A temporal association between COVID‐19 vaccination and immune‐mediated necrotizing myopathy

Abstract

Various neuromuscular complications of coronavirus disease 2019 (COVID-19) vaccine have been reported, including Bell′s palsy and Guillain-Barré syndrome.1 However, inflammatory myositis following COVID-19 vaccine has rarely been reported. We report a case of anti-signal recognition particle (SRP) positive immune-mediated necrotizing myopathy (IMNM) after COVID-19 vaccination. A previously healthy 54-y-old man presented with calf muscle tightness 2 wk after the first inoculation of CoronaVac COVID-19 Vaccine (Sinovac Biotech) into his deltoid muscle (Figure 1). He received his second dose of vaccination 3 wk later. A week after the second dose, he developed bilateral proximal upper and lower limb weakness. After 3 wk, he was unable to ambulate and subsequently developed dysarthria and dysphagia. There were no sensory, urinary, or bowel symptoms. On presentation 8 wk after the first vaccination, he had lost 10 kg of weight. On examination, there was atrophy of the quadriceps and supraspinatus muscles. He had dysarthric speech, poor palate elevation, and neck flexion weakness. Limb muscle weakness was predominantly proximal, Medical Research Council (MRC) grade 2/5 in the upper and lower limbs, while distal muscles of the upper and lower limbs were grade 4/5 and 5/5, respectively. Reflexes were reduced in the lower limbs but normal in the upper limbs. Sensory examination was normal. His nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tested with reverse-transcriptase polymerase chain reaction was negative. Serum creatine kinase (CK) was markedly elevated at 27,000 U/L. Nerve conduction studies were normal; needle electromyography (EMG) showed fibrillation potentials and positive sharp waves, and short duration, low amplitude motor unit potentials with early recruitment in the deltoid and iliopsoas muscles. Biopsy of the deltoid muscle showed scattered necrotic and regenerating muscle fibers without marked inflammation (Figure 2). Anti-SRP antibody titers were markedly elevated whereas anti-hydroxyl-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies were negative. A diagnosis of IMNM was made, and he was treated with intravenous immunoglobulin (IVIG) 2 g/kg followed by oral prednisolone 60 mg daily. There was gradual, partial improvement with proximal upper limb power improving to MRC grade 3/5 and resolution of bulbar and neck flexion weakness. Proximal lower limbs remained at 2/5. Whole body computed tomography did not show any malignancy, and the serum CK decreased to 638 U/L 4 weeks after the IVIG. The patient presented with myalgia and proximal muscle weakness after two doses of COVID-19 vaccination. The temporal relationship of the COVID-19 vaccination to the clinical presentation suggests an association between the two. However, the possibility of coincidental occurrence cannot be entirely excluded. COVID-19 infection has been reported to be associated with various skeletal muscle complications, ranging from asymptomatic hyperCKemia, to myalgia, myositis, and rhabdomyolysis.2 Several mechanisms have been hypothesized, which include direct viral invasion of the myocytes or hyperinflammation syndrome. However, evidence favors indirect muscle injury, as an autopsy case–control study showed that most patients who died of COVID-19 had myositis with little evidence of direct muscle infection.3 COVID-19 myositis could, therefore, be due to deposition of virus-antibody complexes on myocytes or expression of muscle antigen on cell membrane induced by the virus and damage by cytokine storm.4 Post-vaccination inflammatory myositis could possibly develop due to the same mechanisms. The vaccine reported here is an inactivated vaccine against COVID-19 that induces the immune system to produce neutralizing antibodies to SARS-CoV-2. Anti-SARS-CoV-2 antibodies may potentially bind to human antigens due to the high antigenic similarity between the spike protein and human proteins. There have been a few cases of inflammatory myositis post COVID-19 vaccination reported to date.5-7 All the myositis profiles were negative, except in two cases where PM/Scl-75 or SAE1 was positive.6 In conclusion, we think that association is not improbable considering the temporal relationship between vaccination and development of myositis. Larger population-based studies would be required to assess any causal-relationship between COVID-19 vaccination and IMNM. Not applicable. None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal′s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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