J Clin Neurol. 2022 Jan;18(1):1-2. English.
Published online Dec 30, 2021.
Copyright © 2022 Korean Neurological Association
Editorial

Lessons from COVID-19 in Clinical Neurology

Jin-Woo Park,a and Byung-Jo Kima,b
    • aDepartment of Neurology, Korea University Anam Hospital, Korea University Medicine, Seoul, Korea.
    • bBK21 FOUR Program in Learning Health Systems, Korea University, Seoul, Korea.
Received December 03, 2021; Revised December 14, 2021; Accepted December 14, 2021.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

COVID-19 has had a considerable impact on society. One negative impact of this disease is the neurological dysfunctions that can result from SARS-CoV-2 infection, in addition to respiratory problems. One in 20 patients with COVID-19 complains of neurological complications,1 but whether COVID-19 provokes or triggers neurological problems remains unclear. There is a need for thorough research into the correlation between COVID-19 and neurological disorders. Before feasible research methods are set up, the only way to evaluate the causal relationship would be to carefully examine the temporal relationships between COVID-19 infection and neurological complications based on the accumulated clinical data. Since the COVID-19 outbreak, the Journal of Clinical Neurology (JCN) has published several reports related to COVID-19, including two original articles.

The first report in JCN was a case report of recurrent transient ischemic attack in a 47-year-old male with COVID-19 who did not have risk factors related to stroke.2 He experienced transient symptoms with left-side weakness and amaurosis fugax at 5 days after being admitted to hospital due to COVID-19. Another case report was also a patient with ischemic stroke associated with endocarditis of unknown origin after COVID-19.3 There have been increasing concerns regarding acute stroke related to COVID-19. Although this association remains controversial, clinical evidence for it is accumulating. A meta-analysis suggested a relatively high mortality rate and a considerable number of antiphospholipid-antibody-positive cases in acute ischemic stroke patients with COVID-19 infection.4 A review article introduced angiotensin-converting enzyme-2 (ACE2) downregulation as a possible pathomechanism of COVID-19-related acute ischemic stroke, which may augment the vasoconstrictor effect of angiotensin II and eliminate the protective role of ACE2 in the cardiovascular and cerebrovascular systems. It is particularly interesting that the surface spike protein on the SARS-CoV-2 virus may bind to ACE2 receptors on platelets, triggering their activation and aggregation, which may play a harmful role in ischemic stroke. Although the incidence of stroke is not particularly high in COVID-19 patients, clinicians should be aware of this possibility.

In addition to its pathological effects, COVID-19 also significantly impacts the healthcare system. The process and outcomes of recanalization therapy for ischemic stroke changed during the COVID-19 era in the Republic of Korea,5 because of prehospital delays and decreased opportunities for adequate rehabilitation before and after recanalization therapy. This is probably due to patients being more reluctant to visit a hospital, the presence of many safety processes for COVID-19 protection, and the reduced capacity of hospitals due to large numbers of COVID-19 patients. Indeed, the abrupt increase in patient numbers and the inability to accept critical patients in facilities have been serious problems during the pandemic, especially in undeveloped countries.6

Neurological manifestations in patients with COVID-19 admitted to the Central Infectious Diseases Hospital are summarized in another article. Neurological symptoms were present in 186 of 331 patients admitted from March 2020 to September 2020.7 Those authors found that stroke, seizure, and altered consciousness were significantly associated with the severity of COVID-19.

Healthcare professionals should be aware of unusual neurological manifestations of COVID-19. Acute confusion could be the initial manifestation of SARS-CoV-2 infection, especially in elderly patients. Direct neuroinvasion of the virus and systemic inflammatory processes may play a role in acute confusion.8 In another review of both large-scale studies and case reports of COVID-19-associated encephalitis and encephalopathy, the authors found that patients with encephalopathy/encephalitis were generally severely or critically ill, with almost all patients having lung abnormalities.9 Some patients presented with the SARS-CoV-2 virus in their cerebrospinal fluid.9 ACE2-related cell entry and central nervous system invasion, cytokine storm, coagulopathy, hypoxia, and molecular mimicry have all been suggested as possible culprits.

Guillain-Barré syndrome (GBS) is a relatively uncommon but profound neurological manifestation of COVID-19. A large cohort study found 6 cases of GBS among 10,881 new-onset neurological complications associated with COVID-19.1 The reported prevalence (approximately 0.06%) was higher than that observed in the general population (typically 0.001% to 0.004%). A case report also described a patient with facial diplegia, which occurred 2 weeks after SARS-CoV-2 infection.10 GBS has also been reported after COVID-19 vaccination. In a review of 73 cases of GBS associated with COVID-19, the authors found that features were similar to classic postinfectious GBS, and suggested that they share the same immune-mediated pathogenic mechanisms.11 In contrast, a systemic review of 11 cases of Miller Fisher syndrome (MFS) found that different targets and mechanisms might be associated with MFS when COVID-19 precedes this syndrome, considering the relatively uncommon presence of antiganglioside antibodies in patients.12

Lastly, JCN has published two case reports on COVID-19 vaccination-related neurological complications: 1) a rare case of vaccine-induced immune thrombotic thrombocytopenia13 and 2) a possible case of COVID-19-vaccination-related cerebral venous sinus thrombosis.14 The authors were only able to find a temporal relationship to explain this phenomenon. Vaccination-related neurological adverse events are tending to increase with the continuous increase of the vaccinated population. The great difficulty of demonstrating a direct causal relationship between vaccination and neurological complications makes it necessary to develop clinically useful biomarkers.

The COVID-19 pandemic has brought about a new era in healthcare. As our knowledge of the pandemic continues to evolve, the ongoing improvements in the methods for identifying neurological manifestations of COVID-19 will help us to develop effective healthcare strategies for dealing with new viruses.

Notes

Author Contributions:

  • Conceptualization: Byung-Jo Kim.

  • Writing—original draft: Jin-Woo Park, Byung-Jo Kim.

  • Writing—review & editing: Jin-Woo Park, Byung-Jo Kim.

Conflicts of Interest:The authors have no potential conflicts of interest to disclose.

Funding Statement:None

References

    1. Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. Philippine CORONA Study Group Investigators. COVID-19 outcomes of 10,881 patients: retrospective study of neurological symptoms and associated manifestations (Philippine CORONA Study). J Neural Transm (Vienna) 2021;128:1687–1703.
    1. Mantero V, Basilico P, Costantino G, Pozzetti U, Rigamonti A, Salmaggi A. Recurrent transient ischemic attack in a young patient with COVID-19. J Clin Neurol 2020;16:513–514.
    1. Mantero V, Rigamonti A, Basilico P, Sangalli D, Scaccabarozzi C, Salmaggi A. Stroke in a feverish patient with COVID-19 infection and unknown endocarditis. J Clin Neurol 2020;16:707–708.
    1. Taha M, Samavati L. Antiphospholipid antibodies in COVID-19: a meta-analysis and systematic review. RMD Open 2021;7:e001580
    1. Kim YD, Nam HS, Sohn SI, Park H, Hong JH, Kim GS, et al. Care process of recanalization therapy for acute stroke during the COVID-19 outbreak in South Korea. J Clin Neurol 2021;17:63–69.
    1. Soni A, Garg SK, Gupta R, Gupta P, Kansay R, Singhal A. Epidemiologic characteristics and pre-hospital care of traumatic injuries during the COVID-19 pandemic in an emerging and developing country: a single tertiary centre experience. J Clin Orthop Trauma 2021;23:101654
    1. Kim HK, Cho YJ, Lee SY. Neurological manifestations in patients with COVID-19: experiences from the Central Infectious Diseases Hospital in South Korea. J Clin Neurol 2021;17:435–442.
    1. Butt I, Ochoa-Ferraro A, Dawson C, Madathil S, Gautam N, Sawlani V, et al. Acute confusion as an initial presentation of SARS-CoV-2 infection. J Clin Neurol 2021;17:363–367.
    1. Garg RK, Paliwal VK, Gupta A. Encephalopathy in patients with COVID-19: a review. J Med Virol 2021;93:206–222.
    1. Yang HB, Lee HS. Facial diplegia: a rare subtype of Guillain-Barré syndrome in a patient with minimally symptomatic COVID-19. J Clin Neurol 2021;17:590–592.
    1. Abu-Rumeileh S, Abdelhak A, Foschi M, Tumani H, Otto M. Guillain-Barré syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases. J Neurol 2021;268:1133–1170.
    1. Martins-Filho PR, Pereira de Andrade AL, Pereira de Andrade AJ, Moura da Silva MD, de Souza Araújo AA, Nunes PS, et al. Miller Fisher syndrome in patients with severe acute respiratory syndrome coronavirus 2 infection: a systematic review. J Clin Neurol 2021;17:541–545.
    1. Kim MK, Jang S, Na SH, Bang SM, Kim JH. Vaccine-induced immune thrombotic thrombocytopenia: first case report in South Korea. J Clin Neurol 2021;17:570–572.
    1. Cheng N. Cerebral venous sinus thrombosis after Pfizer-BioNTech COVID-19 (BNT162b2) vaccination. J Clin Neurol 2021;17:573–575.

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