key: cord-0919136-x4uadmok
authors: Avula, Akshay; Nalleballe, Krishna; Narula, Naureen; Sapozhnikov, Steven; Dandu, Vasuki; Toom, Sudhamshi; Glaser, Allison; Elsayegh, Dany
title: COVID-19 presenting as stroke
date: 2020-04-28
journal: Brain Behav Immun
DOI: 10.1016/j.bbi.2020.04.077
sha: c0249d8f90c919f975e6cfc588b78d59f5e19800
doc_id: 919136
cord_uid: x4uadmok

Abstract Objective Acute stroke remains a medical emergency even during the COVID-19 pandemic. Most patients with COVID-19 present with constitutional and respiratory symptoms, some patients present with atypical symptoms including gastrointestinal, cardiovascular, or neurological symptoms. Here we present a series of four COVID-19 patients with acute stroke as a presenting symptom. Methods We searched the hospital databases for patients presenting with acute strokes and suspected COVID-19 features. All patients that had imaging confirmed strokes and PCR confirmed COVID-19 were included in the study. Patients admitted to the hospital with PCR confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data were obtained from electronic medical records. Informed consent was obtained. Results We identified four patients presenting with imaging confirmed acute strokes and PCR confirmed SARS-CoV-2 infection. We elucidate the clinical characteristics, imaging findings, and the clinical course. Conclusions Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke. Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and dawn appropriate personal protective equipment in every suspected patient. Further studies are urgently needed for a comprehensive understanding of the neurological pathology of COVID-19 and its effects on the nervous system.

In December 2019, the first reports of the corona Virus Disease 2019 (COVID-19) -an illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -emerged from Wuhan, Hubei Province, China. 1 Since then, this disease has become a worldwide pandemic, with over one-hundred thousand deaths to date. 2, 3 Symptoms of SARS-Cov-2 infection range from asymptomatic disease to life-threatening acute respiratory distress syndrome (ARDS), severe pneumonia, acute kidney injury (AKI), myocarditis, eventual multiorgan failure, and death. 4, 5 Recent literature reported multiple neurological manifestations including cerebrovascular accidents in patients with severe infection. 6 So far, there are no reported cases of COVID-19 presenting with strokes in the literature. Here, we report a case series of four patients that presented with ischemic stroke in the setting of PCR-confirmed SARS-CoV-2 infection.

We searched the hospital database for patients presenting with acute strokes and suspected COVID-19 features. All patients that had imaging confirmed strokes and PCR confirmed COVID-19 were included in the study. Patients admitted to the hospital with PCR confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data was obtained from electronic medical records. Informed consent was obtained.

We identified four patients that presented with imaging confirmed acute stroke and PCR confirmed COVID-19 disease. We elucidate the clinical characteristics, imaging findings, and the clinical course. Laboratory data are presented in table 1.

73-year-old male with a past medical history of hypertension, dyslipidemia, and carotid stenosis presented to the emergency department(ED) with fever, respiratory distress, and altered mental status. Review of systems was positive for dyspepsia, nausea, vomiting, reduced oral intake for two days, and negative for fevers or chills at home. He had a sick contact at home. Vital signs on presentation were fever of 101, tachycardia with heart rate(HR) of 102, hypoxemia with saturating 85% on 100% non-rebreather. The patient was intubated in the ED for hypoxic segment ( Figure 4B ). No arrhythmias were noted on telemetry. Patient was treated with aspirin, statins, and was discharged to a rehab facility with an event monitor.

To our knowledge, this is the first series of PCR confirmed COVID-19 cases presenting as cerebrovascular accident. In the study of Mao et.al, 5.7% of patients developed cerebrovascular disease later in the course of illness in patients with severe infection. 6 In a study by Li Y et.al, the incidence of stroke in COVID-19 patients was about 5% with a median age of 71.6 years. 7 These patients were associated with severe disease and had a higher incidence of risk factors like hypertension, diabetes, coronary artery disease, and previous cerebrovascular disease. 7 Average time of onset of stroke after COVID-19 diagnosis was 12 days. 7 Elevated CRP and D-dimer indicating high inflammatory state and abnormalities with coagulation cascade respectively might play in role in strokes with COVID-19 infection. 7 All the four cases in our report presented with cerebrovascular accident rather in early stages of illness.

The SARS-CoV-2 virus formerly called the novel coronavirus is the seventh coronavirus that infects humans. 8 

affected about 8000 patients with few reports of neurological manifestations, mostly peripheral neuropathy and encephalitis. 10 Similar to SARS-CoV-1, current SARS-CoV-2 affects the neurological system in about 36.7% as per Mao et.al. 6 Most coronavirus are neurotropic, similarly few studies speculate that SARS-CoV-2 is neurotropic. 11 Furthermore, there are reports of SARS-CoV-2 being identified in cerebrospinal fluid by PCR. 12 Angiotensin converting enzyme -2 (ACE) receptors are the major entry points for SARS-Cov-2 and other coronaviruses. 13 Although ACE-2 receptors are present on the nervous system, various pathophysiology have been proposed to explain the entry of SARS-CoV-2 into the nervous system -direct injury (blood and blood brain barrier), hypoxic injury, ACE2 receptors, immune injury. 11, 14 The pathophysiology behind the cerebrovascular accidents is still to be determined. Recent bacterial or viral infections have been known to cause strokes by increasing cardioembolism as well as arterio-arterial embolism. 15 16 Another study looking at activated partial thromboplastin time-based clot waveform analysis(CWA) in COVID-19 patients concluded that CWA parameters demonstrate hypercoagulability that precedes or coincides with severe illness. 17 Multiple reports of pulmonary embolism are currently available in the literature. 18 Autopsy and pathology findings are scarcely available, but recent autopsy findings suggest thrombotic microangiopathy in multiple organs especially in the lungs. [19] [20] [21] No autopsy reports of the brain are available at the time of this writing. With this evidence, the most plausible mechanism of early cerebrovascular accidents could be hypercoagulability leading to macro and micro thrombi formation in the vessels. Other 22 Outside transfers should be minimized, and even the ones that need transfer should have an infectious screening before the transfer. 22 A dedicated neurology hot-spot along with a mobile CT unit for COVID-19 patients with stroke-like symptoms is beneficial. 23 Clinically stable patients after thrombolysis can be monitored on non-intensive care units. 23

Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and dawn appropriate personal protective equipment in every suspected patient. Plans should be developed not to neglect the management of acute cerebrovascular accidents, even though the control of COVID-19 infection is our biggest priority. More research is needed to identify the neurological implications of COVID-19 disease. 

Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2. J Med Virol 2020. 2. WHO Director-General's opening remarks at the media briefing on

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

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Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease

Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study

Neurological manifestations in severe acute respiratory syndrome

Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19

A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2

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Incidence of thrombotic complications in critically ill ICU patients with COVID-19

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Acute pulmonary embolism and COVID-19 pneumonia: a random association?

Vander Heide RS. Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans

COVID-19 Autopsies

Protected Code Stroke: Hyperacute Stroke Management During the Coronavirus Disease

Large artery ischaemic stroke in severe acute respiratory syndrome (SARS)