Case Report: Myopathy in Critically Ill COVID-19 Patients: A Consequence of Hyperinflammation?

Abstract

Introduction: COVID-19-associated muscular complications may comprise myalgia, weakness, wasting, and rhabdomyolysis. Skeletal muscle damage in COVID-19 may be due to direct infection by the virus SARS-CoV-2 through interaction with the ACE2 receptor, systemic hyper-inflammatory state with cytokine release and homeostatic perturbation, an autoimmune process, or myotoxic drugs. Disclosing the cause of weakness in an individual patient is therefore difficult. Case Description: We report two patients, who survived typical COVID-19 pneumonia requiring intensive care treatment and who developed early on myalgia and severe proximal weakness in all four limbs. Laboratory exams revealed elevated serum creatine kinase and markedly increased C-reactive protein and interleukin 6, concurring with a systemic inflammatory response. On admission in neurorehabilitation (4 and 7 weeks after COVID-19 onset, respectively), the patients presented with proximal flaccid tetraparesis and limb-girdle muscle atrophy. Motor nerve conduction studies showed decreased amplitude and prolonged duration of compound muscle action potentials (CMAPs) with normal distal motor latencies and normal conduction velocities in median and ulnar nerves. Needle electromyography in proximal muscles revealed spontaneous activity in one and myopathic changes in both patients. Discussion: Clinical, laboratory, and electrodiagnostic findings in these patients were unequivocally consistent with myopathy. Interestingly, increased distal CMAP duration has been described in patients with critical illness myopathy (CIM) and reflects slow muscle fiber conduction velocity due to membrane hypo-excitability, possibly induced by inflammatory cytokines. By analogy with CIM, the pathogenesis of COVID-19-related myopathy might also depend on hyperinflammation and metabolic pathways that may affect muscles in a pathophysiological continuum from hypo-excitability to necrosis.

Keywords: COVID-19; SARS-CoV-2; compound muscle action potential duration; critical illness myopathy; interleukin 6.

Figure 1

Timeline of key events related to COVID-19 and myopathy in patient 1 (green labels) and patient 2 (yellow labels).

Figure 2

Motor nerve conduction studies of patient 1 (A,B) compared to a healthy control subject (C,D). Amplitude and duration of the negative phase of compound muscle action potentials (CMAPs) were measured at a sensitivity of 0.5 mV with a 2 Hz low frequency filter. The cut-off values for distal CMAP duration are according to reported normal values + 2 SD (12). (A) median nerve: distal CMAP amplitude is reduced (4.2 mV), distal motor latency (DML) is normal (3.9 ms), distal CMAP duration is increased (9.3 ms, 127% of upper limit of normal = 7.3 ms), conduction velocity (CV) is 48 m/s. CMAP amplitude and duration did not change between proximal and distal stimulation. Note the broadening and smooth contour of the negative phase of the distal CMAP and the reduction of the ensuing positive phase compared to panel (C) (CMAP duration = 5.7 ms); (B) ulnar nerve: distal CMAP amplitude is slightly reduced (5.7 mV), DML is normal (2.9 ms), distal CMAP duration is increased (13.7 ms, 183% upper limit of normal = 7.5 ms), CV is 55 m/s. CMAP amplitude and duration did not change with proximal stimulation. Note the very prolonged negative phase of the distal CMAP with a long tail and the absence of the ensuing positive phase compared to panel (D) (CMAP duration = 6.3 ms).