Convalescent-anti-SARS-CoV-2-plasma

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 71-year-old man developed necrotising myopathy and concurrent thyroiditis following administration of off-label convalescent-anti-SARS-CoV-2-plasma for COVID-19 pneumonia [route, dosage and duration of treatment to reaction onset not stated].

The man, who had a medical history of hyperlipidemia, hypogonadism (had been receiving testosterone replacement), bronchiolitis associated with hypogammaglobulinaemia (had been receiving treatment with immune globulin), presented to hospital due to shortness of breath, cough, fatigue and myalgias from the previous 1 week. He was a former athlete and had been working out regularly for 45 minutes. Subsequent investigation led to the diagnosis of sever COVID-19 pneumonia. Other laboratory work up revealed elevated levels of CRP, ferritin and D-dimer. He received empirical treatment with ceftriaxone and doxycycline, it was discontinued after normal procalcitonin and negative blood cultures. He also received remdesivir, off-label IV dexamethasone for first 5 days, in addition to his home medication including atorvastatin; however, testosterone replacement was not continued. On day 5 of hospitalisation, hypoxia and oxygen requirement worsened acutely and he was transferred to the intensive care unit. Eventually, he received off label convalescent-anti-SARS-CoV-2-plasma [convalescent plasma] and methylprednisolone 60 mg every 6 hours, in addition to high-flow oxygen. On day 14, he was discharged to medical ward. Further laboratory investigations revealed slightly elevated creatine kinase which was lowered in the following week. On day 16, he demonstrated new onset of muscle weakness amid an attempt to taper his steroid treatment. Physical examination showed symmetrical 4/5 proximal upper extremity strength and 3/5 proximal lower extremity strength. Upper and lower distal extremity strengths were 5/5 bilaterally. Laboratory testing revealed elevated levels of CK, AST and ALT.

The mans treatment with atorvastatin and fenofibrate were discontinued. On day 18, he received immune globulin. In spite of discontinuing hypolipidemic drugs and tapering of the steroids, his serum CK were elevated. Further testing showed lowered thyroid stimulating hormone and elevated free thyroxine, in addition to normal free triiodothyronine levels. Thyroid examination revealed symmetrical, normal-sized and non-tender thyroid without nodules. nodules. A thyroid uptake and scan following capsule of I-123 revealed diffusely decreased thyroid uptake consistent with thyroiditis. Two week later, thyroid panel normalised. A broad differential diagnosis was considered for his myopathy including hyperthyroidism, corticosteroids, dermatomyositis and polymyositis, statin-induced and critical illness myopathy. His hyperthyroidism resolved without medication. He was receiving steroidal therapy. His extensive myositis panel including Jo-1 antibody and Mi-2 antibody were negative. Finally, an immune-mediated myopathy was considered, especially since myopathy occurred 10 days after administration of convalescent-anti-SARS-CoV-2-plasma and he was found to have a concurrent autoimmune thyroiditis. His CK levels rose significantly. His off-label prednisone 30mg twice daily was switched to off- label methylprednisolone 40mg every 8 hours. His CK started lowering. Subsequent, thigh MRI showed mild oedema of the musculature, most prominently involving the vastus lateralis. On day 21, muscle biopsy showed necrotising myopathy with focal perivascular amyloid. Serum light chains showed elevated kappa quantitative-free light chains; however, kappa-lambda- free light chain ratio and lambda quantitative-free light chains were normal. Electromyography revealed diffuse small polyphasic units with early recruitment but also evidence of small fibrillation potentials that persisted proximally and distally compatible with residual abnormalities from the acute myopathic process. Nerve conduction investigation showed lowered amplitudes in the lower extremities greater than upper extremities. Further investigations were compatible with inflammatory/immune myositis potentially associated with COVID-19 infection.