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 Table of Contents  
Year : 2020  |  Volume : 37  |  Issue : 1  |  Page : 1-3

COVID-19 associate neurological complications

1 Department of Neurology, Trakya University, Faculty of Medicine, Edirne, Turkey
2 Department of Neurology, Akdeniz University, Faculty of Medicine, Antalya, Turkey

Date of Submission30-Mar-2020
Date of Decision02-Apr-2020
Date of Acceptance06-Apr-2020
Date of Web Publication8-May-2020

Correspondence Address:
Leyla Baysal-Kirac
Department of Neurology, Trakya University Hospital, Edirne
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2636-865X.283930

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2019-novel Coronavirus disease (COVID-19) is a global health problem that affected >2.000.000 people in the world. Although the main component of the disease is pulmonary disturbances, recent reports suggested neurological manifestations. Neurological complications have been rarely reported with other Coronavirus associated diseases. In this short review, we would like to draw attention to COVID-19-related neurological symptoms. Heath-care providers should be aware that COVID-19 can associate neurological manifestations.

Keywords: Anosmia, coronavirus disease-2019, Middle East respiratory syndrome, severe acute respiratory syndrome

How to cite this article:
Baysal-Kirac L, Uysal H. COVID-19 associate neurological complications. Neurol Sci Neurophysiol 2020;37:1-3

How to cite this URL:
Baysal-Kirac L, Uysal H. COVID-19 associate neurological complications. Neurol Sci Neurophysiol [serial online] 2020 [cited 2023 May 29];37:1-3. Available from: http://www.nsnjournal.org/text.asp?2020/37/1/1/283930

2019-novel Coronavirus disease (COVID-19) threatened global health with a virus spread >114 countries. This disease reported to have affected >2.460.792 people and caused 168.934 deaths until April 20, 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the beta-coronavirus family as two other highly pathogenic CoVs causing SARS which emerged in China in 2002 and the Middle East respiratory syndrome (MERS) which emerged in Saudi Arabia in 2012.[1],[2] COVID-19 has been identified to share a similar infection mechanism with pneumonia induced by SARS-CoV and MERS-CoV.[3] The entry of SARS-Cov-2 into human host cells has been shown to use the same receptor as SARS-CoV; cellular-receptor angiotensin-converting enzyme 2 (ACE2), which is expressed mainly in the respiratory tract.[4] ACE2, the functional receptor of SARS-CoV expressed not only on lung alveolar epithelial cells but also on enterocytes of the small intestine and arterial and venous endothelial cells and arterial smooth muscle cells in all of the organs.[5] COVID-19 leads to highly fatal pneumonia similar to those reported for SARS and MERS.[6]

Previous reports proved that other CoVs leading SARS and MERS can rarely associate neurological complications. Large artery ischemic stroke, axonal neuropathy, rhabdomyolysis, and olfactory neuropathy have been reported with SARS.[7],[8] Neuromuscular complications, including Guillain-Barré syndrome (GBS), have been associated with MERS.[9] In a pediatric patient, acute flaccid paralysis associated with human CoV 229E and OC43 co-infection has been reported.[10] It is not known whether SARS-CoV-2 has a potential for neuroinvasion and plays a role in neurological diseases. Although COVID-19 can lead mainly lower respiratory tract problems, one study from COVID-19 designed hospitals in Wuhan, China, demonstrated more than one-third of Coronavirus patients presented with neurological syndromes including headache, altered consciousness, evidence of skeletal muscle damage, and acute cerebrovascular disease.[11] This report from Wuhan, China, summarized demographic and clinical features of 214 confirmed cases of hospitalized COVID-19 patients retrospectively. Nearly 37% of the patients presented with central nervous system symptoms (CNS), including dizziness, headache, and peripheric nervous system symptoms, including hypogeusia and hyposmia. Patients with severe infections were older and more likely to have comorbid diseases like hypertension, and manifested more frequently with neurological symptoms, including acute cerebrovascular disease (5.7% vs. 0.8%), disturbances of consciousness (14.8% vs. 2.4%), and muscle injury (19.3% vs. 4.8%) compared to nonsevere disease. The authors suggested considering SARS-CoV-2 infection as a differential diagnosis in patients with neurological symptoms during the epidemic period of COVID-19.[11] One another report described a patient diagnosed with COVID-19 pneumonia and developed rhabdomyolysis as a late complication on the 9th day of hospital admission. The patient presented with pain and weakness in lower limbs with very high creatinine kinase and myoglobin levels in the blood. Aggressive fluid therapy, maintaining acid-base balance, and continuing treatment with antivirals led prompt recovery.[12] Another report from the United States presented a 74-year-old patient with the past medical history of atrial fibrillation, cardioembolic stroke, Parkinson's disease and mental status, fever, and cough. Computed tomography scan of the head and lumbar puncture revealed nonspecific findings. The electroencephalogram showed bilateral slowing and focal slowing in the left temporal region with sharp waves. Later on, the patient was tested positive for SARS-CoV-2, developed respiratory failure, and delivered to the intensive care unit.[13] One recent report described a patient with a 3-day history of cough, fever and altered mental status, and diagnosed with COVID-19 pneumonia. The brain magnetic resonance imaging of the head revealed hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions. Cerebrospinal fluid (CSF) findings were nonspecific. The patient was diagnosed with COVID-19-related acute hemorrhagic necrotizing encephalopathy and started on intravenous immunoglobulin (IVIG) treatment.[14] Another novel report presented a patient with acute progressive lower extremity weakness without fever and respiratory symptoms. Later on, the patient was diagnosed with GBS based on abnormal electromyography findings and CSF results and treated with IVIG. On the 8th day of follow-up, the patient developed dry cough and fever. Oropharyngeal swabs were positive for SARS-CoV-2, and the patient was transferred immediately to the infection isolation room. The authors speculated that SARS-CoV-2 infection might have been responsible for the development of GBS.[15]

Previous experimental studies in transgenic mice models showed CoVs could enter the brain via olfactory nerves and invade CNS. Especially, the brain stem has been shown to be heavily infected by SARS-CoV and MERS-CoV.[16],[17],[18] Although the exact route for CNS invasion not known, increasing evidence reveals that CoVs gain access to CNS via a synapse-connected route.[18],[19] It is suggested that since SARS-CoV and SARS-CoV-2 share a high similarity, the potential invasion of SARS-CoV-2 may be partially responsible for the acute respiratory failure of patients with COVID-19 through destroying medullary neurons.[18]

Many of the patients with a neurological disease fall into high-risk categories for COVID-19 pneumonia that include older patients (>60 years), patients with comorbid diseases including hypertension, diabetes mellitus, lung and heart diseases. Especially multiple sclerosis patients who are using immunomodulatory treatment and patients with neuromuscular diseases having limited lung capacity might be under risk for COVID-19 related pneumonia. For pandemic control, several hospitals restricted hospital access and canceled elective procedures, which is concerning about neurological patient care. The SARS outbreak adversely affected seizure control because of antiepileptic drug withdrawal.[20] Establishing widely used telemedicine programs may help patient management and reduce the risk of viral spread.

In conclusion, in this pandemic era, patients with neurological symptoms should be carefully interpreted. As more patients expose to COVID-19, we will better understand the full disease spectrum and neurological manifestations.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Drosten C, Günther S, Preiser W, van der Werf S, Brodt HR, Becker S, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 2003;348:1967.  Back to cited text no. 1
Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012;367:1814-20.  Back to cited text no. 2
Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, et al. From SARS to MERS, Thrusting Coronaviruses into the spotlight. Viruses 2019;11:59.  Back to cited text no. 3
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020;395:565-74.  Back to cited text no. 4
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631-7.  Back to cited text no. 5
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.  Back to cited text no. 6
Tsai LK, Hsieh ST, Chang YC. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwan 2005;14:113-9.  Back to cited text no. 7
Hwang CS. Olfactory neuropathy in severe acute respiratory syndrome: Report of A case. Acta Neurol Taiwan 2006;15:26-8.  Back to cited text no. 8
Kim JE, Heo JH, Kim HO, Song SH, Park SS, Park TH, et al. Neurological complications during treatment of Middle East respiratory syndrome. J Clin Neurol 2017;13:227-33.  Back to cited text no. 9
Turgay C, Emine T, Ozlem K, Muhammet SP, Haydar AT. A rare cause of acute flaccid paralysis: Human coronaviruses. J Pediatr Neurosci 2015;10:280-1.  Back to cited text no. 10
[PUBMED]  [Full text]  
Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: A retrospective case series study. MedRxiv; 2020.  Back to cited text no. 11
Jin M, Tong Q. Rhabdomyolysis as potential late complication associated with COVID-19. Emerg Infect Dis 2020;26. doi: 10.3201/eid2607.200445.  Back to cited text no. 12
Filatov A, Sharma P, Hindi F, Espinoa PS. Neurological complications of coronavirus disease (COVID-19): Encephalopathy. Cureus 2020;12:e7352.  Back to cited text no. 13
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology 2020:201187. doi: 10.1148/radiol.2020201187.  Back to cited text no. 14
Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: Causality or coincidence? Lancet Neurol 2020. doi: 10.1016/S1474-4422(20)30109-5.  Back to cited text no. 15
Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 2008;82:7264-75.  Back to cited text no. 16
Li K, Wohlford-Lenane C, Perlman S, Zhao J, Jewell AK, Reznikov LR, et al. Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J Infect Dis 2016;213:712-22.  Back to cited text no. 17
Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 2020. doi: 10.1002/jmv.25728.  Back to cited text no. 18
Li YC, Bai WZ, Hirano N, Hayashida T, Taniguchi T, Sugita Y, et al. Neurotropic virus tracing suggests a membranous-coating-mediated mechanism for transsynaptic communication. J Comp Neurol 2013;521:203-12.  Back to cited text no. 19
Lai SL, Hsu MT, Chen SS. The impact of SARS on epilepsy: The experience of drug withdrawal in epileptic patients. Seizure 2005;14:557-61.  Back to cited text no. 20

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