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Revista Ecuatoriana de Neurología

versão On-line ISSN 2631-2581versão impressa ISSN 1019-8113

Rev Ecuat Neurol vol.29 no.1 Guayaquil Jan./Abr. 2020

 

Review Article

Neurologic Manifestations Associated With SARS-Cov-2 Infection: A Neuro-Review Of COVID-19

Manifestaciones Neurológicas Asociadas A La Infección Por SARS-Cov-2: Una Neuro-Revisión De COVID-19

Rocío Santibáñez-Vásquez1 

Angelina Freire-Bonifacini1 

Daniel Moreno-Zambrano2 

Martha Arévalo-Mora3 

Rocío García-Santibáñez4 

1Universidad Católica De Santiago De Guayaquil. Guayaquil, Ecuador.

2Hospital Los Ceibos del Instituto de Ecuatoriano de Seguridad Social. Guayaquil, Ecuador. <danielmorenozambrano@gmail.com>

3Universidad de Especialidades Espíritu Santo. Samborondón, Ecuador.

4Emory University , School of Medicine, Department of Neurology. Atlanta, United States


Abstract

Background:

In December 2019, multiple cases of pneumonia of unknown etiology surged in China. In January 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was the identified cause. The World Health Organization (WHO) defined the condition as “Coronavirus 2019 Disease” (COVID-19). In February, its presence was confirmed in South America and Ecuador. On March 11th, the WHO declared COVID-19 as a pandemic. This condition mainly afflicts the respiratory system. However, reports of neurological manifestations in confirmed COVID-19 patients have recently emerged.

Methods:

Multiple databases were reviewed, the information was extracted and analyzed independently by 3 authors.

Results:

Neurological manifestations associated with COVID-19 were identified. Including: myalgia, headache, altered mental status, cerebrovascular events, dizziness, hypogeusia, hyposmia, neuropathic pain, visual impairment, ataxia, seizures, Central Hypoventilation Syndrome, encephalopathy, rhabdomyolysis, Acute Hemorrhagic Necrotizing Encephalopathy, Guillain Barre Syndrome (GBS), meningitis and encephalitis.

Conclusion:

COVID-19 is associated with neurological involvement. It is most frequently observed in cases that are severe, atypical, and with comorbidities. Health care providers and neurologists alike, must remain alert and keep high suspicion of severity when these manifestations are present. Timely recognition might help initiate early treatment and isolation, preventing clinical decline and viral spread.

Keywords: Coronavirus; SARS-CoV-2; COVID-19; Neurology; Pandemic

Resumen

Antecedentes:

En diciembre de 2019, múltiples casos de neumonía de etiología desconocida surgieron en China. En enero de 2020, el Coronavirus 2 del Síndrome Respiratorio Agudo Severo (SARS-CoV-2) fue identificado como su causa. La Organización Mundial de la Salud (OMS) definió la afección por este virus como “Enfermedad por Coronavirus 2019” (COVID-19). En febrero se confirmó su presencia en Sudamérica y en el Ecuador. El 11 de marzo, la OMS declaró a COVID-19 como una pandemia. Esta patología afecta principalmente al sistema respiratorio. Sin embargo, reportes de manifestaciones neurológicas en pacientes con COVID-19 han empezado a emerger.

Métodos:

Múltiples bases de datos fueron revisadas, la información fue extraída y analizada independientemente por 3 autores.

Resultados:

Manifestaciones neurológicas asociadas a COVID-19 fueron identificadas. Incluyendo: mialgia, cefalea, alteración de la consciencia, eventos cerebrovasculares, mareo, hipogeusia, hiposmia, neuralgia, alteración de la agudeza visual, ataxia, crisis epilépticas, Síndrome de Hipoventilación Central, encefalopatía, rabdomiólisis, Encefalopatía Necrotizante Hemorrágica Aguda, Síndrome de Guillain Barré (SGB), meningitis y encefalitis.

Conclusión:

COVID-19 está asociado a compromiso neurológico. Se observa con mayor frecuencia en casos severos, atípicos y con comorbilidades presentes. Proveedores de la salud y neurólogos deben estar alertas y tener un bajo umbral de sospecha frente a estas manifestaciones. El reconocimiento oportuno de estas podría ayudar a iniciar tratamiento y aislamiento temprano, previniendo el agravamiento clínico y la diseminación del virus.

Palabras claves: Coronavirus; SARS-CoV-2; COVID-19; Neurología; Pandemia

Introduction

In December 2019, pneumonia cases of unknown etiology were identified in Wuhan city, Hubei Province of China. The cause, a novel enveloped RNA betacoronavirus which was isolated on January 7, 2020, later named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). On February 11th, The World Health Organization (WHO) defined the condition caused by this pathogen as “Coronavirus disease 2019” (COVID-19) (1). On February 27th, the first case in South America was confirmed in Brazil (2) and two days later, Ecuador’s (3) first case was reported as well. On March 11th, the WHO declared COVID-19 as a pandemic (4). During this outbreak, numerous studies have mainly described respiratory and gastrointestinal symptoms, distinctive laboratory findings, and characteristic pulmonary radiological abnormalities. But recently, Mao et al reported the first description (preprint) in February 2020 (now published in JAMA Neurology in April), focusing on neurological manifestations of SARS-CoV-2 infection (5).

Objective

To summarize the reported neurological manifestations caused by SARS-CoV-2 infection.

Methods

Three independent searches by authors (DMZ, MAM, and AFB) of articles published in English and Spanish in electronic databases, including Medline, EMBASE, BEI, Cochrane Library, Dialog Datastar, EBSCO Biomedical, ERIC, First Search, Scholar Google, BioRxiv, MedRxiv, and the surveillance system of the World Health Organization (WHO), the Pan American Health Organization (PAHO), the European Center for Disease Prevention and Control (CEPCE). Using the following keywords: "SARS-CoV-2", "COVID-19", "neurological manifestations", and "neurological associations"; between December 2019 and April 2020. The reference list of the selected articles was manually searched for any relevant data. There was no restriction for the review of the study in the articles searched. The bibliographic search was iterative, that is, finding materials until reaching theoretical saturation.

Results

We found a total of 24 relevant articles in our search. Huang et al. (6) were the first to report the clinical characteristics of 41 patients with confirmed COVID-19 on January 24, 2020, 8% of which presented with headache. Later in the month, Chen et al. (7) described a sample of 99 patients in which 8% exhibited headache, 9% consciousness impairment, and 11% myalgia. Eleven more studies were published by February; the most common manifestation reported was headache (4 - 34%), followed by myalgia (3.36 - 52%) (1)(5)(8)(9)(10)(11)(12)(13)(14)(15)(16); within these studies, Mao et al (5) published on February 25 a preprint (not peer reviewed) which was later published in JAMA Neurology on April, the first report with a neurological focus. The report consisted of 214 patients, 36.4% of which had neurological manifestations displaying a direct proportional relation to the severity of the clinical presentations; these included: dizziness (16.8%), headache (13.1%), muscle injury (10.7%), consciousness impairment (7.5%), hypogeusia (5.6%), hyposmia (5.1%), acute cerebrovascular event (2.8%), neuralgia (2.3%), visual impairment (1.4%), ataxia (0.5%), and seizures (0.5%). In March, 6 other similar studies (17)(18)(19)(20)(21)(22) reported muscular compromise as the most common symptom (5.49 - 61%), followed by headache (7.69 - 13%), and dizziness (2.4%). Among these, Li et al (17) described in an abstract preprint of the Lancet journal, the development of cerebrovascular events in patients with COVID-19; where 5% of the 221 subjects included presented with an ischemic stroke, 0.5% with cavernous sinus thrombosis, and 0.5% with a cerebral hemorrhage. These patients were more likely to present with cardiovascular risk factors and severe SARS-CoV-2. In April, Lechien et al, showed that up to 85.6% and 88% of patients could present olfactory and gustatory dysfunction respectively (23). These findings are summarized in Table 1. Recently, Li et al mentioned a possible Central Hypoventilation Syndrome in a 24-year-old female patient (24), Jin et al presented a case of rhabdomyolysis in a 60 year old male (25), Filatov et al a case of encephalopathy in a 74-year-old man (26), Poyiadji et al reported a female that developed acute hemorrhagic necrotizing encephalopathy (27), Zhao et al reported a 61 year old female with GBS during COVID-19 (28), and Moriguchi et al presented the first case of meningitis and encephalitis associated to SARS-CoV-2 infection (29). These cases are presented in Table 2. (Table 1)

Table 1 Neurological Manifestations related to SARS-CoV-2* Infection 

  Total (%)
Hypogeusia 5.6 - 88
Hyposmia 5.1 - 85.6
Myalgia 3.36 - 61
Headache 4 - 34
Impaired consciousness 7.5 - 16.25
Cerebrovascular event 2.8 - 6
Dizziness 2.4 - 16
Neuralgia 2.3
Visual disturbances 1.4
Ataxia 0.5
Seizures 0.5

*Severe Acute Respiratory Syndrome Coronavirus 2

Discussion

In October 2007, Cheng et al warned about the importance of public health preparedness for a coronavirus outbreak similar to the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV); this is due to the recombinant genetic capacity of these viruses, the presence of reservoirs in horseshoe bats, and the tradition of exotic mammal consumption in the southern China. He called it a “time bomb” and stressed on the need to be prepared for such an event should not be ignored (30). Today, 13 years later, we face a pandemic caused by the novel coronavirus SARS-CoV-2. Even though the main clinical manifestations are respiratory, there are reports on other clinical presentations such as the gastrointestinal (6.1%) (31) and cardiac as well (32). However, as the infection toll rises, other less common clinical presentations may surface, including those of neurological characteristics in nature.

The neuroinvasive potential of SARS-CoV-2 has been previously postulated (24)(33), but not demonstrated. Once transmitted through respiratory droplets, aerosol, or by direct contact, SARS-CoV-2 enters the host's cells through the angiotensin-converting enzyme receptor 2 (ACE 2); which is widely expressed in various tissues including the respiratory tract, lungs, endothelium, and the central nervous system (CNS). Animal studies have shown various pathways by which coronaviruses could enter the CNS. Either through the olfactory nerves, invading areas such as the brainstem and thalamus; or by invading peripheral nerve terminals and then gaining access to the CNS using a synaptic pathway through the respiratory system, once it has already established contact with the ACE 2 receptor (33). Available evidence cites similar coronaviruses such as SARS-CoV and MERS-CoV, Hemagglutinating Encephalomyelitis Virus 67 (HEV67), Human Coronavirus OC43 (HCV-OC43) or Avian Bronchitis Virus (ABV). In these studies, viral antigens have been detected in the brainstem, especially in regions that include the solitary tract and the ambiguous nucleus. The nucleus of the solitary tract receives sensory information from lung mechanoreceptors and chemoreceptors, and the respiratory tract; while efferent fibers from the nucleus ambiguous and the solitary tract nucleus provide innervation to glands, airway smooth muscle and blood vessels.

Such neuroanatomical interconnections could indicate that the death of infected animals or even humans may be due to dysfunction of the cardiorespiratory centers in the brainstem, pointing out that the respiratory dysfunction in COVID-19 may have a neurogenic component. (24)

Although there is no abundant evidence to date regarding neuroinvasion by SARS-CoV-2, reports of neurological manifestations in hospitalized patients with COVID-19 have begun to emerge (5)(17)(23)(24)(25)(26)(27)(28)(29). These manifestations seem to more likely present in patients with risk factors such as high blood pressure, diabetes mellitus, previous cerebrovascular disease, advanced age, severe clinical conditions, lymphopenia, elevated C-reactive protein and D-Dimer. These patients may have fewer typical symptoms such as fever and cough, but are more likely to have muscle injury, impaired consciousness, and acute cerebrovascular disease; the latter could be associated with a hypercoagulable state demonstrated by D-Dimer elevations. (5)(17) (Table 2)

Table 2 Neurological Associations Reported for SARS-CoV-2 Infection * 

Reports Authors and Date Sex Age Comorbidities
Central Hypoventilation Syndrome± Li et al Feb 27 2020 Female 24 Not reported
Encephalopathy Filatov et al Mar 21 2020 Male 74 Multiple**
Rhabdomyolysis Jin et al Mar 20 2020 Male 60 Not reported
Acute Hemorrhagic Necrotizing Encephalopathy Poyiadji et al Mar 31 2020 Female Not reported Not reported
Guillain Barre syndrome Zhao et al Apr 1 2020 Female 61 Not reported
Meningitis Moriguchi et al Apr 3 2020 Male 24 Not reported
Encephalitis Moriguchi et al Apr 3 2020 Male 24 Not reported

* Severe Acute Respiratory Syndrome Coronavirus 2. ± Possible. ** Atrial Fibrillation, Ischemic Cerebrovascular Disease, Parkinson's Disease, Chronic Obstructive Pulmonary Disease.

Musculoskeletal manifestations are common in COVID-19. Muscle injury with elevated creatine kinase and lactate dehydrogenase levels was observed in severely ill patients; (5) its presence becomes important since it is known that a possible complication is rhabdomyolysis (25). Hyposmia and dysgeusia have recently been reported by the Spanish Society of Neurology and other medical societies as symptoms of SARS-CoV-2 infection (34), and that their presence could reach 85.6% and 88% respectively (23). The first could be explained by CoVs’ tendency to invade the olfactory bulbs (23) and it’s potential to compromise the CNS. Consciousness impairment has been demonstrated as another manifestation of COVID-19; it could be due to direct or indirect involvement, since there are reports in which the virus was detected in the cerebrospinal fluid in a patient with meningoencephalitis (29) and not in the other (26). In these cases, headache could be a symptom of meningeal involvement (35), especially if it presents with neck stiffness (NS) (29); an interesting clinical manifestation since most viral meningitis do not present NS and this sign has been observed in SARS-CoV-2 meningitis. COVID-19 has been associated with epileptogenic activity (0.5%) (5) that could indicate direct injury to the temporal lobe due to encephalitis (29). In addition to being found in tears, there is evidence that SARS-CoV-2 can compromise the conjunctiva (36), which in turn could be the origin of hypopsy (decreased visual acuity).

Although to the moment, injury to the retina and optic nerve has only been demonstrated by other CoVs. (37) Also, ataxia and dizziness have previously been described in similar CoVs infections. (38)

A significant fact is that SARS-CoV-2 has been associated with cases of Acute Hemorrhagic Necrotizing Encephalopathy (27) and GBS (28). Other associated and post-infectious complications have already been reported with other CoVs such as encephalitis, Critical Illness Polyneuromyopathy, myopathy, Refractory Epileptic Status, Indeterminate Acute Flaccid Paralysis, Brainstem Encephalitis, Acute Disseminated Encephalomyelitis, and GBS (Table 3) (38)(39)(40)(41)(42)(43)(44)(45)(46). The latter takes on special importance, since neuralgia (5) is a peripheral neurological manifestation observed in COVID-19. Proposing that in addition to acute virulence, there could be chronic complications; this is in accordance with existing evidence that has demonstrated the persistent presence in glia and possibly in similar CoVs neurons that would be related to perennial neuropathological changes (47).

Table 3 Neurological Associations Reported by Infection with other Coronaviruses 

Reports Authors and Date Sex Age Comorbidities Coronavirus
Encephalitis Hung et al 2003 & Morfopoulou et al 2016 Female & Male 59 & 11 months IgA Nephropathy & SCID. * SARS - CoV** & HCoV-OC43
Critical Illness Polyneuromyopathy Tsai et al 2004 Female 51, 48 & 42 Not reported SARS - CoV**
Myopathy Tsai et al 2004 Male 31 Not reported SARS - CoV**
Refractory Epileptic Status Lau et al 2004 Female 32 26 Week Pregnancy SARS - CoV**
Indeterminate Acute Flaccid Paralysis Turgay et al 2015 Female 3 Not reported HCoV-OC43 & HCoV-229E
Severe Acute Disseminated Encephalomyelitis Yeh et al 2004 & Arabi et al 2017 Male 15 & 74; 45 Not reported & DM, HTN, HLD; DM, HTN, CKD, IHD. * HCoV-229E & MERS-CoV
Central Nervous System Vasculopathy Arabi et al 2017 Male 57 DM, HTN, PVD* MERS-CoV
Post-Infectious Brain Stem Encephalitis Kim et al 2017 Male 55 AF, DM, HTN, ERC, HT* MERS-CoV
Guillain Barré Syndrome Kim et al 2017 & Sharma et al 2019 Male 55 & 5 FA, DM, HTN, ERC, HT* & Not reported MERS-CoV & HCoV-OC43

*⨥Expressed in years unless otherwise stated. *SCID (Severe Combined Immunodeficiency Disease), DM (Diabetes Mellitus), HTN (Hypertension), HLD (Hyperlipidemia), CKD (Chronic Kidney Disease), IHD (Ischemic Heart Disease), FA (Atrial Fibrillation), HT (Hypothyroidism), PVD (Peripheral Vascular Disease); **SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus); ∑ Human Coronavirus OC43, ⨍ Human Coronavirus 229E ⋕ Middle East Respiratory Syndrome Coronavirus.

Reports of neurological compromise on COVID-19 are on the rise. Timely recognition is significant since it is more common in patients with severe and atypical clinical conditions, (5) which could occur in the absence of respiratory or gastrointestinal manifestations. Healthcare providers and neurologists should pay close attention to this and should have a high index of suspicion when evaluating patients in an endemic area; especially since the knowledge of this is evolving. Effective identification could initiate early treatment and early isolation; preventing a clinical aggravation and spread of the virus (48). Currently, due to mobility restrictions and lack of service provided by outpatient clinics, elective care is not extensively available. Because of this, the use of telemedicine is a growing need and guidelines for the management of COVID-19 have currently been developed for this purpose (49). This pandemic is likely to catalyze the widespread adoption of teleneurology during and after the public control of this disease has been achieved (50); since specialists in neurology may not always be readily available in person for the evaluation of cases. Detailed knowledge of these manifestations and associations will help to provide better care to patients, either through telemedicine or inpatient care.

Conclusion

SARS-CoV-2 infection is associated with neurological compromise. It is mainly observed in severe cases, in patients with comorbidities, and atypical presentations. General healthcare providers and neurologists should pay close attention to this and have a high index of suspicion due to the fluency with which new information is reported. Timely recognition could help initiate early treatment and isolation, preventing clinical aggravation and spread of the virus.

References

Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China [published online ahead of print, 2020 Feb 28]. N Engl J Med. 2020;10.1056/NEJMoa2002032. doi:10.1056/NEJMoa2002032 [ Links ]

World Health Organization. Coronavirus disease 2019 (COVID-19): situation report-38. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200227-sitrep-38-covid-19.pdf?sfvrsn=2db7a09b_4 2020. [ Links ]

World Health Organization. Coronavirus disease 2019 (COVID-19): situation report-41. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200301-sitrep-41-covid-19.pdf?sfvrsn=6768306d_2. 2020. [ Links ]

World Health Organization. Coronavirus disease 2019 (COVID-19): situation report-51. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10. 2020 [ Links ]

Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. Published online April 10, 2020. doi:10.1001/jamaneurol.2020.1127 [ Links ]

Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China [published correction appears in Lancet. 2020 Jan 30;:]. Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5 [ Links ]

Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513. doi:10.1016/S0140-6736(20)30211-7 [ Links ]

Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China [published online ahead of print, 2020 Feb 7]. JAMA. 2020;e201585. doi:10.1001/jama.2020.1585 [ Links ]

Chang D, Lin M, Wei L, et al. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China [published online ahead of print, 2020 Feb 7]. JAMA. 2020;323(11):1092-1093. doi:10.1001/jama.2020.1623 [ Links ]

COVID-19 National Emergency Response Center, Epidemiology and Case Management Team, Korea Centers for Disease Control and Prevention. Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea. Osong Public Health Res Perspect. 2020;11(1):8-14. doi:10.24171/j.phrp.2020.11.1.03 [ Links ]

Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series [published correction appears in BMJ. 2020 Feb 27;368:m792]. BMJ. 2020;368:m606. Published 2020 Feb 19. doi:10.1136/bmj.m606 [ Links ]

Xu YH, Dong JH, An WM, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2 [published online ahead of print, 2020 Feb 25]. J Infect. 2020;S0163-4453(20)30100-6. doi:10.1016/j.jinf.2020.02.017 [ Links ]

Yang W, Cao Q, Qin L, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China [published online ahead of print, 2020 Feb 26]. J Infect. 2020;S0163-4453(20)30099-2. doi:10.1016/j.jinf.2020.02.016 [ Links ]

Tian S, Hu N, Lou J, et al. Characteristics of COVID-19 infection in Beijing [published online ahead of print, 2020 Feb 27]. J Infect. 2020;S0163-4453(20)30101-8. doi:10.1016/j.jinf.2020.02.018 [ Links ]

Xu X, Yu C, Qu J, et al. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2 [published online ahead of print, 2020 Feb 28]. Eur J Nucl Med Mol Imaging. 2020;10.1007/s00259-020-04735-9. doi:10.1007/s00259-020-04735-9 [ Links ]

Wu J, Liu J, Zhao X, et al. Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study [published online ahead of print, 2020 Feb 29]. Clin Infect Dis. 2020;ciaa199. doi:10.1093/cid/ciaa199 [ Links ]

Li Yanan, Wang Mengdie, Zhou Yifan, Chang Jiang, Xian Ying, Mao Ling, Hong Candong, Chen Shengcai, Wang Yong, Wang Hailing, Li Man, Jin Huijuan, Hu Bo. Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study (3/3/2020). Preprint at SSRN: https://ssrn.com/abstract=3550025 [ Links ]

Zhao W, Zhong Z, Xie X, Yu Q, Liu J. Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study [published online ahead of print, 2020 Mar 3]. AJR Am J Roentgenol. 2020;1-6. doi:10.2214/AJR.20.22976 [ Links ]

Cheng Z, Lu Y, Cao Q, et al. Clinical Features and Chest CT Manifestations of Coronavirus Disease 2019 (COVID-19) in a Single-Center Study in Shanghai, China [published online ahead of print, 2020 Mar 14]. AJR Am J Roentgenol. 2020;1-6. doi:10.2214/AJR.20.22959 [ Links ]

Mo P, Xing Y, Xiao Y, et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China [published online ahead of print, 2020 Mar 16]. Clin Infect Dis. 2020;ciaa270. doi:10.1093/cid/ciaa270 [ Links ]

Han R, Huang L, Jiang H, Dong J, Peng H, Zhang D. Early Clinical and CT Manifestations of Coronavirus Disease 2019 (COVID-19) Pneumonia [published online ahead of print, 2020 Mar 17]. AJR Am J Roentgenol. 2020;1-6. doi:10.2214/AJR.20.22961 [ Links ]

Qian GQ, Yang NB, Ding F, et al. Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series [published online ahead of print, 2020 Mar 17]. QJM. 2020;hcaa089. doi:10.1093/qjmed/hcaa089 [ Links ]

Lechien JR, Chiesa-Estomba CM, De-Siati DR et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol (2020). https://doi.org/10.1007/s00405-020-05965-1 [ Links ]

Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients [published online ahead of print, 2020 Feb 27]. J Med Virol. 2020;10.1002/jmv.25728. doi:10.1002/jmv.25728 [ Links ]

Jin M, Tong Q. Rhabdomyolysis as Potential Late Complication Associated with COVID-19 [published online ahead of print, 2020 Mar 20]. Emerg Infect Dis. 2020;26(7):10.3201/eid2607.200445. doi:10.3201/eid2607.200445 [ Links ]

Filatov A, Sharma P, Hindi F, et al. (March 21, 2020) Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy. Cureus 12(3): e7352. doi:10.7759/cureus.7352 [ Links ]

Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features [published online ahead of print, 2020 Mar 31]. Radiology. 2020;201187. doi:10.1148/radiol.2020201187 [ Links ]

Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? The Lancet Neurology. 2020 Apr 1;0(0). 10.1016/S1474-4422(20)30109-5 [ Links ]

Moriguchi T, Harii N, Goto J, et al. A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2 [published online ahead of print, 2020 Apr 3]. Int J Infect Dis. 2020;S1201-9712(20)30195-8. doi:10.1016/j.ijid.2020.03.062 [ Links ]

Cheng VC, Lau SK, Woo PC, Yuen KY. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev. 2007;20(4):660-694. doi:10.1128/CMR.00023-07 [ Links ]

Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis [published online ahead of print, 2020 Mar 13]. Travel Med Infect Dis. 2020;101623. doi:10.1016/j.tmaid.2020.101623 [ Links ]

Inciardi RM, Lupi L, Zaccone G, et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19) [published online ahead of print, 2020 Mar 27]. JAMA Cardiol. 2020;10.1001/jamacardio.2020.1096. doi:10.1001/jamacardio.2020.1096 [ Links ]

Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms [published online ahead of print, 2020 Mar 13]. ACS Chem Neurosci. 2020;10.1021/acschemneuro.0c00122. doi:10.1021/acschemneuro.0c00122 [ Links ]

SEN A. Covid-19: Recomendaciones de la Sociedad Española de Neurología (SEN) en relación con la pérdida de olfato como posible síntoma precoz de infección por CoVID-19 [Internet]. [cited 2020 Mar 25]. Available from: http://www.sen.es/noticias-y-actividades/222-noticias/covid-19-informacion-para-pacientes/2663-covid-recomendaciones-de-la-sociedad-espanola-de-neurologia-sen-en-relacion-con-la-perdida-de-olfato-como-posible-sintoma-precoz-de-infeccion-por-covid-19 [ Links ]

Nath A. Neurologic complications of coronavirus infections. Neurology. 2020 Mar 27;10.1212/WNL.0000000000009455. [ Links ]

Wu P, Duan F, Luo C, et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. Published online March 31, 2020. doi:10.1001/jamaophthalmol.2020.1291 [ Links ]

Seah I, Agrawal R. Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals [published online ahead of print, 2020 Mar 16]. Ocul Immunol Inflamm. 2020;1-5. doi:10.1080/09273948.2020.1738501 [ Links ]

Arabi YM, Harthi A, Hussein J, et al. Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV). Infection. 2015;43(4):495-501. doi:10.1007/s15010-015-0720-y [ Links ]

Hung EC, Chim SS, Chan PK, et al. Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome. Clin Chem. 2003;49(12):2108-2109. doi:10.1373/clinchem.2003.025437 [ Links ]

Morfopoulou S, Brown JR, Davies EG, et al. Human Coronavirus OC43 Associated with Fatal Encephalitis. N Engl J Med. 2016;375(5):497-498. doi:10.1056/NEJMc1509458 [ Links ]

Tsai LK, Hsieh ST, Chao CC, et al. Neuromuscular disorders in severe acute respiratory syndrome. Arch Neurol. 2004;61(11):1669-1673. doi:10.1001/archneur.61.11.1669 [ Links ]

Lau KK, Yu WC, Chu CM, Lau ST, Sheng B, Yuen KY. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis. 2004;10(2):342-344. doi:10.3201/eid1002.030638 [ Links ]

Turgay C, Emine T, Ozlem K, Muhammet SP, Haydar AT. A rare cause of acute flaccid paralysis: Human coronaviruses. J Pediatr Neurosci. 2015;10(3):280-281. doi:10.4103/1817-1745.165716 [ Links ]

Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics. 2004;113(1 Pt 1):e73-e76. doi:10.1542/peds.113.1.e73 [ Links ]

Kim JE, Heo JH, Kim HO, et al. Neurological Complications during Treatment of Middle East Respiratory Syndrome. J Clin Neurol. 2017;13(3):227-233. doi:10.3988/jcn.2017.13.3.227 [ Links ]

Sharma K, Tengsupakul S, Sanchez O, Phaltas R, Maertens P. Guillain-Barré syndrome with unilateral peripheral facial and bulbar palsy in a child: A case report. SAGE Open Med Case Rep. 2019;7:2050313X19838750. Published 2019 Mar 21. doi:10.1177/2050313X19838750 [ Links ]

Arbour N, Ekandé S, Côté G, et al. Persistent infection of human oligodendrocytic and neuroglial cell lines by human coronavirus 229E. J Virol. 1999;73(4):3326-3337. [ Links ]

Jin H, Hong C, Chen S, Zhou Y, Wang Y, Mao L, et al. Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists. Stroke Vasc Neurol. 2020 Apr 1;svn-2020-000382. [ Links ]

Greenhalgh T, Koh GCH, Car J. Covid-19: a remote assessment in primary care. BMJ. 2020;368:m1182. Published 2020 Mar 25. doi:10.1136/bmj.m1182 [ Links ]

Klein BC, Neil A. COVID-19 is catalyzing the adoption of teleneurology. BusisNeurology 2020, 10.1212/WNL.0000000000009494; DOI:10.1212/WNL.0000000000009494. [ Links ]

Received: March 02, 2020; Accepted: April 03, 2020

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