid artery with associated diffuse subarachnoid hemorrhage. One of these patients had presented with a non-aneurysmal convexity subarachnoid hemorrhage and was found to have concomitant dissections of the middle cerebral artery and extracranial V2 segment of the vertebral artery. This patient subsequently developed delayed ischemic injury due cerebral vasospasm (Table 1 , 2). None of the patients with cerebral dissections had any known risk factors such as connective tissue disorders, vasculopathy, recent history of trauma or cervical manipulations to explain the dissections. The average age, presenting APACHE IVa scores as well as severity of the COVID-19 in patients with cerebrovascular disorders was similar to those with no cerebrovascular disorders ( Table 3 ). The average APACHE IVa Score for ICU deaths of the COVID-19 patients with no cerebrovascular involvement compared to COVID-19 patients with cerebrovascular involvement was similarly high in both groups (97.5 vs 89.5). One patient was discharged from the intensive care unit, and five patients (63%) required intubation with mechanical ventilation per the ARDSNet protocol. None of the COVID-19 patients with cerebrovascular involvement were extubated compared to a 19% (25/127) extubation rate in the COVID-19 ICU patients with no cerebrovascular involvement. Of the COVID-19 patients with cerebrovascular disease, 3(37.5%) died in the ICU while on mechanical ventilation, while the other 4(50%) could not be weaned off mechanical ventilation and were transferred to long term care facilities with tracheostomy on ventilators. Of the 8 patients with COVID-19 with cerebrovascular involvement, 3 patients progressed to a Glasgow Coma Scale of 3 with evidence of cerebral edema as well as severe ARDS and eventually died. One patient was discharged home independent while the other 4 were discharged to long term care facility on mechanical ventilation needing full time care. In addition, the average duration to progression to a modified Rankin Score (mRS) of 5/6 was 2 days with an average length of stay of 5.1 days for the COVID-19 patients with CVD compared to 8.1 days for the patients with no cerebrovascular symptoms. The rate of mortality or end-of-life in the ICU in the COVID-19 patients with CVD was 37.5% (3/8), compared to 24% (31/127) in the COVID-19 patients with no cerebrovascular involvement. As the incidence of COVID-19 exponentially multiplies around the world, there is mounting evidence for its association with cerebrovascular disease as well as a predisposition for a hypercoagulable state secondary to a DIC-like condition and alteration of the coagulation pathways 4,12 . Our COVID-19 patients with spontaneous dissections and SAH or AIS fared worse than others which further added to the morbidity and mortality of these patients already dealing with multi-organ failure. While the mechanism of action leading to a vasculopathy remains multifactorial, our case series adds important literature to the growing volume of case reports describing spontaneous coronary 8, 9 , aortic 10 and carotid 11 dissections among patient afflicted with COVID-19. Viral illnesses have been linked to cranial and cervical dissections in prior studies with viral replication causing direct vascular injury or vascular damage as a result of immune response activation secondary to proinflammatory cytokines, free radicals, and proteases 12, 13 . SARS-COVID-2 causes damage to endothelial cells, activating inflammatory and thrombotic pathways 14 . It can be postulated that a vasculitic process similar to that seen with varicella zoster virus 15 , in which viral replication in the cerebral arterial wall triggers local inflammation may be responsible for causing spontaneous dissections [15] [16] [17] . Additionally, virus binding to the CNS ACE II receptors may lead to disruption of its autoregulatory function causing blood pressure elevations leading to vessel wall damage predisposing to dissections 18, 19 . Implicated mechanisms for ischemic stroke in COVID-19 patients include inflammation, prothrombotic coagulopathy and endothelial injury. The strong inflammatory response alongside elevated D-dimer levels and often noted anti-phospholipid antibodies leads to high rates of coagulopathy leading to embolic strokes which fits with the stroke sub-type seen in our patient cohort [3] [4] [5] . Empiric low dose anticoagulation has been considered to be effective in preventing strokes in critically sick patients with COVID-19 20 . As our understanding of the multiple pathways of action of COVID-19 continues to improve, knowledge and awareness of these added complications will help clinicians to pro-actively monitor and perhaps manage these conditions better. There are several limitations to these observations. This is a single center report and while it may not be generalizable, our study represents the first series of reported dissections among COVID-19 patients. While it is possible that the association of severity of COVID and cerebral dissections may or may not be a direct one, further reporting of cases and larger cohort registries will help elucidate the natural history of these spontaneous infectious dissections and add to the literature. In conclusion, based on the presumption that the infection with the COVID-19 virus results in a hyperinflammatory cascade, and consequently hypercoagulability, intensivists should have a high index of suspicion for cerebrovascular complications in the setting of this pandemic. Our institution's preliminary experience suggests a higher incidence and mortality of acute cerebrovascular disease in COVID-19 patients admitted to the ICUs. Further studies exploring the use of antiplatelets early in the course of COVID-19 related cerebrovascular disorders and specifically cerebrovascular dissections are needed as this contributes to a significant percentage of the overall ICU mortality. 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