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Is COVID-19-related Guillain-Barré syndrome different?
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We read with interest the report of Guillain-Barré syndrome secondary to SARS-Cov-19 infection (Coen et al. 2020). Recently, there have been multiple reports of Guillain-Barré syndrome (GBS) associated with the COVID-19 infection (Sedaghat and Karimi, 2020, Toscano et al.,, Zhao et al., 2020). Most COVID-19-related GBS presented with acute onset of areflexic quadriparesis. However, there are some important differences to highlight (table 1 ). (Garg et al., 2018). Most patients with COVID-19-related GBS were elderly. Preceding symptoms like ageusia and hyposmia were unique for COVID-19 infection. Patients with COVID-19-related GBS had a severe disease with respiratory failure due to lobar pneumonia and interstitial pneumonitis. They showed ground-glass appearance of lungs on chest computerized tomography. Increased severity of disease is also evident from the electrophysiology study. Where demyelinating neuropathy is more common with typical GBS and GBS related to dengue and Zika virus, majority of COVID-19-related GBS patients had axonal motor (AMAN) and axonal motor-sensory polyneuropathy (AMSAN). A few of these patients showed enhancement of caudal nerve roots on Gadolinium-enhanced MRI of spine. Most COVID-19 patients received hydroxychloroquine, azithromycin, lopinavir and ritonavir in addition to intravenous immunoglobulin (IVIG). However, more than half of patients showed poor outcome in the form of long ICU stay, residual paresis and dysphagia.
Table 1 Differences in the presentation of Typical GBS, Dengue, Zika virus and COVID SARS related GBS.
Feature Typical GBS Dengue-related GBS Zika virus-related GBS COVID SARS related GBS
Geographical distributionAgeSexPreceding illnessMean time to GBSInitial symptomsDysphagiaSignsFacial diplegiaDysautonomiaAtaxiaRespiratory failureOther cranial nerves involvedLeukopeniaThrombocytopeniaNerve conductionCT chestMRI Brain/spineTreatmentOutcome GlobalAll age groupsMales 1.5 times more affectedRespiratory or gastrointestinal< 6 weeksParesthesia, pain followed by weakness of limbsLess commonAreflexic quadreparesisCommonCommonLess common25%Ocular nervesUncommonUncommonAIDP--IVIG, PlasmapherisisGood, persistent disability in 20%-30% Latin America, IndiaAll age groupsMales:Females EqualFever, rash, myalgia, headache1–30 daysAscending weakness, paresthesia, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonLess commonGlossopharyngeal nerveCommonCommonAIDP, AMSAN--IVIG, PlasmapheresisGood Latin America, Europe, East Asia, North AmericalMiddle age to elderlyMore malesFever, headache, rash, arthralgia, diarrhea, conjunctivitis0–10 daysLimb pains, paresthesia, lower limb weakness, facial weaknessMore commonAreflexic quadri/paraparesisCommon (>50%)Common (up to 30%)Common (up to 70%)Less common3rd cranial nerve--AIDP > AMAN, AMSAN--IVIG, PlasmapheresisGood, half may require ICU care China, Iran, Europe, USAUsually elderlyMore malesFever, cough, dyspnea, ageusia, hyposmia5–14 daysParesthesia, lower limb weakness, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonCommon-Common-AMSAN, AMAN, AIDPPneumonia, interstitial pneumonitisEnhancement of caudal nerve rootsIVIG, Lopinavir, ritonavir, HCQ, Azithromycin,Poor, residual weakness, dysphagia, long ICU stay
AIDP – Acute inflammatory demyelinating polyneuropathy, AMAN – Acute motor axonal neuropathy, AMSAN – Acute motor sensory axonal neuropathy.
Is COVID-19-related GBS has a different pathogenesis? The polyneuropathy in GBS is believed to be due to cross-immunity against epitopes of peripheral nerve components that it shares with the epitopes on the cell surface of bacteria that produces an antecedent infection. This mechanism of “molecular mimicry” is best understood with the Campylobacter jejuni -related GBS. C. jejuni expresses various gangliosides antigen on its outer core. Antecedent infection with C. jejuni results in antibody formation against specific gangliosides present on axonal membrane (GM1, GD1a, GalNac-GD1a, GD1b and GQ1b). Presence of these anti-ganglioside antibodies is strongly associated with AMAN, AMSAN and Miller-Fischer variants of GBS (Ogawara et al., 2000).
The cross-immunity between viral antigens and peripheral nerve glycolipids have not been well-documented. Positive GD1a antibody was reported in a few patients with dengue virus-related GBS (Simon et al., 2016). Anti-ganglioside antibody was not found in patients with COVID-19 and Zika virus-related GBS (Cao-Lormeau et al., 2016). This has led to speculation that the neuropathy in viral infections-related GBS could be due to other autoantibodies that are not detected as yet or the viruses produced nerve damage due to other neurotoxic effects. However, there is paucity of evidence of direct infection of peripheral nerves by viruses from the pathological studies. Good response to immunotherapy in viral infection-related GBS is also against the direct neurotoxic effects of viruses. COVID-19 patients with AIDP responded better as compared to those with axonal variants of GBS; a difference also seen in patients with dengue and Zika virus-related GBS. Recently, a good clinical response in pneumonia has been seen in COVID-19 patients with plasma therapy. Does plasma therapy produce good recovery in COVID-19-related GBS is yet to be seen.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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We read with interest the report of Guillain-Barré syndrome secondary to SARS-Cov-19 infection (Coen et al. 2020). Recently, there have been multiple reports of Guillain-Barré syndrome (GBS) associated with the COVID-19 infection (Sedaghat and Karimi, 2020, Toscano et al.,, Zhao et al., 2020). Most COVID-19-related GBS presented with acute onset of areflexic quadriparesis. However, there are some important differences to highlight (table 1 ). (Garg et al., 2018). Most patients with COVID-19-related GBS were elderly. Preceding symptoms like ageusia and hyposmia were unique for COVID-19 infection. Patients with COVID-19-related GBS had a severe disease with respiratory failure due to lobar pneumonia and interstitial pneumonitis. They showed ground-glass appearance of lungs on chest computerized tomography. Increased severity of disease is also evident from the electrophysiology study. Where demyelinating neuropathy is more common with typical GBS and GBS related to dengue and Zika virus, majority of COVID-19-related GBS patients had axonal motor (AMAN) and axonal motor-sensory polyneuropathy (AMSAN). A few of these patients showed enhancement of caudal nerve roots on Gadolinium-enhanced MRI of spine. Most COVID-19 patients received hydroxychloroquine, azithromycin, lopinavir and ritonavir in addition to intravenous immunoglobulin (IVIG). However, more than half of patients showed poor outcome in the form of long ICU stay, residual paresis and dysphagia.
Table 1 Differences in the presentation of Typical GBS, Dengue, Zika virus and COVID SARS related GBS.
Feature Typical GBS Dengue-related GBS Zika virus-related GBS COVID SARS related GBS
Geographical distributionAgeSexPreceding illnessMean time to GBSInitial symptomsDysphagiaSignsFacial diplegiaDysautonomiaAtaxiaRespiratory failureOther cranial nerves involvedLeukopeniaThrombocytopeniaNerve conductionCT chestMRI Brain/spineTreatmentOutcome GlobalAll age groupsMales 1.5 times more affectedRespiratory or gastrointestinal< 6 weeksParesthesia, pain followed by weakness of limbsLess commonAreflexic quadreparesisCommonCommonLess common25%Ocular nervesUncommonUncommonAIDP--IVIG, PlasmapherisisGood, persistent disability in 20%-30% Latin America, IndiaAll age groupsMales:Females EqualFever, rash, myalgia, headache1–30 daysAscending weakness, paresthesia, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonLess commonGlossopharyngeal nerveCommonCommonAIDP, AMSAN--IVIG, PlasmapheresisGood Latin America, Europe, East Asia, North AmericalMiddle age to elderlyMore malesFever, headache, rash, arthralgia, diarrhea, conjunctivitis0–10 daysLimb pains, paresthesia, lower limb weakness, facial weaknessMore commonAreflexic quadri/paraparesisCommon (>50%)Common (up to 30%)Common (up to 70%)Less common3rd cranial nerve--AIDP > AMAN, AMSAN--IVIG, PlasmapheresisGood, half may require ICU care China, Iran, Europe, USAUsually elderlyMore malesFever, cough, dyspnea, ageusia, hyposmia5–14 daysParesthesia, lower limb weakness, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonCommon-Common-AMSAN, AMAN, AIDPPneumonia, interstitial pneumonitisEnhancement of caudal nerve rootsIVIG, Lopinavir, ritonavir, HCQ, Azithromycin,Poor, residual weakness, dysphagia, long ICU stay
AIDP – Acute inflammatory demyelinating polyneuropathy, AMAN – Acute motor axonal neuropathy, AMSAN – Acute motor sensory axonal neuropathy.
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Table 1 Differences in the presentation of Typical GBS, Dengue, Zika virus and COVID SARS related GBS.
Feature Typical GBS Dengue-related GBS Zika virus-related GBS COVID SARS related GBS
Geographical distributionAgeSexPreceding illnessMean time to GBSInitial symptomsDysphagiaSignsFacial diplegiaDysautonomiaAtaxiaRespiratory failureOther cranial nerves involvedLeukopeniaThrombocytopeniaNerve conductionCT chestMRI Brain/spineTreatmentOutcome GlobalAll age groupsMales 1.5 times more affectedRespiratory or gastrointestinal< 6 weeksParesthesia, pain followed by weakness of limbsLess commonAreflexic quadreparesisCommonCommonLess common25%Ocular nervesUncommonUncommonAIDP--IVIG, PlasmapherisisGood, persistent disability in 20%-30% Latin America, IndiaAll age groupsMales:Females EqualFever, rash, myalgia, headache1–30 daysAscending weakness, paresthesia, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonLess commonGlossopharyngeal nerveCommonCommonAIDP, AMSAN--IVIG, PlasmapheresisGood Latin America, Europe, East Asia, North AmericalMiddle age to elderlyMore malesFever, headache, rash, arthralgia, diarrhea, conjunctivitis0–10 daysLimb pains, paresthesia, lower limb weakness, facial weaknessMore commonAreflexic quadri/paraparesisCommon (>50%)Common (up to 30%)Common (up to 70%)Less common3rd cranial nerve--AIDP > AMAN, AMSAN--IVIG, PlasmapheresisGood, half may require ICU care China, Iran, Europe, USAUsually elderlyMore malesFever, cough, dyspnea, ageusia, hyposmia5–14 daysParesthesia, lower limb weakness, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonCommon-Common-AMSAN, AMAN, AIDPPneumonia, interstitial pneumonitisEnhancement of caudal nerve rootsIVIG, Lopinavir, ritonavir, HCQ, Azithromycin,Poor, residual weakness, dysphagia, long ICU stay
AIDP – Acute inflammatory demyelinating polyneuropathy, AMAN – Acute motor axonal neuropathy, AMSAN – Acute motor sensory axonal neuropathy.
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Table 1
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Differences in the presentation of Typical GBS, Dengue, Zika virus and COVID SARS related GBS.
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Differences in the presentation of Typical GBS, Dengue, Zika virus and COVID SARS related GBS.
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Feature Typical GBS Dengue-related GBS Zika virus-related GBS COVID SARS related GBS
Geographical distributionAgeSexPreceding illnessMean time to GBSInitial symptomsDysphagiaSignsFacial diplegiaDysautonomiaAtaxiaRespiratory failureOther cranial nerves involvedLeukopeniaThrombocytopeniaNerve conductionCT chestMRI Brain/spineTreatmentOutcome GlobalAll age groupsMales 1.5 times more affectedRespiratory or gastrointestinal< 6 weeksParesthesia, pain followed by weakness of limbsLess commonAreflexic quadreparesisCommonCommonLess common25%Ocular nervesUncommonUncommonAIDP--IVIG, PlasmapherisisGood, persistent disability in 20%-30% Latin America, IndiaAll age groupsMales:Females EqualFever, rash, myalgia, headache1–30 daysAscending weakness, paresthesia, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonLess commonGlossopharyngeal nerveCommonCommonAIDP, AMSAN--IVIG, PlasmapheresisGood Latin America, Europe, East Asia, North AmericalMiddle age to elderlyMore malesFever, headache, rash, arthralgia, diarrhea, conjunctivitis0–10 daysLimb pains, paresthesia, lower limb weakness, facial weaknessMore commonAreflexic quadri/paraparesisCommon (>50%)Common (up to 30%)Common (up to 70%)Less common3rd cranial nerve--AIDP > AMAN, AMSAN--IVIG, PlasmapheresisGood, half may require ICU care China, Iran, Europe, USAUsually elderlyMore malesFever, cough, dyspnea, ageusia, hyposmia5–14 daysParesthesia, lower limb weakness, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonCommon-Common-AMSAN, AMAN, AIDPPneumonia, interstitial pneumonitisEnhancement of caudal nerve rootsIVIG, Lopinavir, ritonavir, HCQ, Azithromycin,Poor, residual weakness, dysphagia, long ICU stay
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Feature Typical GBS Dengue-related GBS Zika virus-related GBS COVID SARS related GBS
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Feature
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Typical GBS
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Dengue-related GBS
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Zika virus-related GBS
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COVID SARS related GBS
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Geographical distributionAgeSexPreceding illnessMean time to GBSInitial symptomsDysphagiaSignsFacial diplegiaDysautonomiaAtaxiaRespiratory failureOther cranial nerves involvedLeukopeniaThrombocytopeniaNerve conductionCT chestMRI Brain/spineTreatmentOutcome GlobalAll age groupsMales 1.5 times more affectedRespiratory or gastrointestinal< 6 weeksParesthesia, pain followed by weakness of limbsLess commonAreflexic quadreparesisCommonCommonLess common25%Ocular nervesUncommonUncommonAIDP--IVIG, PlasmapherisisGood, persistent disability in 20%-30% Latin America, IndiaAll age groupsMales:Females EqualFever, rash, myalgia, headache1–30 daysAscending weakness, paresthesia, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonLess commonGlossopharyngeal nerveCommonCommonAIDP, AMSAN--IVIG, PlasmapheresisGood Latin America, Europe, East Asia, North AmericalMiddle age to elderlyMore malesFever, headache, rash, arthralgia, diarrhea, conjunctivitis0–10 daysLimb pains, paresthesia, lower limb weakness, facial weaknessMore commonAreflexic quadri/paraparesisCommon (>50%)Common (up to 30%)Common (up to 70%)Less common3rd cranial nerve--AIDP > AMAN, AMSAN--IVIG, PlasmapheresisGood, half may require ICU care China, Iran, Europe, USAUsually elderlyMore malesFever, cough, dyspnea, ageusia, hyposmia5–14 daysParesthesia, lower limb weakness, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonCommon-Common-AMSAN, AMAN, AIDPPneumonia, interstitial pneumonitisEnhancement of caudal nerve rootsIVIG, Lopinavir, ritonavir, HCQ, Azithromycin,Poor, residual weakness, dysphagia, long ICU stay
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Geographical distributionAgeSexPreceding illnessMean time to GBSInitial symptomsDysphagiaSignsFacial diplegiaDysautonomiaAtaxiaRespiratory failureOther cranial nerves involvedLeukopeniaThrombocytopeniaNerve conductionCT chestMRI Brain/spineTreatmentOutcome
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GlobalAll age groupsMales 1.5 times more affectedRespiratory or gastrointestinal< 6 weeksParesthesia, pain followed by weakness of limbsLess commonAreflexic quadreparesisCommonCommonLess common25%Ocular nervesUncommonUncommonAIDP--IVIG, PlasmapherisisGood, persistent disability in 20%-30%
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Latin America, IndiaAll age groupsMales:Females EqualFever, rash, myalgia, headache1–30 daysAscending weakness, paresthesia, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonLess commonGlossopharyngeal nerveCommonCommonAIDP, AMSAN--IVIG, PlasmapheresisGood
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Latin America, Europe, East Asia, North AmericalMiddle age to elderlyMore malesFever, headache, rash, arthralgia, diarrhea, conjunctivitis0–10 daysLimb pains, paresthesia, lower limb weakness, facial weaknessMore commonAreflexic quadri/paraparesisCommon (>50%)Common (up to 30%)Common (up to 70%)Less common3rd cranial nerve--AIDP > AMAN, AMSAN--IVIG, PlasmapheresisGood, half may require ICU care
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China, Iran, Europe, USAUsually elderlyMore malesFever, cough, dyspnea, ageusia, hyposmia5–14 daysParesthesia, lower limb weakness, facial weaknessLess commonAreflexic quadri/paraparesisCommonLess commonLess commonCommon-Common-AMSAN, AMAN, AIDPPneumonia, interstitial pneumonitisEnhancement of caudal nerve rootsIVIG, Lopinavir, ritonavir, HCQ, Azithromycin,Poor, residual weakness, dysphagia, long ICU stay
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AIDP – Acute inflammatory demyelinating polyneuropathy, AMAN – Acute motor axonal neuropathy, AMSAN – Acute motor sensory axonal neuropathy.
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AIDP – Acute inflammatory demyelinating polyneuropathy, AMAN – Acute motor axonal neuropathy, AMSAN – Acute motor sensory axonal neuropathy.
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AIDP – Acute inflammatory demyelinating polyneuropathy, AMAN – Acute motor axonal neuropathy, AMSAN – Acute motor sensory axonal neuropathy.
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Is COVID-19-related GBS has a different pathogenesis? The polyneuropathy in GBS is believed to be due to cross-immunity against epitopes of peripheral nerve components that it shares with the epitopes on the cell surface of bacteria that produces an antecedent infection. This mechanism of “molecular mimicry” is best understood with the Campylobacter jejuni -related GBS. C. jejuni expresses various gangliosides antigen on its outer core. Antecedent infection with C. jejuni results in antibody formation against specific gangliosides present on axonal membrane (GM1, GD1a, GalNac-GD1a, GD1b and GQ1b). Presence of these anti-ganglioside antibodies is strongly associated with AMAN, AMSAN and Miller-Fischer variants of GBS (Ogawara et al., 2000).
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The cross-immunity between viral antigens and peripheral nerve glycolipids have not been well-documented. Positive GD1a antibody was reported in a few patients with dengue virus-related GBS (Simon et al., 2016). Anti-ganglioside antibody was not found in patients with COVID-19 and Zika virus-related GBS (Cao-Lormeau et al., 2016). This has led to speculation that the neuropathy in viral infections-related GBS could be due to other autoantibodies that are not detected as yet or the viruses produced nerve damage due to other neurotoxic effects. However, there is paucity of evidence of direct infection of peripheral nerves by viruses from the pathological studies. Good response to immunotherapy in viral infection-related GBS is also against the direct neurotoxic effects of viruses. COVID-19 patients with AIDP responded better as compared to those with axonal variants of GBS; a difference also seen in patients with dengue and Zika virus-related GBS. Recently, a good clinical response in pneumonia has been seen in COVID-19 patients with plasma therapy. Does plasma therapy produce good recovery in COVID-19-related GBS is yet to be seen.
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Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Declaration of Competing Interest
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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Appendix A Supplementary data
The following are the Supplementary data to this article:Supplementary data 1
Acknowledgement
None.
Funding
The work did not receive any funding. Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.bbi.2020.05.051.
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Appendix A Supplementary data
The following are the Supplementary data to this article:Supplementary data 1
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The following are the Supplementary data to this article:Supplementary data 1
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Supplementary data 1
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Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.bbi.2020.05.051.
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Supplementary data to this article can be found online at https://doi.org/10.1016/j.bbi.2020.05.051.
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