What specific neuromuscular complications can occur in patients who have had COVID-19 (Coronavirus Disease 2019)?

Specific Neuromuscular Complications of COVID-19

COVID-19 causes distinct neuromuscular complications including Guillain-Barré syndrome, critical illness myopathy/polyneuropathy, rhabdomyolysis, myositis, phrenic nerve injury with diaphragm paralysis, and exacerbations of myasthenia gravis. 1, 2

Direct Peripheral Nerve Complications

Guillain-Barré Syndrome (GBS)

• COVID-19-associated GBS presents differently from typical GBS: patients are typically elderly, have concomitant pneumonia or ARDS, show more prevalent demyelinating neuropathy patterns, and have relatively poor outcomes 2
• Multiple case reports document temporal association with COVID-19, though direct causality remains unproven 1, 3
• Both immune-mediated injury and potential direct viral invasion of neurons have been speculated but not consistently demonstrated 1

Cranial Neuropathies

• Olfactory and gustatory dysfunction is now accepted as an early manifestation, with autopsy studies showing inflammation, edema, and axonal damage of the olfactory bulb 2
• The olfactory pathway serves as a suggested portal of entry for SARS-CoV-2 into the brain 2
• Isolated cranial nerve palsies have been documented, including oculomotor, trochlear, and facial nerve involvement 2

Phrenic Nerve Injury

• Unilateral diaphragm paralysis has been reported in case studies following COVID-19 infection, unrelated to mechanical ventilation or iatrogenic neck injury 4
• Patients present with severe dyspnea post-infection despite normal lung parenchyma on CT imaging 4
• A case series of 32 severe COVID-19 survivors identified five patients with unilateral phrenic nerve injury 4
• Many cases likely go undiagnosed since not all centers have access to sonographers experienced in phrenic nerve/diaphragm scanning protocols 4

Muscle-Specific Complications

Myositis and Rhabdomyolysis

• Myalgia ranks among the most common symptoms after fever, cough, and sore throat, with duration correlating to disease severity 2
• Some patients develop muscle weakness with elevated creatine kinase alongside elevated acute-phase reactants 2
• Skeletal muscle injury occurs in 10.7% of COVID-19 cases, presenting with myopathic changes on EMG rather than denervation patterns 5
• All patients with myositis/rhabdomyolysis had severe respiratory complications 2

Viral-Induced Myopathy of Respiratory Muscles

• 76% of COVID-19 patients requiring mechanical ventilation showed at least one sonographic abnormality of diaphragm muscle structure or function, compared to 45% in non-COVID-19 mechanically ventilated patients 4
• Mean diaphragm thickening ratio in COVID-19 patients (1.14±0.19) was significantly lower than non-COVID-19 patients (1.53±0.46, p=0.0278) 4
• Epimysal and perimysal fibrosis develops from direct viral-induced damage 4
• 88% of all COVID-19 patients and 65% of non-hospitalized patients demonstrated respiratory muscle weakness at 5 months post-infection 4

Ventilator-Induced Diaphragm Dysfunction (VIDD)

• Profound atrophy and weakness occur rapidly in patients requiring mechanical ventilation 4
• This represents a compounding factor on top of direct viral damage to respiratory muscles 4

Neuromuscular Junction Disorders

Myasthenia Gravis Exacerbations

• A handful of myasthenia gravis patients experienced disease exacerbation after acquiring COVID-19 2
• Most recovered with either intravenous immunoglobulins or steroids 2
• COVID-19 can trigger exacerbations of preexisting neuromuscular conditions 1

Critical Illness-Associated Complications

Critical Illness Myopathy/Polyneuropathy

• Mixed axonal neuropathy and primary myopathy are the predominant neuromuscular findings in COVID-19 patients, particularly those with severe disease requiring ICU care 5
• Severe infections lead to critical illness myopathy/polyneuropathy as a distinct complication 1
• Evidence suggests direct viral injury of motor units, though these are fundamentally different from motor neuron disease 5

Central Nervous System Effects on Motor Control

Respiratory Control Center Damage

• Post-mortem analysis demonstrated histological evidence of viral infiltration and pathology to the respiratory control center in patients with severe COVID-19 4
• This suggests the neuromuscular effects are not purely peripheral but involve central neural control mechanisms 4

Common Clinical Pitfalls

• Do not assume respiratory symptoms are purely pulmonary: 76% of post-COVID patients with diaphragm abnormalities had no difference in mechanical ventilation duration compared to controls, suggesting direct viral effects 4
• Fasciculations can occur in COVID-19 but differ in distribution and associated findings from motor neuron disease 5
• It is difficult to differentiate primary viral injury from secondary systemic involvement, particularly in ICU settings 5
• Nerve conduction studies are essential: they help identify axonal neuropathy patterns common in COVID-19 versus the patterns seen in other neuromuscular diseases 5
• Monitor for evolving patterns: COVID-19 neurological manifestations should plateau or improve, unlike progressive neurodegenerative conditions 5