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Respiratory failure due to neuro-COVID

      Highlights

      • The spectrum of SARS-CoV-2 associated neuromuscular disorders causing respiratory not only includes Guillain-Barre syndrome, myasthenia, and inflammatory myopathy.

      Keywords

      Abbreviations:

      CIDP (chronic inflammatory demyelinating poyneuropathy), GBS (Guillain Barre syndrome), ICU (intensive care unit), MMN (multifocal motor neuropathy), NMD (neuromuscular disorder), PTS (Parsonage Turner syndrome), SFN (small fiber neuropathy)

      1. Letter to the editor

      We read with interest the review article by Galassi et al. about the pathophysiology, presentation, and management of SARS-CoV-2 associated acute neuromuscular disorders (NMDs) resulting in respiratory failure [
      • Galassi G.
      • Marchioni A.
      Acute neuromuscular syndromes with respiratory failure during COVID-19 pandemic: where we stand and challenges ahead.
      ]. It was found that the most common acute NMDs due to a SARS-CoV-2 infection and complicated by respiratory failure include myasthenia, Guillain-Barre syndrome (GBS), and inflammatory myopathy (myositis, idiopathic inflammatory myopathy) [
      • Galassi G.
      • Marchioni A.
      Acute neuromuscular syndromes with respiratory failure during COVID-19 pandemic: where we stand and challenges ahead.
      ]. It was concluded that non-invasive monitoring of respiratory muscles could be essential to recognise the onset of respiratory dysfunction in patients with newly evolving or pre-existing NMD during a SARS-COV-2 infection [
      • Galassi G.
      • Marchioni A.
      Acute neuromuscular syndromes with respiratory failure during COVID-19 pandemic: where we stand and challenges ahead.
      ]. The study is appealing but raises concerns that require discussion.
      Respiratory failure in the context of COVID-19 may not only be due to SARS-CoV-2 pneumonia or affection of the respiratory muscles as mentioned in the introduction, but also due to affection of the brainstem, due to pulmonary embolism, or due to cardiac involvement in the SARS-CoV-2 infection. Affection of the brainstem occurs in the context of autoimmune encephalitis, brainstem stroke, or of GBS, subtype brainstem Bickerstaff encephalitis [

      Samal P, Praharaj HN, Mishra B, Sarangi S. Acute Necrotizing Rhombencephalitis and Disemminated Thrombosis After SARS-CoV-2 Infection. Infect Dis Clin Pract (Baltim Md). 2021 Jul;29(4):e260-e261. doi: 10.1097/IPC.0000000000001029.

      ,
      • Warraich M.
      • Bolaji P.
      • Das S.
      Posterior circulation stroke presenting as a new continuous cough: not always COVID-19.
      ,
      • Llorente Ayuso L.
      • Torres Rubio P.
      • Beijinho do Rosário R.F.
      • Giganto Arroyo M.L.
      • Sierra-Hidalgo F.
      Bickerstaff encephalitis after COVID-19.
      ]. Pulmonary embolism as the cause of respiratory failure can occur in the context of immune thrombocytopenia [
      • Elkoumy M.
      • Schoen J.
      • Loew A.
      Management of a severe bilateral pulmonary embolism as a complication of VITT following vaccination with AstraZeneca COVID-19 vaccine.
      ] or aromatase inhibitor therapy [

      Ioannidou L, Dettoraki A, Noni M, Koukou DM, Michalopoulou A, Botsa E, Kapsimali Z, Michos A, Spoulou V, Pergantou H, Kanaka-Gantenbein C. Pulmonary embolism in adolescent with COVID-19 during aromatase inhibitor therapy. Pediatr Pulmonol. 2022 Apr 26:10.1002/ppul.25944. doi: 10.1002/ppul.25944.

      ]. Respiratory insufficiency due to cardiac compromise may occur in the context of heart failure due to SARS-CoV-2 associated myocarditis, pericarditis, or Takotsubo syndrome (TTS) [
      • Frynas-Jończyk K.
      • Ćwiek-Rębowska E.
      • Filipiak-Strzecka D.
      • Szymczyk E.
      • Kasprzak J.D.
      COVID-tsubo: takotsubo syndrome in patient hospitalized due to the SARS-CoV-2 infection.
      ].
      Regarding the neuromuscular causes of respiratory failure in COVID-19 patients, affection of the nerves innervating respiratory muscles or affection of respiratory muscles by critically ill neuropathy or myopathy should be considered. Muscular respiratory failure in COVID-19 patients develops particularly among those who are severely ill and require intensive unit (ICU) management. Particularly, patients on the ICU are at risk of developing toxic neuropathy or myopathy. In addition to critically ill neuropathy / myopathy these patients may develop chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), Parsonage-Turner syndrome (PTS), vasculitic neuropathy, or small fiber neuropathy (SFN) [
      • Oaklander A.L.
      • Mills A.J.
      • Kelley M.
      • Toran L.S.
      • Smith B.
      • Dalakas M.C.
      • et al.
      Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID.
      ,
      • Taga A.
      • Lauria G.
      COVID-19 and the peripheral nervous system. A 2-year review from the pandemic to the vaccine era.
      ]. At least some of these conditions can be complicated by respiratory insufficiency.
      There are also a number of drugs given to patients with severe COVID-19 that damage muscle or nerves. Among these are chloroquine, corticosteroids, remdesivir, or tocilizumab [
      • Sabljić Z.
      • Bašić-Jukić N.
      Toxic myopathy and liver damage caused by concomitant therapy with remdesivir, atorvastatin, ezetimibe, and tacrolimus in a renal transplant patient with recently treated SARS-CoV-2 induced pneumonia: A case report.
      ]. Toxic drug-induced neuropathy / myopathy can affect the respiratory muscles or nerves innervating respiratory muscles and is usually reversible if the toxic compounds are discontinued.
      Overall, the interesting review has some limitations and inconsistencies which challenge the results and their interpretation. Addressing these limitations may upvalue the conclusions. Neuro-COVID of the central or peripheral nervous system can be complicated by respiratory failure. The spectrum of SARS-CoV-2 associated NMDs causing respiratory failure is broader than anticipated and various differentials need to be ruled out before attributing muscular respiratory failure to a NMD.

      Author contribution

      JF: design, literature search, discussion, first draft, critical comments, DM: literature search, discussion, critical comments, final approval.

      Informed consent

      Not applicable.
      The study was approved by the institutional review board.

      Funding

      No funding was received.

      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.

      References

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        • Marchioni A.
        Acute neuromuscular syndromes with respiratory failure during COVID-19 pandemic: where we stand and challenges ahead.
        J Clin Neurosci. 2022 Apr; 29: 264-275https://doi.org/10.1016/j.jocn.2022.03.048
      1. Samal P, Praharaj HN, Mishra B, Sarangi S. Acute Necrotizing Rhombencephalitis and Disemminated Thrombosis After SARS-CoV-2 Infection. Infect Dis Clin Pract (Baltim Md). 2021 Jul;29(4):e260-e261. doi: 10.1097/IPC.0000000000001029.

        • Warraich M.
        • Bolaji P.
        • Das S.
        Posterior circulation stroke presenting as a new continuous cough: not always COVID-19.
        BMJ Case Rep. 2021 Jan 11; 14: e240270
        • Llorente Ayuso L.
        • Torres Rubio P.
        • Beijinho do Rosário R.F.
        • Giganto Arroyo M.L.
        • Sierra-Hidalgo F.
        Bickerstaff encephalitis after COVID-19.
        J Neurol. 2021; 268: 2035-2037
        • Elkoumy M.
        • Schoen J.
        • Loew A.
        Management of a severe bilateral pulmonary embolism as a complication of VITT following vaccination with AstraZeneca COVID-19 vaccine.
        BMJ Case Rep. 2022 May 11; 15: e246770
      2. Ioannidou L, Dettoraki A, Noni M, Koukou DM, Michalopoulou A, Botsa E, Kapsimali Z, Michos A, Spoulou V, Pergantou H, Kanaka-Gantenbein C. Pulmonary embolism in adolescent with COVID-19 during aromatase inhibitor therapy. Pediatr Pulmonol. 2022 Apr 26:10.1002/ppul.25944. doi: 10.1002/ppul.25944.

        • Frynas-Jończyk K.
        • Ćwiek-Rębowska E.
        • Filipiak-Strzecka D.
        • Szymczyk E.
        • Kasprzak J.D.
        COVID-tsubo: takotsubo syndrome in patient hospitalized due to the SARS-CoV-2 infection.
        Pol Arch Intern Med. 2022 May; 6: 16255https://doi.org/10.20452/pamw.16255
        • Oaklander A.L.
        • Mills A.J.
        • Kelley M.
        • Toran L.S.
        • Smith B.
        • Dalakas M.C.
        • et al.
        Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID.
        Neurol Neuroimmunol Neuroinflamm. 2022 Mar 1; 9: e1146
        • Taga A.
        • Lauria G.
        COVID-19 and the peripheral nervous system. A 2-year review from the pandemic to the vaccine era.
        J Peripher Nerv Syst. 2022 Mar; 27: 4-30https://doi.org/10.1111/jns.12482
        • Sabljić Z.
        • Bašić-Jukić N.
        Toxic myopathy and liver damage caused by concomitant therapy with remdesivir, atorvastatin, ezetimibe, and tacrolimus in a renal transplant patient with recently treated SARS-CoV-2 induced pneumonia: A case report.
        Ther Apher Dial. 2022 Apr; 26: 478-479https://doi.org/10.1111/1744-9987.13748