Vol 54, No 5 (2020)
Review Article
Published online: 2020-07-15

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Neurological manifestations of SARS-CoV-2 — a systematic review

Stanisław Słyk1, Izabela Domitrz2
Pubmed: 32667047
Neurol Neurochir Pol 2020;54(5):378-383.

Abstract

Introduction. Following two coronaviral epidemics in 2002 and 2012, December 2019 saw the emergence of a potentially fatal coronavirus — SARS-CoV-2, which originated in Wuhan, China. While most coronaviruses are responsible for mild respiratory infections, they have been demonstrated to be neuroinvasive and neurotropic for over three decades. In this review, we assess whether SARS-CoV-2 follows this trend and if the neuroinvasive potential of this novel coronavirus is worthy of further investigation. Methods. To obtain sources for this study, we performed an online search through Pubmed, Researchgate and Google Scholar, finding 537 articles. After analysing them according to PRISMA, we included 14 in this review. Discussion. Data regarding neurological manifestations of SARS-CoV-2 is scarce and mostly inconsistent. There are however identifiable trends which might provide a basis for future research. There is strong evidence that this novel coronavirus may be neuroinvasive and could cause a wide array of neurological symptoms and complications. Cerebrospinal fluid testing may shed more light on the occurrence of SARS-CoV-2 in the central nervous system. Clarification of the respiratory failure mechanisms requires post mortem examinations and brain tissue analysis, and further research is of the utmost importance. However, we strongly believe that the existing evidence is enough to raise awareness among clinicians and help guide them through the diagnosis and optimal therapy of COVID-19 patients.

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References

  1. Su S, Wong G, Shi W, et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol. 2016; 24(6): 490–502.
  2. Corman VM, Lienau J, Witzenrath M. [Coronaviruses as the cause of respiratory infections]. Internist (Berl). 2019; 60(11): 1136–1145.
  3. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020; 109: 102433.
  4. World Health Organisation (WHO). Coronavirus disease 2019 (COVID-19) Situation Report – 144 [Internet]. WHO. 2020 . https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200612-covid-19-sitrep-144.pdf?sfvrsn=66ff9f4f_2 (2020 Jun 12).
  5. Desforges M, Le Coupanec A, Brison E, et al. Neuroinvasive and neurotropic human respiratory coronaviruses: potential neurovirulent agents in humans. Adv Exp Med Biol. 2014; 807: 75–96.
  6. Moher D, Liberati A, Tetzlaff J, et al. PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Open Med. 2009; 3(3): e123–e130.
  7. Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 [Epub ahead of print].
  8. Li Y, Li M, Wang M, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol. 2020 [Epub ahead of print].
  9. Helms J, Kremer S, Merdji H, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020; 382(23): 2268–2270.
  10. Yin R, Feng W, Wang T, et al. Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019. J Med Virol. 2020 [Epub ahead of print].
  11. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020; 94: 55–58.
  12. Poyiadji N, Shahin G, Noujaim D, et al. COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology. 2020 [Epub ahead of print]: 201187.
  13. Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020; 382(26): 2574–2576.
  14. Zhao H, Shen D, Zhou H, et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol. 2020; 19(5): 383–384.
  15. Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020 [Epub ahead of print].
  16. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223): 497–506.
  17. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020; 8(5): 475–481.
  18. Wang D, Hu Bo, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 [Epub ahead of print].
  19. 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.
  20. Du Y, Tu L, Zhu P, et al. Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study. Am J Respir Crit Care Med. 2020; 201(11): 1372–1379.
  21. Finsterer J, Stollberger C. Update on the neurology of COVID-19. J Med Virol. 2020 [Epub ahead of print].
  22. Desforges M, Le Coupanec A, Dubeau P, et al. Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? Viruses. 2019; 12(1).
  23. Arbour N, Day R, Newcombe J, et al. Neuroinvasion by human respiratory coronaviruses. J Virol. 2000; 74(19): 8913–8921.
  24. Arbour N, Côté G, Lachance C, et al. Acute and persistent infection of human neural cell lines by human coronavirus OC43. J Virol. 1999; 73(4): 3338–3350.
  25. Desforges M, Le Coupanec A, Dubeau P, et al. Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? Viruses. 2019; 12(1).
  26. Dubé M, Le Coupanec A, Wong AHM, et al. Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43. J Virol. 2018; 92(17).
  27. Hung ECW, Chim SSC, Chan PKS, 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.
  28. Algahtani H, Subahi A, Shirah B. Neurological Complications of Middle East Respiratory Syndrome Coronavirus: A Report of Two Cases and Review of the Literature. Case Rep Neurol Med. 2016; 2016: 3502683.
  29. Lau KK, Yu WC, Chu CM, et al. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis. 2004; 10(2): 342–344.
  30. Nath A. Neurologic complications of coronavirus infections. Neurology. 2020; 94(19): 809–810.
  31. Zhou L, Zhang M, Wang J, et al. Sars-Cov-2: Underestimated damage to nervous system. Travel Med Infect Dis. 2020 [Epub ahead of print]: 101642.
  32. Baig AM, Khaleeq A, Ali U, et al. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020; 11(7): 995–998.
  33. Netland J, Meyerholz DK, Moore S, et al. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008; 82(15): 7264–7275.
  34. Miller RW. There's a new symptom of coronavirus, doctors say: Sudden loss of smell or taste [Internet]. USA Today . https://eu.usatoday.com/story/news/health/2020/03/24/coronavirus-symptoms-loss-smell-taste/2897385001/ (2020 Mar 25).
  35. Giacomelli A, Pezzati L, Conti F, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis. 2020 [Epub ahead of print].
  36. Sun T, Guan J. Novel coronavirus and the central nervous system. Eur J Neurol. 2020 [Epub ahead of print].
  37. Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020; 87: 18–22.
  38. Wichmann D, Sperhake JP, Lütgehetmann M, et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19. Ann Intern Med. 2020 [Epub ahead of print].
  39. Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020; 382(17): e38.
  40. Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020; 46(5): 846–848.
  41. 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; 92(6): 552–555.
  42. Tsai LK, Hsieh ST, Chang YC. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwan. 2005; 14(3): 113–119.
  43. Hwang CS. Olfactory neuropathy in severe acute respiratory syndrome: report of A case. Acta Neurol Taiwan. 2006; 15(1): 26–28.
  44. Li YC, Bai WZ, Hashikawa T. Response to Commentary on "The neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients". J Med Virol. 2020; 92(7): 707–709.



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