key: cord-1032611-cqvcvqbk
authors: Elkhider, Hisham; Ibrahim, Faisal; Sharma, Rohan; Sheng, Sen; Jasti, Madhu; Lotia, Mitesh; Kapoor, Nidhi; Onteddu, Sanjeeva; Mueed, Sajjad; Allam, Hesham; Nalleballe, Krishna
title: COVID-19 and Stroke, a Case Series and review of literature
date: 2020-11-04
journal: Brain Behav Immun Health
DOI: 10.1016/j.bbih.2020.100172
sha: 047330619ab9633ffefb608943120cbb3a4bd7dd
doc_id: 1032611
cord_uid: cqvcvqbk

BACKGROUND: Corona Virus Disease 2019 (COVID-19) cases continue to increase around the World. Typical symptoms include fever and respiratory illness but a constellation of multisystem involvement including central nervous system (CNS) and peripheral nervous system (PNS) have been reported with COVID-19. Acute ischemic strokes (AIS) have also been reported as a complication. METHODOLOGY: We analyzed patient characteristics, clinical outcomes, laboratory results and imaging results of four patients with COVID-19 who had AIS. RESULTS: All four patients were =< 60 years , had hypoxemic respiratory failure secondary to pneumonia, elevated D-dimer and inflammatory markers. CONCLUSION: Ischemic strokes are known complications in patients with severe COVID-19.

and 2). 60-year-old female with Past history of obstructive sleep apnea (OSA), hypertension and uncontrolled type 2 diabetes mellitus (DM) presented to the emergency department with cough, shortness of breath and fever after exposure to with a COVID-19 patient. She was obese with a Body mass index (BMI) of 36. Computed tomography (CT) of the chest revealed multifocal predominantly peripheral ground-glass opacities. She tested positive for COVID-19, and was admitted for further management. One day after admission she developed sudden onset right facial droop, right-sided weakness and slurred speech with National Institutes of Health Stroke Scale (NIHSS) of 6 (moderate stroke). CT head without contrast showed no intracranial hemorrhage (ICH) and intravenous tissue plasminogen activator (IV tPA) was given. CT Angiogram showed no large vessel occlusion. She eventually improved and Magnetic resonant imaging (MRI) of the brain was performed 24 hours later showed punctate bilateral embolic cortical infarcts ( Figure 1 ). She was still febrile up to 38.9 C, and her labs showed low white blood cells (WBC) 2.7 K/uL with lymphopenia 0.6 K/CUMM, Platelets 179 K/uL. She had elevated hypercoagulability markers including D-Dimer > 4000 ng/ml and fibrinogen 125 mg/dL (normal 200-393 mg/dL), in J o u r n a l P r e -p r o o f addition to elevated inflammatory markers including C-reactive protein (CRP) of 160 mg/L (normal less than 10), ferritin of 602 ng/ml (normal 10.0-300) and procalcitonin of 4.2 ng/ml (normal 0.00 -0.10). Transthoracic echocardiogram (TTE) was normal with no evidence of left ventricular thrombus, normal ejection fraction and left atrial index (LAI). Patient improved to NIHSS of 3 (minor stroke). She was treated with Aspirin and Atorvastatin for secondary stroke prevention, and was discharged to inpatient rehabilitation. Event monitor showed no arrhythmias.

The hypercoagulability markers and inflammatory markers were elevated in this patient and the cause of stroke is likely COVID-19 causing hypercoagulability. infection have noted to develop a hyperinflammatory state followed by a prothrombotic state that is frequently complicated by both venous and arterial thromboembolism [15, 16] . Simultaneous multiple LVO of different vascular territories has been consistently reported and was postulated to be secondary to the prothrombotic state induced by COVID-19 [17] .

A study compared the stroke characteristics of COVID-19 positive patients with COVID-19

negative patients and historical controls. In this it was observed that patients with concomitant J o u r n a l P r e -p r o o f COVID-19 suffered severe strokes, with a higher NIHSS score with a greater proportion of large vessel occlusion [10] . AIS in COVID-19 patients have worse outcomes in the form of higher hemorrhagic transformation and all-cause mortality. Embolic events as noted by elevated ddimer, serum cardiac markers including high-sensitivity troponin and proBNP have been consistently reported [18] .

COVID-19 has been very well reported to cause endothelial cell inflammation, apoptosis and dysfunction within arteries, arterioles, capillaries, venules and veins which in turn lead to tissue hypoperfusion, thrombosis and vascular dysfunction [19, 20] . Patients with severe COVID-19

infection have noted to develop a hyperinflammatory state secondary to a cytokine storm which produced a vasculitic picture causing strokes. The exaggerated and uncontrolled activation of the immune system causing excessive cytokine release has been consistently reported in patients with severe pulmonary disease. Cytokine storm is diagnosed with the presence of elevated plasma markers of inflammation like C-reactive protein, erythrocyte sedimentation rate, procalcitonin, ferritin, interleukins (IL2, IL6, IL-7), granulocyte -colony-stimulating factor and tumor necrosis alpha [21] .

of the heart, small bowel, brain, kidneys, and lungs [22] . improvement following immunomodulating treatment [24] .

Cardiac involvement is common in patients with COVID-19. Myocardial involvement mostly presents as an acute cardiac injury. This has been defined by elevated serum cardiac biomarkers and abnormal findings in the echocardiogram of an infected patient [25] Patients are also reported to be at a higher risk of arrhythmia secondary to myocarditis possibly precipitating embolism [25, 26, 27, 28] .

Arrhythmias, such as atrial fibrillation, are more frequent in COVID-19 cardiomyopathy as inflammation is a substrate for atrial arrhythmias. Ventricular arrhythmias are also observed and J o u r n a l P r e -p r o o f may accompany cardiac arrest in these patients [29] . It is very well known historically that Afib poses an increased risk of Cardio-embolic strokes.

Historically, viral infections like influenza have been shown to have a slightly increased risk of stroke in the past. In similar lines, severe infection with COVID-19 has been shown to have an increased risk of AIS. A study showed that the risk of acute ischemic stroke in patients admitted with COVID-19 was 1.6% versus 0.2% for patients admitted with influenza [30] . The mechanism of the apparent increase in the risk of stroke in COVID-19 patients is not clear. 

Epub ahead of print

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