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Peripheral neuropathy in COVID-19 is due to immune-mechanisms, pre-existing risk factors, anti-viral drugs, or bedding in the Intensive Care Unit

Neuropatia periférica na COVID-19 com mecanismos immunológicos, fatores de risco preexistentes, medicamentos antivirais e compressão dos nervos periféricos nos leitos da Unidade de Terapia Intensiva

ABSTRACT

Background:

This mini-review aims to summarize and discuss previous and recent advances in the clinical presentation, pathophysiology, diagnosis, treatment, and outcome of SARS-CoV-2-associated peripheral neuropathies.

Methods:

Literature review.

Results:

Altogether, 105 articles about SARS-CoV-2-associated neuropathy describing 261 patients were retrieved. Peripheral neuropathy in patients with COVID-19 is frequent and predominantly due to immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, due to the compression of peripheral nerves resulting from prolonged bedding in the Intensive Care Unit (ICU) and pre-existing risk factors such as diabetes. SARS-CoV-2 does not cause viral neuropathy. Neurotoxic drugs such as daptomycin, linezolid, lopinavir, ritonavir, hydro-chloroquine, cisatracurium, clindamycin, and glucocorticoids should be administered with caution and patients should be appropriately bedded in the ICU to prevent SARS-CoV-2-associated neuropathy. Patients with Guillain-Barré syndrome (GBS) benefit from immunoglobulins, plasma exchange, and steroids.

Conclusions:

Neuropathies of peripheral nerves in patients with COVID-19 are frequent and mostly result from immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, from the compression of peripheral nerves due to prolonged bedding on the ICU. SARS-CoV-2 does not cause infectious neuropathy.

Keywords:
Guillain-Barre Syndrome; Polyneuropathies; Drug-Related Side Effects and Adverse Reactions; Mononeuritis Multiplex; SARS-CoV-2

RESUMO

Introdução:

A presente minirrevisão tem como objetivo resumir e discutir os avanços dos aspectos clínicos, fisiopatológicos, de diagnóstico, tratamento e evolução das neuropatias dos nervos periféricos associadas à COVID-19.

Métodos:

Revisão da literatura.

Resultados:

Foram avaliados 105 artigos sobre neuropatia associada à COVID-19. Nesses estudos, 261 pacientes apresentaram boa evolução. As neuropatias dos nervos periféricos em pacientes com COVID-19 são frequentes e se devem, principalmente, aos mecanismos immunológicos ou efeitos colaterais neurotóxicos dos medicamentos utilizados para o tratamento da COVID-19, a fatores de risco pré-existentes, como diabetes e, em menor parte, à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia viral. Os medicamentos neurotóxicos, como daptomicina, linezolida, lopinavir, ritonavir, hidro-cloroquina, cisatracúrio, clindamicina e glicocorticoides devem ser administrados com cautela, e os pacientes deve ser adequadamente admitidos nos leitos da UTI para prevenir o desenvolvimento de neuropatia associada à COVID-19. Pacientes com síndrome de Guillain-Barré (GBS) se beneficiam de imunoglobulinas, plasmaférese e esteroides.

Conclusões:

As neuropatias dos nervos periféricos em pacientes com COVID-19 são raras e predominantemente devidas aos efeitos colaterais neurotóxicos das mecanismos immunológicos ou drogas utilizadas para o tratamento de COVID-19 e, em menor parte, devido à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia infeciosa.

Palavras-chave:
Síndrome de Guillain-Barré; Polineuropatias; Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos; Mononeuropatias; SARS-CoV-2

INTRODUCTION

Infection with SARS-CoV-2 (COVID-19) causes not only pneumonia, but also neurological, cardiac, renal, hepatic, pancreatic, and gastrointestinal compromise11. Bal A, Agrawal R, Vaideeswar P, Arava S, Jain A. COVID-19: An up-to-date review - from morphology to pathogenesis. Indian J Pathol Microbiol. 2020 Jul-Sep;63(3):358-66. https://doi.org/10.4103/IJPM.IJPM_779_20
https://doi.org/https://doi.org/10.4103/...
,22. da Rosa Mesquita R, Francelino Silva Junior LC, Santos Santana FM, Farias de Oliveira T, Campos Alcântara R, Monteiro Arnozo G, et al. Clinical manifestations of COVID-19 in the general population: systematic review. Wien Klin Wochenschr. 2020 Nov:1-6. https://doi.org/10.1007/s00508-020-01760-4.
https://doi.org/https://doi.org/10.1007/...
. Neurological involvement following the infection has been increasingly acknowledged and includes impairment not only of the central nervous system (CNS), but also of the peripheral nervous system (PNS)33. Maramattom BV, Bhattacharjee S. Neurological Complications with COVID-19: A Contemporaneous Review. Ann Indian Acad Neurol. 2020 Jul-Aug;23(4):468-76. https://doi.org/10.4103/aian.AIAN_596_20
https://doi.org/https://doi.org/10.4103/...
, SARS-CoV-2-associated PNS disease includes rhabdomyolysis, myopathy, myositis, myasthenia, myasthenic syndrome, polyradiculitis with or without involvement of cranial nerves, and peripheral neuropathy. This mini-review aims to summarize and discuss previous and recent advances in the clinical presentation, pathophysiology, diagnosis, treatment, and outcome of SARS-CoV-2-associated peripheral neuropathy.

METHODS

A literature review after a search on the database PubMed using the terms “neuropathy”, “peripheral nerves”, “polyneuropathy”, “polyardiculitis”, “Guillain-Barré syndrome”, “polyradiculoneuritis”, and “nerves” along with “SARS-CoV-2”, “COVID-19”, and “coronavirus”. Additionally, reference lists were checked for further articles meeting the search criteria. Articles published in languages other than English, French, Spanish, Italian, or German were excluded.

RESULTS

Altogether, 105 articles about SARS-CoV-2-associated neuropathy describing 220 patients with Guillain-Barré syndrome (GBS)44. Finsterer J, Scorza FA. Guillain-Barre syndrome in 220 patients with COVID-19. Egypt J Neurol Psychiatr Neurosurg. 2021;57(1):55. https://doi.org/10.1186/s41983-021-00310-7
https://doi.org/https://doi.org/10.1186/...
and 41 patients with non-GBS neuropathy were retrieved55. Bureau BL, Obeidat A, Dhariwal MS, Jha P. Peripheral Neuropathy as a Complication of SARS-Cov-2. Cureus. 2020 Nov;12(11):e11452. https://doi.org/10.7759/cureus.11452
https://doi.org/https://doi.org/10.7759/...
,66. Cabañes-Martínez L, Villadóniga M, González-Rodríguez L, Araque L, Díaz-Cid A, Ruz-Caracuel I, et al. Neuromuscular involvement in COVID-19 critically ill patients. Clin Neurophysiol. 2020 Dec;131(12):2809-16. https://doi.org/10.1016/j.clinph.2020.09.017
https://doi.org/https://doi.org/10.1016/...
,77. Needham E, Newcombe V, Michell A, Thornton R, Grainger A, Anwar F, et al. Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19. J Neurol. 2020 Nov:1-5. https://doi.org/10.1007/s00415-020-10321-8
https://doi.org/https://doi.org/10.1007/...
,88. Faqihi F, Alharthy A, Memish ZA, Kutsogiannis DJ, Brindley PG, Karakitsos D. Peripheral neuropathy in severe COVID-19 resolved with therapeutic plasma exchange. Clin Case Rep. 2020 Oct;8(12):3234-9. https://doi.org/10.1002/ccr3.3397
https://doi.org/https://doi.org/10.1002/...
,99. Bellinghausen AL, LaBuzetta JN, Chu F, Novelli F, Rodelo AR, Owens RL. Lessons from an ICU recovery clinic: two cases of meralgia paresthetica after prone positioning to treat COVID-19-associated ARDS and modification of unit practices. Crit Care. 2020 Sep;24(1):580. https://doi.org/10.1186/s13054-020-03289-4
https://doi.org/https://doi.org/10.1186/...
,1010. Sánchez-Soblechero A, García CA, Sáez Ansotegui A, Fernández-Lorente J, Catalina-Álvarez I, Grandas F, et al. Upper trunk brachial plexopathy as a consequence of prone positioning due to SARS-CoV-2 acute respiratory distress syndrome. Muscle Nerve. 2020 Nov;62(5):E76-E78. https://doi.org/10.1002/mus.27055
https://doi.org/https://doi.org/10.1002/...
,1111. Abdelnour L, Eltahir Abdalla M, Babiker S. COVID 19 infection presenting as motor peripheral neuropathy. J Formos Med Assoc. 2020 Jun;119(6):1119-20. https://doi.org/10.1016/j.jfma.2020.04.024
https://doi.org/https://doi.org/10.1016/...
,1212. Odriozola A, Ortega L, Martinez L, Odriozola S, Torrens A, Corroleu D, et al. Widespread sensory neuropathy in diabetic patients hospitalized with severe COVID-19 infection. Diabetes Res Clin Pract. 2020 Dec:108631. https://doi.org/10.1016/j.diabres.2020.108631
https://doi.org/https://doi.org/10.1016/...
,1313. García-Moncó JC, Cabrera-Muras A, Collía-Fernández A, Erburu-Iriarte M, Rodrigo-Armenteros P, Oyarzun-Irazu I, et al. Neurological reasons for consultation and hospitalization during the COVID-19 pandemic. Neurol Sci. 2020 Nov;41(11):3031-8. https://doi.org/10.1007/s10072-020-04714-w.
https://doi.org/https://doi.org/10.1007/...
,1414. Miller C, O'Sullivan J, Jeffrey J, Power D. Brachial plexus neuropathies during the COVID-19 pandemic: a retrospective case series of 15 patients in critical care. Phys Ther. 2021 Jan;101(1):pzaa191. https://doi.org/10.1093/ptj/pzaa191
https://doi.org/https://doi.org/10.1093/...
. The age of these 261 patients, reported in 244 of them, ranged from 8 to 94 years. In total, 253 patients had their gender reported, 179 being males and 74 being females. Latency between the onset of viral infection and onset of neuropathy was reported in 168 patients and ranged from -10 to 90 days. Neuropathy was classified in 257 patients. Two-hundred and twenty patients were diagnosed as GBS, four were diagnosed with critical illness neuropathy66. Cabañes-Martínez L, Villadóniga M, González-Rodríguez L, Araque L, Díaz-Cid A, Ruz-Caracuel I, et al. Neuromuscular involvement in COVID-19 critically ill patients. Clin Neurophysiol. 2020 Dec;131(12):2809-16. https://doi.org/10.1016/j.clinph.2020.09.017
https://doi.org/https://doi.org/10.1016/...
, eleven with mononeuritis multiplex77. Needham E, Newcombe V, Michell A, Thornton R, Grainger A, Anwar F, et al. Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19. J Neurol. 2020 Nov:1-5. https://doi.org/10.1007/s00415-020-10321-8
https://doi.org/https://doi.org/10.1007/...
, sixteen with plexopathy1010. Sánchez-Soblechero A, García CA, Sáez Ansotegui A, Fernández-Lorente J, Catalina-Álvarez I, Grandas F, et al. Upper trunk brachial plexopathy as a consequence of prone positioning due to SARS-CoV-2 acute respiratory distress syndrome. Muscle Nerve. 2020 Nov;62(5):E76-E78. https://doi.org/10.1002/mus.27055
https://doi.org/https://doi.org/10.1002/...
, four with isolated sensory neuropathy1212. Odriozola A, Ortega L, Martinez L, Odriozola S, Torrens A, Corroleu D, et al. Widespread sensory neuropathy in diabetic patients hospitalized with severe COVID-19 infection. Diabetes Res Clin Pract. 2020 Dec:108631. https://doi.org/10.1016/j.diabres.2020.108631
https://doi.org/https://doi.org/10.1016/...
, and two with meralgia paresthetica99. Bellinghausen AL, LaBuzetta JN, Chu F, Novelli F, Rodelo AR, Owens RL. Lessons from an ICU recovery clinic: two cases of meralgia paresthetica after prone positioning to treat COVID-19-associated ARDS and modification of unit practices. Crit Care. 2020 Sep;24(1):580. https://doi.org/10.1186/s13054-020-03289-4
https://doi.org/https://doi.org/10.1186/...
. Risk factors for neuropathy identified were pre-existing diabetes, obesity, drug use, and prolonged stay in the intensive care unit (ICU). Drugs known to cause neuropathy and given to patients included daptomycin1515. Kushlaf HA. Emerging toxic neuropathies and myopathies. Neurol Clin. 2011 Aug;29(3):679-87. https://doi.org/10.1016/j.ncl.2011.05.009
https://doi.org/https://doi.org/10.1016/...
, linezolid1616. Pilania RK, Arora A, Agarwal A, Jindal AK, Aggarwal K, Krishnan G, et al. Linezolid-induced mitochondrial toxicity presenting as retinal nerve fiber layer microcysts and optic and peripheral neuropathy in a patient with chronic granulomatous disease. Retin Cases Brief Rep. 2021 May;15(3):224-9. https://doi.org/10.1097/ICB.0000000000000777
https://doi.org/https://doi.org/10.1097/...
, lopinavir1717. Khanlou H, Valdes-Sueiras M, Farthing C. Peripheral neuropathy induced by lopinavir-saquinavir-ritonavir combination therapy in an HIV-infected patient. J Int Assoc Physicians AIDS Care (Chic). 2007 Sep;6(3):155. https://doi.org/10.1177/1545109707302756.
https://doi.org/https://doi.org/10.1177/...
, ritonavir1818. Lorber M. A case of possible darunavir/ritonavir-induced peripheral neuropathy: case description and review of the literature. J Int Assoc Provid AIDS Care. 2013 May-Jun;12(3):162-5. https://doi.org/10.1177/2325957412471993
https://doi.org/https://doi.org/10.1177/...
, hydro-chloroquine1919. Becerra-Cuñat JL, Coll-Cantí J, Gelpí-Mantius E, Ferrer-Avellí X, Lozano-Sánchez M, Millán-Torné M, et al. Miopatía y neuropatía inducida por cloroquina: tetraparesia progresiva con arreflexia que simula una polirradiculoneuropatía. A propósito de dos casos. Rev Neurol. 2003 Mar;36(6):523-6. https://doi.org/10.33588/rn.3606.2002407
https://doi.org/https://doi.org/10.33588...
, cisatracurium2020. Fodale V, Praticò C, Girlanda P, Baradello A, Lucanto T, Rodolico C, et al. Acute motor axonal polyneuropathy after a cisatracurium infusion and concomitant corticosteroid therapy. Br J Anaesth. 2004 Feb;92(2):289-93. https://doi.org/10.1093/bja/aeh040
https://doi.org/https://doi.org/10.1093/...
, clindamycin2121. Thomas RJ. Neurotoxicity of antibacterial therapy. South Med J. 1994 Sep;87(9):869-74. https://doi.org/10.1097/00007611-199409000-00001
https://doi.org/https://doi.org/10.1097/...
, tocilizumab2222. Sugiura F, Kojima T, Oguchi T, Urata S, Yuzawa Y, Sakakibara A, Hayashi H, Nishimoto N, Ishiguro N. A case of peripheral neuropathy and skin ulcer in a patient with rheumatoid arthritis after a single infusion of tocilizumab. Mod Rheumatol. 2009;19(2):199-203. https://doi.org/10.1007/s10165-008-0132-2
https://doi.org/https://doi.org/10.1007/...
, and glucocorticoids2323. Zorowitz RD. ICU-acquired weakness: a rehabilitation perspective of diagnosis, treatment, and functional management. Brust. 2016 Oct;150(4):966-971. https://doi.org/10.1016/j.chest.2016.06.006
https://doi.org/https://doi.org/10.1016/...
,2424. Ghasemiyeh P, Borhani-Haghighi A, Karimzadeh I, Mohammadi-Samani S, Vazin A, Safari A, Qureshi AI. Major Neurologic Adverse Drug Reactions, Potential Drug-Drug Interactions and Pharmacokinetic Aspects of Drugs Used in COVID-19 Patients with Stroke: A Narrative Review. Ther Clin Risk Manag. 2020 Jun 30;16:595-605. https://doi.org/10.2147/TCRM.S259152
https://doi.org/https://doi.org/10.2147/...
. Compression neuropathy was diagnosed in 18 cases99. Bellinghausen AL, LaBuzetta JN, Chu F, Novelli F, Rodelo AR, Owens RL. Lessons from an ICU recovery clinic: two cases of meralgia paresthetica after prone positioning to treat COVID-19-associated ARDS and modification of unit practices. Crit Care. 2020 Sep;24(1):580. https://doi.org/10.1186/s13054-020-03289-4
https://doi.org/https://doi.org/10.1186/...
,1010. Sánchez-Soblechero A, García CA, Sáez Ansotegui A, Fernández-Lorente J, Catalina-Álvarez I, Grandas F, et al. Upper trunk brachial plexopathy as a consequence of prone positioning due to SARS-CoV-2 acute respiratory distress syndrome. Muscle Nerve. 2020 Nov;62(5):E76-E78. https://doi.org/10.1002/mus.27055
https://doi.org/https://doi.org/10.1002/...
,1414. Miller C, O'Sullivan J, Jeffrey J, Power D. Brachial plexus neuropathies during the COVID-19 pandemic: a retrospective case series of 15 patients in critical care. Phys Ther. 2021 Jan;101(1):pzaa191. https://doi.org/10.1093/ptj/pzaa191
https://doi.org/https://doi.org/10.1093/...
. Nerve conduction studies (NCSs) showed axonal lesion in four patients66. Cabañes-Martínez L, Villadóniga M, González-Rodríguez L, Araque L, Díaz-Cid A, Ruz-Caracuel I, et al. Neuromuscular involvement in COVID-19 critically ill patients. Clin Neurophysiol. 2020 Dec;131(12):2809-16. https://doi.org/10.1016/j.clinph.2020.09.017
https://doi.org/https://doi.org/10.1016/...
and plexopathy in one patient1010. Sánchez-Soblechero A, García CA, Sáez Ansotegui A, Fernández-Lorente J, Catalina-Álvarez I, Grandas F, et al. Upper trunk brachial plexopathy as a consequence of prone positioning due to SARS-CoV-2 acute respiratory distress syndrome. Muscle Nerve. 2020 Nov;62(5):E76-E78. https://doi.org/10.1002/mus.27055
https://doi.org/https://doi.org/10.1002/...
. GBS subtypes identified were acute inflammatory demyelinating neuropathy (AIDP) in 118 patients, acute motor axonal neuropathy (AMAN) in 13 patients, acute motor and sensory axonal neuropathy (AMSAN) in 11 patients, Miller-Fisher syndrome in 7 patients, polyneuritis cranialis (PNC) in 2 patients, and the pharyngeal, cervical, and brachial (PCB) variant in 1 patient. Treatment of non-GBS neuropathy was reported in three cases and included steroids, intravenous immunoglobulins (IVIG), gabapentin (GBT), and capsaicin (Table 1). Therapy of GBS comprised IVIG, plasma exchange, steroids, or artificial ventilation.

Table 1.
List of patients with SARS-CoV-2-associated neuropathy of peripheral nerves published until the end of December 2020.

The four non-GBS neuropathy patients with diabetes but without clinical neuropathy reported by Odriozola et al. did not undergo NCSs, but the sensory testing indicated development of sensory neuropathy during the SARS-CoV-2 infection1212. Odriozola A, Ortega L, Martinez L, Odriozola S, Torrens A, Corroleu D, et al. Widespread sensory neuropathy in diabetic patients hospitalized with severe COVID-19 infection. Diabetes Res Clin Pract. 2020 Dec:108631. https://doi.org/10.1016/j.diabres.2020.108631
https://doi.org/https://doi.org/10.1016/...
. Since all four patients had diabetes and received neurotoxic drugs during hospitalisation, it is conceivable that both the infection and the neurotoxic drugs turned a previously subclinical neuropathy into a symptomatic neuropathy. Whether these patients also had subclinical motor involvement remains speculative. In the study by Garcia-Monco et al. on 35 patients with neurological presentation at onset of the SARS-CoV-2 infection, one presented with peripheral neuropathy1313. García-Moncó JC, Cabrera-Muras A, Collía-Fernández A, Erburu-Iriarte M, Rodrigo-Armenteros P, Oyarzun-Irazu I, et al. Neurological reasons for consultation and hospitalization during the COVID-19 pandemic. Neurol Sci. 2020 Nov;41(11):3031-8. https://doi.org/10.1007/s10072-020-04714-w.
https://doi.org/https://doi.org/10.1007/...
. Unfortunately, no further details about this patient were provided. A disadvantage of the study of 15 patients with brachial plexopathy conducted by Miller et al. is that the latency between onset of COVID-19 and onset of neuropathy, treatment, and outcome were not provided and that no NCSs had been carried out1414. Miller C, O'Sullivan J, Jeffrey J, Power D. Brachial plexus neuropathies during the COVID-19 pandemic: a retrospective case series of 15 patients in critical care. Phys Ther. 2021 Jan;101(1):pzaa191. https://doi.org/10.1093/ptj/pzaa191
https://doi.org/https://doi.org/10.1093/...
. In the case reported by Faquihi et al., weakness of lower limbs had developed already prior to application of lopinavir/ritonavir, ribavirin, interferon beta-1b, broad spectrum antibiotics, vasopressors, and hydrocortisone88. Faqihi F, Alharthy A, Memish ZA, Kutsogiannis DJ, Brindley PG, Karakitsos D. Peripheral neuropathy in severe COVID-19 resolved with therapeutic plasma exchange. Clin Case Rep. 2020 Oct;8(12):3234-9. https://doi.org/10.1002/ccr3.3397
https://doi.org/https://doi.org/10.1002/...
. Though this case is described as peripheral neuropathy, initial NCSs only revealed prolonged distal latencies with normal amplitudes, nerve conduction velocities, and F-wave latencies and follow-up NCSs were described as normal88. Faqihi F, Alharthy A, Memish ZA, Kutsogiannis DJ, Brindley PG, Karakitsos D. Peripheral neuropathy in severe COVID-19 resolved with therapeutic plasma exchange. Clin Case Rep. 2020 Oct;8(12):3234-9. https://doi.org/10.1002/ccr3.3397
https://doi.org/https://doi.org/10.1002/...
. Thus, the diagnosis of “neuropathy” remains questionable.

DISCUSSION

This min-review shows that neuropathy of peripheral nerves, including polyradiculitis, is frequent in COVID-19 patients. The most common causes of SARS-CoV-2-associated peripheral neuropathy include GBS, drugs used to treat symptoms of COVID-19, pre-existing diabetes, and compression neuropathies due to prone bedding in the ICU. Whether diabetes or prolonged ICU stay caused neuropathy in the 13 patients with pre-existing diabetes was not differentiated in the appropriate papers. Few studies have been conducted to assess the prevalence of peripheral neuropathy caused by SARS-CoV-2 infection. In a study carried out in Bergamo on 1,760 COVID-19 patients, 9 patients developed critical illness neuropathy and 3 had peripheral neuropathy2525 Rifino N, Censori B, Agazzi E, Alimonti D, Bonito V, Camera G, et al. Neurologic manifestations in 1760 COVID-19 patients admitted to Papa Giovanni XXIII Hospital, Bergamo, Italy. J Neurol. 2020 Oct:1-8. https://doi.org/10.1007/s00415-020-10251-5
https://doi.org/https://doi.org/10.1007/...
. Unfortunately, no further details about these patients were provided. The estimated incidence of GBS between 3/2020 and 4/2020 was 2.43/100000/y in Northern Italy2626 Filosto M, Cotti Piccinelli S, Gazzina S, Foresti C, Frigeni B, Servalli MC, et al. Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions. J Neurol Neurosurg Psychiatry 2020 Nov:jnnp-2020-324837. https://doi.org/10.1136/jnnp-2020-324837
https://doi.org/https://doi.org/10.1136/...
. Patients requiring prone position for treatment of acute respiratory distress syndrome (ARDS) in the ICU are predisposed to develop compression neuropathy. In a retrospective study of 83 patients with ARDS due to SARS-CoV-2, 12 patients (14.5%) developed peripheral nerve injury2727 Malik GR, Wolfe AR, Soriano R, Rydberg L, Wolfe LF, Deshmukh S, et al. Injury-prone: peripheral nerve injuries associated with prone positioning for COVID-19-related acute respiratory distress syndrome. Br J Anaesth. 2020 Dec;125(6):e478-e80. https://doi.org/10.1016/j.bja.2020.08.045
https://doi.org/https://doi.org/10.1016/...
. One patient in prone position for mechanical ventilation developed unilateral plexopathy. In 15 other patients, brachial plexopathy evolved during ICU stay1414. Miller C, O'Sullivan J, Jeffrey J, Power D. Brachial plexus neuropathies during the COVID-19 pandemic: a retrospective case series of 15 patients in critical care. Phys Ther. 2021 Jan;101(1):pzaa191. https://doi.org/10.1093/ptj/pzaa191
https://doi.org/https://doi.org/10.1093/...
. Among the 11 patients with mononeuritis multiplex reported by Needham et al.77. Needham E, Newcombe V, Michell A, Thornton R, Grainger A, Anwar F, et al. Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19. J Neurol. 2020 Nov:1-5. https://doi.org/10.1007/s00415-020-10321-8
https://doi.org/https://doi.org/10.1007/...
, the etiology of neuropathy remained elusive. Though the authors speculated that distribution of sensory or motor deficits suggested vasculitis, none of the 11 patients had undergone nerve biopsy to confirm or exclude this diagnosis. Concerning GBS, this review shows that SARS-CoV-2-associated GBS is not due to a direct attack of the virus, but rather due to an immunological reaction to the virus.

In none of the patients included in this review were there any indications for viral neuropathy. These findings suggest that SARS-CoV-2 does not damage peripheral nerves by a direct attack but rather by secondary immune mechanisms. Pre-existing damage of peripheral nerves, side effects of drugs used to treat manifestations of COVID-19, and positioning of patients seem to be the most relevant causes of SARS-CoV-2-associated non-GBS related peripheral neuropathy. Accordingly, it is crucial not only to avoid the use of neurotoxic drugs, but also to sufficiently treat pre-existing diabetes, and to avoid bedding of the patients during mechanical ventilation in a position that can favor the development of compression neuropathy. This may help to prevent the development of peripheral neuropathy during SARS-CoV-2 infection.

Peripheral neuropathies in patients with COVID-19 are frequent and mostly result from immune mechanisms and neurotoxic side effects of drugs applied to treat COVID-19 and, to a lesser extent, from the compression of peripheral nerves after prolonged bedding on the ICU. SARS-CoV-2 does not cause viral neuropathy. Neurotoxic drugs such as daptomycin, linezolid, lopinavir, ritonavir, hydro-chloroquine, cisatracurium, clindamycine, and glucocorticoids should be used with caution and patients in the ICU should be appropriately bedded to prevent SARS-CoV-2-associated neuropathy.

References

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Publication Dates

  • Publication in this collection
    19 July 2021
  • Date of issue
    Oct 2021

History

  • Received
    26 Jan 2021
  • Reviewed
    11 Feb 2021
  • Accepted
    21 Mar 2021
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