Neuromuscular Complications of COVID-19: Evidence from the Third Year of the Global Pandemic

Abstract

Accumulating evidence in the third year of the global pandemic suggests that coronavirus disease 2019 (COVID-19) can cause neuromuscular complications during or after the acute phase of infection. Direct viral infection and immune-mediated mechanisms have been hypothesized. Furthermore, in patients with underlying autoimmune neuromuscular diseases, COVID-19 infection may trigger a disease flare. COVID-19 vaccines appear to be safe and effective at preventing severe illness from COVID-19. Certain vaccines are associated with an increased risk of Guillain-Barré syndrome and possibly Bell's palsy, but the absolute incidence is low, and benefits likely outweigh the risks. Newer prophylactic therapies and treatments are also becoming available for patients who may not mount a sufficient response to vaccination or have contraindications. In this article, we discuss the current available evidence on neuromuscular complications of COVID-19 and clinical considerations regarding vaccination.

Keywords

COVID-19 - SARS-CoV-2 - neuromuscular - Gullain-Barre syndrome - myasthenia - myositis - immune-mediated necrotizing myopathy

Publikationsverlauf

Artikel online veröffentlicht:
31. März 2023

• References

• 1 Araújo NM, Ferreira LC, Dantas DP. et al. First report of SARS-CoV-2 detection in cerebrospinal fluid in a child with Guillain-Barré syndrome. Pediatr Infect Dis J 2021; 40 (07) e274-e276
• 2 Gutiérrez-Ortiz C, Méndez-Guerrero A, Rodrigo-Rey S. et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19. Neurology 2020; 95 (05) e601-e605
• 3 Petrelli C, Scendoni R, Paglioriti M, Logullo FO. Acute motor axonal neuropathy related to COVID-19 infection: a new diagnostic overview. J Clin Neuromuscul Dis 2020; 22 (02) 120-121
• 4 Civardi C, Collini A, Geda DJ, Geda C. Antiganglioside antibodies in Guillain-Barré syndrome associated with SARS-CoV-2 infection. J Neurol Neurosurg Psychiatry 2020; 91 (12) 1361-1362
• 5 Dalakas MC. Guillain-Barré syndrome: the first documented COVID-19-triggered autoimmune neurologic disease: more to come with myositis in the offing. Neurol Neuroimmunol Neuroinflamm 2020; 7 (05) e781
• 6 Fantini J, Di Scala C, Chahinian H, Yahi N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicrob Agents 2020; 55 (05) 105960
• 7 Zhou P, Yang XL, Wang XG. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579 (7798): 270-273
• 8 Lu H, Yan P, Xiong W, Wang J, Liu X. Genomic characterization of a novel virulent phage infecting Shigella flexneri and isolated from sewage. Virus Res 2020; 283: 197983
• 9 Lucchese G, Flöel A. SARS-CoV-2 and Guillain-Barré syndrome: molecular mimicry with human heat shock proteins as potential pathogenic mechanism. Cell Stress Chaperones 2020; 25 (05) 731-735
• 10 Morsy S. NCAM protein and SARS-COV-2 surface proteins: in-silico hypothetical evidence for the immunopathogenesis of Guillain-Barré syndrome. Med Hypotheses 2020; 145: 110342
• 11 Keddie S, Pakpoor J, Mousele C. et al. Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome. Brain 2021; 144 (02) 682-693
• 12 Miró Ò, Llorens P, Jiménez S. et al; Spanish Investigators in Emergency Situations TeAm (SIESTA) network. Frequency of five unusual presentations in patients with COVID-19: results of the UMC-19-S₁ . Epidemiol Infect 2020; 148: e189
• 13 Patone M, Handunnetthi L, Saatci D. et al. Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nat Med 2021; 27 (12) 2144-2153
• 14 Luijten LWG, Leonhard SE, van der Eijk AA. et al; IGOS Consortium. Guillain-Barré syndrome after SARS-CoV-2 infection in an international prospective cohort study. Brain 2021; 144 (11) 3392-3404
• 15 Garnero M, Del Sette M, Assini A. et al. COVID-19-related and not related Guillain-Barré syndromes share the same management pitfalls during lock down: the experience of Liguria region in Italy. J Neurol Sci 2020; 418: 117114
• 16 Gigli GL, Bax F, Marini A. et al. Guillain-Barré syndrome in the COVID-19 era: just an occasional cluster?. J Neurol 2021; 268 (04) 1195-1197
• 17 Filosto M, Cotti Piccinelli S, Gazzina S. et al. Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions. J Neurol Neurosurg Psychiatry 2021; 92 (07) 751-756
• 18 Umapathi T, Er B, Koh JS, Goh YH, Chua L. Guillain-Barré syndrome decreases in Singapore during the COVID-19 pandemic. J Peripher Nerv Syst 2021; 26 (02) 235-236
• 19 Lunn MP, Carr AC, Keddie S, Pakpoor J, Pipis M, Willison HJ. Reply: Guillain-Barré syndrome, SARS-CoV-2 and molecular mimicry and Ongoing challenges in unravelling the association between COVID-19 and Guillain-Barré syndrome and Unclear association between COVID-19 and Guillain-Barré syndrome and currently available data regarding the potential association between COVID-19 and Guillain-Barré syndrome. Brain 2021; 144 (05) e47
• 20 Oaklander AL, Mills AJ, Kelley M. et al. Peripheral neuropathy evaluations of patients with prolonged long COVID. Neurol Neuroimmunol Neuroinflamm 2022; 9 (03) e1146
• 21 Scala I, Bellavia S, Luigetti M. et al. Autonomic dysfunction in non-critically ill COVID-19 patients during the acute phase of disease: an observational, cross-sectional study. Neurol Sci 2022; 43 (08) 4635-4643
• 22 Odozor CU, Kannampallil T, Ben Abdallah A. et al. Post-acute sensory neurological sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: the COVID-PN observational cohort study. Pain 2022; 163 (12) 2398-2410
• 23 Abrams RMC, Simpson DM, Navis A, Jette N, Zhou L, Shin SC. Small fiber neuropathy associated with SARS-CoV-2 infection. Muscle Nerve 2022; 65 (04) 440-443
• 24 Novak P, Mukerji SS, Alabsi HS. et al. Multisystem involvement in post-acute sequelae of coronavirus disease 19. Ann Neurol 2022; 91 (03) 367-379
• 25 Barizien N, Le Guen M, Russel S, Touche P, Huang F, Vallée A. Clinical characterization of dysautonomia in long COVID-19 patients. Sci Rep 2021; 11 (01) 14042
• 26 Shiers S, Ray PR, Wangzhou A. et al. ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects. Pain 2020; 161 (11) 2494-2501
• 27 Suh J, Mukerji SS, Collens SI. et al. Skeletal muscle and peripheral nerve histopathology in COVID-19. Neurology 2021; 97 (08) e849-e858
• 28 Márquez Loza AM, Holroyd KB, Johnson SA, Pilgrim DM, Amato AA. Guillain-Barré syndrome in the placebo and active arms of a COVID-19 vaccine clinical trial: temporal associations do not imply causality. Neurology 2021;
• 29 Woo EJ, Mba-Jonas A, Dimova RB, Alimchandani M, Zinderman CE, Nair N. Association of receipt of the Ad26.COV2.S COVID-19 vaccine with presumptive Guillain-Barré syndrome, February-July 2021. JAMA 2021; 326 (16) 1606-1613
• 30 Hanson KE, Goddard K, Lewis N. et al. Incidence of Guillain-Barré syndrome after COVID-19 vaccination in the Vaccine Safety Datalink. JAMA Netw Open 2022; 5 (04) e228879
• 31 Atzenhoffer M, Auffret M, Pegat A. et al. Guillain-Barré syndrome associated with COVID-19 vaccines: a perspective from spontaneous report data. Clin Drug Investig 2022; 42 (07) 581-592
• 32 Keh RYS, Scanlon S, Datta-Nemdharry P. et al; BPNS/ABN COVID-19 Vaccine GBS Study Group. COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database. Brain 2023; 146 (02) 739-748
• 33 Maramattom BV, Krishnan P, Paul R. et al. Guillain-Barré syndrome following ChAdOx1-S/nCoV-19 vaccine. Ann Neurol 2021; 90 (02) 312-314
• 34 Osowicki J, Morgan H, Harris A, Crawford NW, Buttery JP, Kiers L. Guillain-Barré syndrome in an Australian state using both mRNA and adenovirus-vector SARS-CoV-2 vaccines. Ann Neurol 2021; 90 (05) 856-858
• 35 Rosenblum HG, Hadler SC, Moulia D. et al. Use of COVID-19 vaccines after reports of adverse events among adult recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna): update from the Advisory Committee on Immunization Practices - United States, July 2021. MMWR Morb Mortal Wkly Rep 2021; 70 (32) 1094-1099
• 36 COVID-19 Vaccine Safety Update. Vaxzevria AstraZeneca AB. European Medicines Agency. Updated September 2021. Accessed August 30, 2022 at: https://www.ema.europa.eu/en/documents/covid-19-vaccine-safety-update/covid-19-vaccine-safety-update-vaxzevria-previously-covid-19-vaccine-astrazeneca-8-september-2021_en.pdf
• 37 COVID-19 Vaccine Safety Update. COVID-19 vaccine Janssen. European Medicines Agency. Updated August 11, 2021. Accessed August 30, 2022 at: https://www.ema.europa.eu/en/documents/covid-19-vaccine-safety-update/covid-19-vaccine-safety-update-covid-19-vaccine-janssen-11-august-2021_en.pdf
• 38 Vaccine Considerations for People Who Are Moderately or Severely Immunocompromised. Centers for Disease Control and Prevention. Updated September 2, 2022. Accessed September 2, 2022 at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html#:∼:text=If%20you%20are%20moderately%20or%20severely%20immunocompromised%20or%20severely%20allergic,you%20from%20getting%20COVID%2D19
• 39 Shapiro Ben David S, Potasman I, Rahamim-Cohen D. Rate of recurrent Guillain-Barré syndrome after mRNA COVID-19 vaccine BNT162b2. JAMA Neurol 2021; 78 (11) 1409-1411
• 40 Wan EYF, Chui CSL, Lai FTT. et al. Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study. Lancet Infect Dis 2022; 22 (01) 64-72
• 41 Ozonoff A, Nanishi E, Levy O. Bell's palsy and SARS-CoV-2 vaccines-an unfolding story - authors' reply. Lancet Infect Dis 2021; 21 (09) 1211-1212
• 42 Sato K, Mano T, Niimi Y, Toda T, Iwata A, Iwatsubo T. Facial nerve palsy following the administration of COVID-19 mRNA vaccines: analysis of a self-reporting database. Int J Infect Dis 2021; 111: 310-312
• 43 Shemer A, Pras E, Einan-Lifshitz A, Dubinsky-Pertzov B, Hecht I. Association of COVID-19 vaccination and facial nerve palsy: a case-control study. JAMA Otolaryngol Head Neck Surg 2021; 147 (08) 739-743
• 44 Shasha D, Bareket R, Sikron FH. et al. Real-world safety data for the Pfizer BNT162b2 SARS-CoV-2 vaccine: historical cohort study. Clin Microbiol Infect 2022; 28 (01) 130-134
• 45 Renoud L, Khouri C, Revol B. et al. Association of facial paralysis with mRNA COVID-19 vaccines: a disproportionality analysis using the World Health Organization Pharmacovigilance Database. JAMA Intern Med 2021; 181 (09) 1243-1245
• 46 Gummi RR, Kukulka NA, Deroche CB, Govindarajan R. Factors associated with acute exacerbations of myasthenia gravis. Muscle Nerve 2019; 60 (06) 693-699
• 47 Businaro P, Vaghi G, Marchioni E. et al. COVID-19 in patients with myasthenia gravis: epidemiology and disease course. Muscle Nerve 2021; 64 (02) 206-211
• 48 Solé G, Mathis S, Friedman D. et al. Impact of coronavirus disease 2019 in a French cohort of myasthenia gravis. Neurology 2021; 96 (16) e2109-e2120
• 49 Roy B, Kovvuru S, Nalleballe K, Onteddu SR, Nowak RJ. Electronic health record derived-impact of COVID-19 on myasthenia gravis. J Neurol Sci 2021; 423: 117362
• 50 Kim Y, Li X, Huang Y. et al. COVID-19 outcomes in myasthenia gravis patients: analysis from electronic health records in the United States. Front Neurol 2022; 13: 802559
• 51 Muppidi S, Guptill JT, Jacob S. et al; CARE-MG Study Group. COVID-19-associated risks and effects in myasthenia gravis (CARE-MG). Lancet Neurol 2020; 19 (12) 970-971
• 52 Jakubíková M, Týblová M, Tesař A. et al. Predictive factors for a severe course of COVID-19 infection in myasthenia gravis patients with an overall impact on myasthenic outcome status and survival. Eur J Neurol 2021; 28 (10) 3418-3425
• 53 Felten R, Duret PM, Bauer E. et al. B-cell targeted therapy is associated with severe COVID-19 among patients with inflammatory arthritides: a 1-year multicentre study in 1116 successive patients receiving intravenous biologics. Ann Rheum Dis 2022; 81 (01) 143-145
• 54 Simpson AI, Vaghela KR, Brown H. et al. Reducing the risk and impact of brachial plexus injury sustained from prone positioning - a clinical commentary. J Intensive Care Med 2020; 35 (12) 1576-1582
• 55 Salter A, Fox RJ, Newsome SD. et al. Outcomes and risk factors associated with SARS-CoV-2 infection in a North American Registry of patients with multiple sclerosis. JAMA Neurol 2021; 78 (06) 699-708
• 56 Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: a systematic review and meta-analysis. EClinicalMedicine 2020; 29: 100639
• 57 Hoang P, Hurtubise B, Muppidi S. Clinical reasoning: therapeutic considerations in myasthenic crisis due to COVID-19 infection. Neurology 2020; 95 (18) 840-843
• 58 Stahl K, Bode C, David S. First do no harm-beware the risk of therapeutic plasma exchange in severe COVID-19. Crit Care 2020; 24 (01) 363
• 59 Jacob S, Muppidi S, Guidon A. et al; International MG/COVID-19 Working Group. Guidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic. J Neurol Sci 2020; 412: 116803
• 60 Živković SA, Gruener G, Narayanaswami P. AANEM Quality and Patient Safety Committee. Doctor-Should I get the COVID-19 vaccine? Infection and immunization in individuals with neuromuscular disorders. Muscle Nerve 2021; 63 (03) 294-303
• 61 Farina A, Falso S, Cornacchini S. et al. Safety and tolerability of SARS-CoV-2 vaccination in patients with myasthenia gravis: a multicenter experience. Eur J Neurol 2022; 29 (08) 2505-2510
• 62 Ishizuchi K, Takizawa T, Sekiguchi K. et al. Flare of myasthenia gravis induced by COVID-19 vaccines. J Neurol Sci 2022; 436: 120225
• 63 Lotan I, Hellmann MA, Friedman Y, Stiebel-Kalish H, Steiner I, Wilf-Yarkoni A. Early safety and tolerability profile of the BNT162b2 COVID-19 vaccine in myasthenia gravis. Neuromuscul Disord 2022; 32 (03) 230-235
• 64 Reyes-Leiva D, López-Contreras J, Moga E. et al. Immune response and safety of SARS-CoV-2 mRNA-1273 vaccine in patients with myasthenia gravis. Neurol Neuroimmunol Neuroinflamm 2022;9(4):e200002
• 65 Fact Sheet for Patients, Parents and Caregivers. Emergency Use Authorization (EUA) of EVUSHELD™ (tixagevimab co-packaged with cilgavimab) for Coronavirus Disease 2019 (COVID-19). AstraZeneca. Accessed March 5, 2023 at: https://www.fda.gov/media/154702/download
• 66 Ruddy JA, Connolly CM, Boyarsky BJ. et al. High antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with rheumatic and musculoskeletal diseases. Ann Rheum Dis 2021; 80 (10) 1351-1352
• 67 Bitoun S, Avouac J, Henry J. et al. Very low rate of humoral response after a third COVID-19 vaccine dose in patients with autoimmune diseases treated with rituximab and non-responders to two doses. RMD Open 2022; 8 (01) 8
• 68 Jyssum I, Kared H, Tran TT. et al. Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study. Lancet Rheumatol 2022; 4 (03) e177-e187
• 69 Fact Sheet for Patients, Parents, and Caregivers. Emergency Use Authorization (EUA) of Paxlovid for Coronavirus Disease 2019 (COVID-19). Pfizer Labs. Updated August 26, 2022. Accessed August 30, 2022 at: https://www.fda.gov/media/155051/download
• 70 Romero-Sánchez CM, Díaz-Maroto I, Fernández-Díaz E. et al. Neurologic manifestations in hospitalized patients with COVID-19: the ALBACOVID registry. Neurology 2020; 95 (08) e1060-e1070
• 71 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
• 72 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
• 73 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 (06) 577-583
• 74 Borges do Nascimento IJ, Cacic N, Abdulazeem HM. et al. Novel coronavirus infection (COVID-19) in humans: a scoping review and meta-analysis. J Clin Med 2020; 9 (04) 9
• 75 Wang D, Hu B, Hu C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323 (11) 1061-1069
• 76 Mao L, Jin H, Wang M. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; 77 (06) 683-690
• 77 Guan WJ, Ni ZY, Hu Y. et al; China Medical Treatment Expert Group for COVID-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720
• 78 Geng Y, Ma Q, Du YS. et al. Rhabdomyolysis is associated with in-hospital mortality in patients with COVID-19. Shock 2021; 56 (03) 360-367
• 79 Haroun MW, Dieiev V, Kang J. et al. Rhabdomyolysis in COVID-19 patients: a retrospective observational study. Cureus 2021; 13 (01) e12552
• 80 Manzano GS, Woods JK, Amato AA. COVID-19-associated myopathy caused by Type I interferonopathy. N Engl J Med 2020; 383 (24) 2389-2390
• 81 Zhang H, Charmchi Z, Seidman RJ, Anziska Y, Velayudhan V, Perk J. COVID-19-associated myositis with severe proximal and bulbar weakness. Muscle Nerve 2020; 62 (03) E57-E60
• 82 Tanboon J, Nishino I. COVID-19-associated myositis may be dermatomyositis. Muscle Nerve 2021; 63 (01) E9-E10
• 83 Okada Y, Izumi R, Hosaka T. et al. Anti-NXP2 antibody-positive dermatomyositis developed after COVID-19 manifesting as type I interferonopathy. Rheumatology (Oxford) 2022; 61 (04) e90-e92
• 84 Aschman T, Schneider J, Greuel S. et al. Association between SARS-CoV-2 infection and immune-mediated myopathy in patients who have died. JAMA Neurol 2021; 78 (08) 948-960
• 85 Shi Z, de Vries HJ, Vlaar APJ. et al; Dutch COVID-19 Diaphragm Investigators. Diaphragm pathology in critically ill patients with COVID-19 and postmortem findings from 3 medical centers. JAMA Intern Med 2021; 181 (01) 122-124
• 86 Hooper JE, Uner M, Priemer DS, Rosenberg A, Chen L. Muscle biopsy findings in a case of SARS-CoV-2-associated muscle injury. J Neuropathol Exp Neurol 2021; 80 (04) 377-378
• 87 Dodig D, Tarnopolsky MA, Margeta M, Gordon K, Fritzler MJ, Lu JQ. COVID-19-associated critical illness myopathy with direct viral effects. Ann Neurol 2022; 91 (04) 568-574
• 88 Rodriguez B, Branca M, Gutt-Will M. et al. Development and early diagnosis of critical illness myopathy in COVID-19 associated acute respiratory distress syndrome. J Cachexia Sarcopenia Muscle 2022; 13 (03) 1883-1895
• 89 Frithiof R, Rostami E, Kumlien E. et al. Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: a prospective study. Clin Neurophysiol 2021; 132 (07) 1733-1740
• 90 Tankisi H, Tankisi A, Harbo T, Markvardsen LK, Andersen H, Pedersen TH. Critical illness myopathy as a consequence of COVID-19 infection. Clin Neurophysiol 2020; 131 (08) 1931-1932
• 91 Gil-Vila A, Ravichandran N, Selva-O'Callaghan A. et al; COVAD Study Group. COVID-19 Vaccination in Autoimmune Diseases (COVAD) study: vaccine safety in idiopathic inflammatory myopathies. Muscle Nerve 2022; 66 (04) 426-437
• 92 Connolly CM, Ruddy JA, Boyarsky BJ. et al. Disease flare and reactogenicity in patients with rheumatic and musculoskeletal diseases following two-dose SARS-CoV-2 messenger RNA vaccination. Arthritis Rheumatol 2022; 74 (01) 28-32
• 93 Conticini E, d'Alessandro M, Grazzini S. et al. Relapses of idiopathic inflammatory myopathies after vaccination against COVID-19: a real-life multicenter Italian study. Intern Emerg Med 2022; 17 (07) 1921-1928