Acute neuromuscular syndromes with respiratory failure during COVID-19 pandemic: Where we stand and challenges ahead

Abstract

Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus SARS-COV-2, has become a global pandemic threat. SARS- COV-2 is structurally similar to SARS-COV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. While patients typically present with fever, shortness of breath, sore throat, and cough, in some cases neurologic manifestations occur due to both direct and indirect involvement of the nervous system. Case reports include anosmia, ageusia, central respiratory failure, stroke, acute necrotizing hemorrhagic encephalopathy, toxic-metabolic encephalopathy, headache, myalgia, myelitis, ataxia, and various neuropsychiatric manifestations. Some patients with COVID-19 may present with concurrent acute neuromuscular syndromes such as myasthenic crisis (MC), Guillain-Barré syndrome (GBS) and idiopathic inflammatory myopathies (IIM); these conditions coupled with respiratory failure could trigger a life-threatening condition. Here, we review the current state of knowledge on acute neuromuscular syndromes with respiratory failure related to COVID-19 infection in an attempt to clarify and to manage the muscle dysfunction overlapping SARS-COV-2 infection.

Keywords: Acute respiratory distress syndrome; COVID-19; Guillain-Barré syndrome; Idiopathic inflammatory myopathies; Mechanical ventilation; Myasthenic crisis; Non-invasive ventilation.

Fig. 1

Pathophysiology of lung and vascular injury in the course of severe SARS-COV-2. Respiratory failure is the result of the combination of inflammatory alveolar damage and pulmonary perfusion dysfunction. After viral infection, activated neutrophils recruitment and accumulation into the lung induce superoxide radicals and proteolytic enzyme secretion leading to damage in the alveolar-capillary barrier, inflammatory edema formation and activation of coagulation. Endothelial cells infection and endothelitis associated with ACE-2 downregulation cause a dysfunction of pulmonary perfusion regulation, which results in a worsening of the ventilation/perfusion ratio. Endothelial damage and cytokine release in the lung promote pulmonary angiopathy and thrombosis in distal pulmonary branches.

Fig. 2

Pathophysiology of respiratory failure due to acute neuromuscular weakness in the course of SARS-COV-2 infection. During SARS-COV-2 infection, host-virus interaction may trigger an autoimmune process possibly through the mechanism of molecular mimicry, which could promote the onset or worsening of acute neuromuscular diseases. Furthermore, Tregs depletion after viral infection results in a loss of the immune-regulation, leading to development of the cytokine storm and release of autoantibodies. Onset of Guillain-Barré Syndrome or Myasthenia Gravis may precipitate weakness of respiratory muscles. that can ultimately leads to acute hypoventilation and Co2 retention.