Neurological manifestations and complications in patients with covid-19

It becomes apparent that the neurological complications of COVID-19 are significantly common, but in some cases, establishing a causal relationship is difficult. For example, a stroke can occur for reasons unrelated to coronavirus infection, while Guillain–Barré syndrome and meningoencephalitis are likely to be a parainfection. Only long-term epidemiological studies in large groups of patients can clarify some of these issues. This will help to better understand the mechanisms of development of complications and develop schemes for their treatment and subsequent rehabilitation. The article presents the mechanisms of penetration of the coronavirus into the nervous system and systematizes the neurological manifestations and complications of COVID-19, which were described in the first 3 months of the pandemic. Particular attention is paid to the consideration of the complications of COVID-19 from the central and peripheral nervous system, the most interesting clinical examples are considered. Summing up the analysis of the literature, we can say that the clinical picture of neurological diseases and syndromes caused by coronavirus infection corresponds to the usual notions. Also considered is the assumption that SARS-CoV-2 can persist for a long time in the central nervous system in the form of inactive fragments, which means that it can recur in predisposed individuals when appropriate conditions arise. This suggestion is alarming regarding distant neurological complications in infected and cured patients.

acute myelitis, COVID-19, encephalitis, Guillain–Barré syndrome, stroke, neurological complications of COVID-19

1. Временные методические рекомендации Минздрава России «Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Москва, 2020. Версия 7 (03.06.2020)». Available from: https://static0.rosminzdrav.ru/system/attachments/attaches/000/050/584/original/03062020_%D0%9CR_COVID-19_v7.pdf. [Temporary methodological recommendations of Ministry of health of Russia “Prevention, diagnosis and treatment of the new coronavirus infection (COVID-19). Moscow, 2020. Version 7(03.06.2020)”. Available from: https://static0.rosminzdrav.ru/system/attachments/attaches/000/050/584/original/03062020_%D0%9CR_COVID-19_v7.pdf. In Russian].

2. Baig AM, Khaleeq A, Ali U, et al. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, hostvirus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020;11(7):995–998.

3. Palasca O, Santos A, Stolte C, et al. TISSUES 2.0: an integrative web resource on mammalian tissue expression [published correction appears in Database (Oxford). 2018 Jan 1;2018]. Database (Oxford). 2018;2018:bay003.

4. Li Y, Li H, Fan R, et al. Coronavirus infections in the central nervous system and respiratory tract show distinct features in hospitalized children. Intervirology. 2016;59(3):163–169.

5. Niu J, Shen L, Huang B, et al. Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice. Antiviral Res. 2020;173:104646.

6. Li K, Wohlford-Lenane C, Perlman S, 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(5):712–722.

7. 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.

8. Chan JF, Chan KH, Choi GK, et al. Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications for disease pathogenesis and clinical manifestation. J Infect Dis. 2013;207(11):1743–1752.

9. Desforges M, Miletti TC, Gagnon M, et al. Activation of human monocytes after infection by human coronavirus 229E. Virus Res. 2007;130(1–2):228–240.

10. Li J, Gao J, Xu YP, et al. [Expression of severe acute respiratory syndrome coronavirus receptors, ACE2 and CD209L in different organ derived microvascular endothelial cells]. Zhonghua Yi Xue Za Zhi. 2007;87(12):833–837.

11. Li YC, Bai WZ, Hirano N, et al. Neurotropic virus tracing suggests a membranous-coating-mediated mechanism for transsynaptic communication. J Comp Neurol. 2013;521(1):203–212.

12. Benussi A, Pilotto A, Premi E, et al. Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy [published online ahead of print, 2020 May 22]. Neurology. 2020;10.1212/WNL.0000000000009848.

13. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China [published online ahead of print, 2020 Apr 10]. JAMA Neurol. 2020;77(6):1–9.

14. 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.

15. Deng Y, Liu W, Liu K, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. Chin Med J (Engl). 2020;133(11):1261–1267.

16. Li LQ, Huang T, Wang YQ, et al. COVID-19 patients’ clinical characteristics, discharge rate, and fatality rate of meta-analysis. J Med Virol. 2020;92(6):577–583.

17. González-Pinto T, Luna-Rodríguez A, Moreno- Estébanez A, et al. Emergency room neurology in times of COVID-19: malignant ischaemic stroke and SARS-CoV-2 infection [published online ahead of print, 2020 Apr 30]. Eur J Neurol. 2020;10.1111/ene.14286.

18. Beyrouti R, Adams ME, Benjamin L, et al. Characteristics of ischaemic stroke associated with COVID-19 [published online ahead of print, 2020 Apr 30]. J Neurol Neurosurg Psychiatry. 2020;jnnp-2020-323586.

19. Al Saiegh F, Ghosh R, Leibold A, et al. Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke [published online ahead of print, 2020 Apr 30]. J Neurol Neurosurg Psychiatry. 2020;jnnp-2020-323522.

20. Oxley TJ, Mocco J, Majidi S, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020;382(20):e60.

21. 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.

22. Lushina N, Kuo JS, Shaikh HA. Pulmonary, Cerebral, and Renal Thromboembolic Disease Associated with COVID-19 Infection [published online ahead of print, 2020 Apr 23]. Radiology. 2020;201623.

23. Zhai P, Ding Y, Li Y. The impact of COVID-19 on ischemic stroke: a case report. Res Sq. 2020.

24. Sharifi-Razavi A, Karimi N, Rouhani N. COVID-19 and intracerebral haemorrhage: causative or coincidental? New Microbes New Infect. 2020;35:100669.

25. Moshayedi P, Ryan TE, Mejia LLP, et al. Triage of acute ischemic stroke in confirmed COVID-19: large vessel occlusion associated with coronavirus infection. Front Neurol. 2020;11:353.

26. Li Y. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. SSRN Electron J. 2020.

27. Lodigiani C, Iapichino G, Carenzo L, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9–14.

28. 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.

29. Filatov A, Sharma P, Hindi F, et al. Neurological complications of coronavirus disease (COVID-19): Encephalopathy. Cureus. 2020;12(3):e7352.

30. Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study [published correction appears in BMJ. 2020 Mar 31;368:m1295]. BMJ. 2020;368:m1091.

31. Poyiadji N, Shahin G, Noujaim D, et al. COVID-19- associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features [published online ahead of print, 2020 Mar 31]. Radiology. 2020;201187.

32. Zhou L, Zhang M, Wang J, et al. Sars-CoV-2: Underestimated damage to nervous system [published online ahead of print, 2020 Mar 24]. Travel Med Infect Dis. 2020;101642.

33. Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19 [published online ahead of print, 2020 Apr 10]. Brain Behav Immun. 2020;S0889-1591(20)30465-7.

34. Pilotto A, Odolini S, Masciocchi S, et al. Steroidresponsive encephalitis in coronavirus disease 2019 [published online ahead of print, 2020 May 17]. Ann Neurol. 2020;10.1002/ana.25783.

35. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARSCoronavirus-2. Int J Infect Dis. 2020;94:55–58.

36. Duong L, Xu P, Liu A. Meningoencephalitis without respiratory failure in a young female patient with COVID-19 infection in Downtown Los Angeles, early April 2020. Brain Behav Immun. 2020;87:33.

37. Bernard-Valnet R, Pizzarotti B, Anichini A, et al. Two patients with acute meningo-encephalitis concomitant to SARS-CoV-2 infection. medRxiv 2020.

38. Zhao K, Huang J, Dai D, et al. Acute myelitis after SARS-CoV-2 infection: a case report. medRxiv 2020.

39. Yan CH, Faraji F, Prajapati DP, et al. Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms [published online ahead of print, 2020 Apr 12]. Int Forum Allergy Rhinol. 2020;10.1002/alr.22579.

40. Bagheri SH, Asghari AM, Farhadi M, et al. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak. medRxiv 2020.

41. Alberti P, Beretta S, Piatti M, et al. Guillain-Barré syndrome related to COVID-19 infection. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e741.

42. Padroni M, Mastrangelo V, Asioli GM, et al. Guillain-Barré syndrome following COVID-19: new infection, old complication? [published online ahead of print, 2020 Apr 24]. J Neurol. 2020;1–3.

43. Virani A, Rabold E, Hanson T, et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection [published online ahead of print, 2020 Apr 18]. IDCases. 2020;20:e00771.

44. Camdessanche JP, Morel J, Pozzetto B, et al. COVID-19 may induce Guillain-Barré syndrome. Rev Neurol (Paris). 2020;176(6):516–518.

45. Sedaghat Z, Karimi N. Guillain Barre syndrome associated with COVID-19 infection: A case report. J Clin Neurosci. 2020;76:233–235.

46. 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.

47. 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.

48. Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19 [published online ahead of print, 2020 Apr 17]. Neurology. 2020;10.1212/WNL.0000000000009619.

49. Jacomy H, Fragoso G, Almazan G, et al. Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice. Virology. 2006;349(2):335–346.