key: cord-0780819-2e3vmdx4
authors: Shekhar, Rahul; Sheikh, Abu Baker; Suriya, Sajid S.; Upadhyay, Shubra; Zafar, Atif
title: Neurological Complications Among Native Americans with COVID-19: Our Experience at a Tertiary Care Academic Hospital in the U.S.
date: 2020-08-24
journal: J Stroke Cerebrovasc Dis
DOI: 10.1016/j.jstrokecerebrovasdis.2020.105260
sha: 49771b80e83a830268bbe543d7ac7a5a8b09c852
doc_id: 780819
cord_uid: 2e3vmdx4

OBJECTIVE: To study the central nervous system (CNS) complications in patients with COVID-19 infection especially among Native American population in the current pandemic of severe acute respiratory syndrome virus (COVID-19). METHODS: Patients with confirmed COVID-19 infection at University of New Mexico hospital (UNMH) were screened for development of neurological complications during Feb 01 to April 29, 2020 via retrospective chart review. RESULTS: Total of 90 hospitalized patients were screened. Out of seven patients, majority were Native Americans females, and developed neurological complications including subarachnoid hemorrhage (SAH), Intraparenchymal hemorrhage (IPH), Ischemic stroke (IS) and seizure. All 7 patients required Intensive care unit (ICU) level of care. Patients who developed CNS complications other than seizure were females in the younger age group (4 patients, 38-58 years) with poor outcome. Out of 7, three developed subarachnoid hemorrhage, two developed ischemic infarction, and four developed seizure. Two patients with hemorrhagic complication expired during the course of hospitalization. All three patients with seizure were discharged to home. CONCLUSION: Patients with serious CNS complications secondary to COVID-19 infection were observed to be Native Americans. Patients who developed hemorrhagic or ischemic events were observed to have poor outcomes as compared to patients who developed seizures.

Severe acute respiratory syndrome (SARS-CoV-2), termed as COVID-19 has affected millions of people worldwide. It originated in the city of Wuhan, China and was formally declared as a pandemic by World Health Organization (WHO) on March 11th 2020. It has affected more than five million people and more than 100,000 deaths so far in United States. 1 Neurological complications seen in COVD-19 include involvement of both central nervous system (CNS) and peripheral nervous system (PNS). According to a recent study, neurological symptoms were seen in approximately 36% of the patients diagnosed with COVID-19. 2 Commonly reported CNS symptoms were dizziness, headache, metabolic encephalopathy, taste impairment, smell impairment, vision impairment and neuralgia.

Serious neurological complications such as stroke, and seizure, were also reported. 2, 3 Recent weekly report by centers for disease control and prevention (CDC) reported 0.7% of the US population experienced central nervous system (CNS) complications. 4 We share a case series of seven patients, all except one of whom, were Native Americans (NA), and experienced CNS complications during the admission of COVID-19.

Retrospective chart review of patients, admitted to University of New Mexico Health Science Center (UNMH) between Feb 01 to April 29, 2020, was done. Patients diagnosed with COVID-19 via reverse transcriptase-polymerase chain reaction (RT-PCR) from nasal swab were screened for development of neurological complications (ischemic stroke, intracerebral hemorrhage, sub-arachnoid hemorrhage, seizure, and encephalitis). Patients with peripheral neurological symptoms such as nerve pain, tingling and/or minor CNS symptoms like headache, mild dizziness, altered mental status without focal neurological signs, or metabolic encephalopathy, were excluded. The study was approved by UNMH institutional review board and was granted a waiver of informed consent.

A total of 90 patients with confirmed COVID-19 were screened. Out of 90 patients, 53(59%) were NA, 25(28%) were Caucasian, 4(4%) were African-American and 8(9%) were others.

Seven out of ninety (8%) were found to have neurological manifestations including SAH, IPH, IS and seizures, were included. Mean age was 55 years and majority (5 out of 7) were female (See Table 1 ). Six patients were Native Americans (NA) and one was Caucasian. All patients presented with symptoms of COVID-19 infection including fever, cough, shortness of breath and general body malaise. Five patients required emergent intubation. All 7 patients required intensive care unit (ICU) level of care.

The first four presenting with SAH, IPH, and IS, were NA females with age range 38 -58 years. All presented with subjective fevers, shortness of breath and cough. The neurological complication in these four patients was observed between 5-19 days of symptoms onset. Out of other three cases presenting with seizure, two were NA with age range 53-77 years. All three patients required intubation on presentation but two patients required it for seizure and were extubated within 2 days.

All seven patients were on deep venous thrombosis (DVT) prophylaxis with heparin since admission and this was continued appropriately as per clinical needs. None of the patients were treated with therapeutic anticoagulation. Overall length of stay was between 6-19 days and 2-17 days for ICU stay.

To the best of our knowledge, this is the first report sharing neurological complications in NA with COVID-19 infection. Native Americans, who make up less than 2 percent of the U.S. population, comprise 10 % of the population in state of New Mexico. Based on the CDC data, mortality among NA is higher compared to other ethnicities. 4 In recent reports, it was acknowledged that due to health care disparities and low socioeconomic status, NA were at increased risk of having conditions associated with COVID-19. 5 Moreover, in general population, NA have a higher incidence of Cerebrovascular accidents (CVA) compared to other ethnic groups. 6 Approximately 59% of patients managed at our center for COVID-19 infection were NA (51 out of 90) and 6 out of 7 patients with neurological complication were NA. Even though we have a small sample size, our data depicts a higher prevalence of neurological manifestations among NA with COVID-19. We believe that this is due to the known higher prevalence of vascular risk factors such as hypertension, smoking, atrial fibrillation, coronary artery disease, obesity, and alcohol abuse among the NA. 6 It is also worth noting that our patients had some unusual findings, especially the presence of IPH. We could not ascertain why our NA patients had a higher incidence of brain bleeds.

Klok et al. suggested that patients with severe COVID-19 have higher risk of thromboembolism due to procoagulant state. 7 Three out of four patients who had CVA, one was found to have venous sinus thrombosis. All of them had elevated d-dimer levels. None of these patients had any atrial arrhythmias or evidence of unstable thrombus or plaques. The ischemic stroke can be partly explained due to pro-thrombotic state with dysregulation of the clotting system secondary to intense inflammation related to cytokine storm leading to thrombus formation. 8 of patients with COVID -19 by genome sequencing. 9 A recently published case report from Japan did find viral RNA sequencing from CSF and claimed that the patient had meningitis who presented with seizures. 10 Since most of our patients made clinical recovery with supportive care, further invasive neurological investigation including CSF analyses was not performed, though initial brain imaging and electroencephalogram (EEG) was benign in all three patients.

The understanding of the pathophysiology behind neural involvement in COVID-19 is still in its infancy but various mechanisms have been proposed. Zhao, et al postulated that the virus binds to Angiotensin converting enzyme-2 (ACE2) receptors which are also present in vascular endothelial cells in the brain. 11 This is one of the potential mechanisms, how viruses can breach the blood brain barrier. Giacomelli et al showed presence of anosmia and dysgeusia as one of the early presenting symptoms suggesting involvement of olfactory and gustatory pathway. 12 Further investigations are needed to confirm the exact pathophysiology.

Our study has some limitations. It is a single center retrospective study and this data might not be applicable to the general population as the majority of our patients are NA. 

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 -United States

Disparities in the Population at Risk of Severe Illness From COVID-19 by Race/Ethnicity and Income

Abstract TMP49: Increasing Prevalence of Cerebrovascular Risk Factors in Native Americans With Ischemic Stroke

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

Atherosclerosis as Pathogenetic Substrate for Sars-Cov2

Nervous system involvement after infection with COVID-19 and other coronaviruses

A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

Single-cell RNA expression profiling shows that ACE2, the putative receptor of Wuhan 2019-nCoV, has significant expression in the nasal, mouth, lung and colon tissues, and tends to be co-expressed with HLA-DRB1 in the four tissues

Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study

Hgb: 12-16 g/dl, Platelet count: 150-400 x10 3 /µl, PT: 9.4-15.4 sec, INR: 0.80-1.30, aPTT: 26-38 sec

mg/dl, TG: <150 mg/dl, LDL: <100 mg/dl, HDL: >40 mg/dl, Cholesterol: <200 mg/dl, HgbA1c: >6.5%, Anti-cardiolipin antibodies: 0.0-9.9U/ml, Procalcitonin: <10ng/ml

Total Bili 0.3-1.2 mg/dl