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Covid-19–Associated Myopathy Caused by Type I Interferonopathy


to the Editor:

Syndrome of Kovid-19 infection includes at least one third of patients with myelagias and elevated creatine kinase levels.1-3 Whether the increase in creatine kinase levels is caused by viral infection of muscles, toxic effects of cytokines, or another mechanism is not clear. There are few reports of muscle-biopsy findings in patients with Kovid-19.4 We describe a patient with Kovid-19 infection and myopathy who had a virus-biopsy specimen showing evidence of virus-induced type I interferonopathy.

A 38-year-old man with no recent history of illness or drug use was presented with weakness, myelgia, and fever. He had normalized muscle weakness, which was more severe than even remotely, and was unable to walk, abduct his shoulders, or flex his hips against gravity. Heliotrope rash, Gottron’s signs or papules, and nail-bed changes were absent. She has severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA for bibacilar infiltration and a positive reverse-transcriptase-polymerase-chain-reaction assay. Serum levels of creatine kinase are 29,800 U per liter (reference range, 39 to 308), high sensitivity troponin T 3157 ng per liter (reference range, 0 to 14), and C-reactive protein 55 per liter (reference value). 10), and myoglobinuria was not present. Findings on electrocardiography, echocardiography and cardiac magnetic resonance imaging were common. A description of the methods used for immunohistochemical analysis of muscles is provided. Supplementary Addendum, With full text of this paper available at NEJM.org.

Immunohistochemical analysis of a biopsy specimen from the left deltoid muscle in a patient with Kovid-19.

Panel A shows the predominance of a major-histocompatibility-complex (MHC) class I antigen on the sarcolemma and sarcoplasm of muscle fibers, with a precursor to perifacicular muscle fibers. The expression of MHC class I antigens on capillaries is normal. Panel B shows abnormal expression of exovirus virus resistance protein A (MXA), with prognosis for sarcoplasm and sarcoplasm of muscle fibers, perifacicular muscle fibers, and capillaries. MxA is not usually expressed on capillaries. Abnormal expression of MXA is seen with type I interferonopathies.

A biopsy specimen of his left deltoid muscle showed mild perivascular inflammation in some vessels but no necrotic or regenerated fibers or perifacicular atrophy. Immunohistochemical analysis revealed abnormal expression of major-histocompatibility-complex class I on sarcolemma and sarcoplasm and abnormal presence of myxovirus resistance protein A on muscle fibers and capillaries.Figure 1A and 1B). There was no membrane attack complex deposition on muscle fibers or capillaries. Immunohistochemical testing did not detect SARS-COV-2 in muscle.

They were treated with intravenous remodivir (single initial dose of 200 mg, followed by 100 mg daily for 4 days) and intravenous methylpredisolone (1 g daily for 3 days), followed by oral prednisone (60 mg daily). ). When discharged 14 days after the onset of the disease, he was able to walk and the creatine kinase level was 5130 U per liter.

Myxovirus resistance protein A is a type I interferon-inducible protein expressed in response to viral infection, including SARS-COV-2.5 Deposition of this protein in muscle fibers and capillaries is an early feature of dermatomyositis, which precedes the characteristic perifacicular trophy. Our patient did not have clinical features of dermatomyositis or a complex depiction of membrane attack on capillaries, another feature of dermatomyositis, making it unlikely that he had dermatitis independently of SARS-CoV-2. Increased expression of type I interferes with tissue that regulates other proteins that are toxic to endothelial cells, muscles, and lungs. Findings in a muscle-biopsy specimen from this patient suggest that his SARS-CoV-2 myopathy may also be due to type I interferonopathy.

Giovanna S. Manzano, MD
Jared. Woods, M.D., Ph.D.
Anthony a. Amato, MD
Brigham and Women’s Hospital, Boston, MA

Disclosure forms The full text of this paper is available at NEJM.org provided by the authors.

The paper was published on NEJM.org on November 20, 2020.

  1. 1. Guidan AC, Dear aa. COVID-19 and neuromuscular disorders. Neuroscience 2020; 94:959969.

  2. 2. Guan W.J., Nor zy, Huh, and others. Clinical features of coronavirus virus 2019 in China. N angle j med 2020; 382:17081720.

  3. 3. That lq, Huang T, Wang YQ, and others. Clinical features, discharge rates, and meta-analysis malignancy rates of COVID-19 patients. J med sparse 2020; 92:577583.

  4. 4. Zhang H, Tan z, Sidman RJ, Anjiska Vai, Velayudhan V, Perk j. COVID-19-associated myositis with severe proximal and bulbar weakness. Nervous nerve 2020; 62:E57E60.

  5. 5. Pulia MS, O’Brien T.P., Love pc, Shuman a, Samburski R. Multi-level screening and diagnosis strategy for COVID-19: a model for sustainable testing capability in epidemic response. En med 2020; 52:207214.



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