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Neurological Manifestations As the Predictors of Severity and Mortality

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Neurological Manifestations As the Predictors of Severity and Mortality Amanat et al. BMC Neurology (2021) 21:116 https://doi.org/10.1186/s12883-021-02152-5 RESEARCH ARTICLE Open Access Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study Man Amanat1, Nima Rezaei2,3,4, Mehrdad Roozbeh5, Maziar Shojaei6, Abbas Tafakhori7, Anahita Zoghi6, Ilad Alavi Darazam8, Mona Salehi1, Ehsan Karimialavijeh9, Behnam Safarpour Lima6, Amir Garakani10,11, Alexander Vaccaro12 and Mahtab Ramezani13* Abstract Backgrounds: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID- 19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. Methods: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. Results: We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n=1) were also found during follow-up. Conclusion: Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak. Keywords: SARS-CoV-2, Anosmia, Headache, Neurology, Seizure, Stroke * Correspondence: [email protected] 13Department of Neurology, Skull Base Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Amanat et al. BMC Neurology (2021) 21:116 Page 2 of 12 Introduction infections (e.g. tuberculosis), loss of competence and no The novel virus from the coronaviridae family termed as access to surrogates, and withdrawal of consent. severe acute respiratory syndrome coronavirus 2 (SARS- The ethics committee of Shahid Beheshti University of CoV-2) was first discovered in December, 2019 after Medical Sciences approved the study. The protocol was many pneumonia cases with unknown cause were iden- explained to all participants and if they lacked decision- tified in Wuhan, China [1]. The SARS-CoV-2 is a β- making capacity, their legal surrogates were informed coronavirus which is an enveloped virus with helical nu- about the study. The printed protocol was also given. It cleocapsid and non-segmented positive ribonucleic acid was explained that participation in the study was op- that can infect mammals [2–5]. The World Health tional and the identity information would remain confi- Organization (WHO) declared coronavirus disease 2019 dential and not published. Written informed consent (COVID-19) as a pandemic outbreak on March 11th, was obtained before the initiation of the study. 2020. Over 80 million confirmed cases and about 2 mil- lion deaths due to COVID-19 were recorded until the Data collection end of 2020 [6]. All eligible inpatients were interviewed and the demo- Several non-respiratory symptoms have been reported graphic characteristics including gender, age, smoking in individuals with COVID-19. The reports of neuro- status, and co-morbidities were recorded. Participants logical features are increasing but few large sample-sized were examined and chest computed tomography (CT) studies reported the incidence of neurological disorders was performed in all cases. The laboratory tests included in people with COVID-19. Myalgia, headaches, and loss cell blood count, quantitative C-reactive protein (CRP), of smell (anosmia) and taste (dysgeusia) sensations are lactate dehydrogenase (LDH), and procalcitonin. The se- common neurological findings of the disease [7–9]. Re- verity of COVID-19 was determined using American cent studies showed that SARS-CoV-2 could manifest as Thoracic Society recommendations for community- life-threatening neurological conditions including ische- acquired pneumonia [18]. mic stroke, subarachnoid hemorrhage, status epilepticus, To assess neurological manifestations, two neurolo- and acute demyelinating encephalomyelitis [10–13]. gists with at least 5 years of experience took a detailed Neurological symptoms were also reported in epidemic history and examined all participants. Any disagreement outbreaks of other coronaviruses including SARS-CoV was resolved by discussion with each other or consult- and the Middle East respiratory syndrome (MERS)-CoV ation with another neurologist. Headaches were known [14, 15]. The direct invasion of coronaviruses to the ner- to be associated with COVID-19 if they fulfilled the cri- vous system and over-production of pro-inflammatory teria for ‘Headache attributed to systemic viral infection’ cytokines could be the plausible underlying mechanisms according to the International Classification of Headache [16]. This study aimed to determine the incidence of Disorders [19]. Brain CT and/or magnetic resonance im- neurological manifestations in hospitalized cases with aging (MRI), electroencephalography (EEG), electro- COVID-19 and assess these symptoms as predictors of myography and nerve conduction velocity (EMG-NCV), severity and death. as well as cerebrospinal fluid (CSF) analysis were con- ducted if clinically indicated. Smell and taste dysfunc- Methods tions were assessed in cases using a self-reporting tool. Study design and participants The National Institute of Health stroke scale (NIHSS) This was a prospective hospital-based cohort study con- was used to evaluate the severity of ischemic stroke. The ducted in Loghman, Imam Hossein, and Imam Kho- NIHSS was designed to objectively quantify neurological meini hospitals, the three major referral hospitals in impairments in stroke and consisted of 11 items [20]. Tehran province, Iran. Males and females aged above 18 Each item can be scored from 0 to 4 and the total pos- years who were diagnosed with COVID-19 based on sible scores ranged from 0 to 42. Neurological impair- WHO recommendations [17] were included in the ments can be divided into four categories using NIHSS: study. The sterile nasopharyngeal swabs were inserted in a. mild (0–4), b. moderate (5–15), c. Moderate to severe one nostril of each participant. The collected specimens (16–20), and d. severe (21–42). The intracerebral were placed into tubes containing viral transport hemorrhage (ICH) score was also calculated in partici- medium; stored at 4o Cto8o C and were sent to labora- pants with ICH. This is a clinical grading scale using tories within 12 h. The positive results of real-time Glasgow Coma Scale, age, the presence of infratentorial reverse-transcription polymerase chain reaction (RT- origin, ICH volume, and the presence of intraventricular PCR) assay using a SARS-CoV-2 nucleic acid detection hemorrhage to predict the ICH mortality [21]. The total kit (PCR Fluorescence Probing of Sansure Biotech, score ranged from 0 to 6. Changsha, China) could confirm COVID-19. The exclu- Most included cases were followed for 8 weeks after sion criteria were the presence of other respiratory discharge from hospital
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