{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:58:31Z","timestamp":1785869911203,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>COVID\u201019 has been associated with both respiratory (diaphragm) and non\u2010respiratory (limb) muscle atrophy. It is unclear if SARS\u2010CoV\u20102 infection of skeletal muscle plays a role in these changes. This study sought to: 1) determine if cells comprising skeletal muscle tissue, particularly myofibres, express the molecular components required for SARS\u2010CoV\u20102 infection; 2) assess the capacity for direct SARS\u2010CoV\u20102 infection and its impact on atrophy pathway genes in myogenic cells; and 3) in an animal model of COVID\u201019, examine the relationship between viral infection of skeletal muscle and myofibre atrophy within the diaphragm and limb muscles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used in silico bioinformatics analysis of published human single cell RNA\u2010seq datasets, as well as direct qPCR examination of human myotubes and diaphragm biopsies, to assess expression of key genes involved in SARS\u2010CoV\u20102 cellular entry. In\u00a0Vitro, we determined the ability of SARS\u2010CoV\u20102 to directly infect myogenic cells and employed qPCR to assess the impact on muscle atrophy pathway genes (ubiquitin\u2010proteasome, autophagy). In\u00a0vivo, the diaphragm and quadriceps of Roborovski hamsters with SARS\u2010CoV\u20102 respiratory infection were examined at day 3 post\u2010inoculation to evaluate the relationship between atrophy pathway and SARS\u2010CoV\u20102 transcripts by qPCR, as well as histological measurements of myofibre morphology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Angiotensin converting enzyme 2 (ACE2), the primary receptor for SARS\u2010CoV\u20102, as well as cooperating proteases (furin, cathepsins B and L), are expressed by myofibres. ACE2 expression was increased 5\u2010fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) in the diaphragms of mechanically ventilated human subjects compared to controls. In\u00a0Vitro, a time\u2010dependent increase of SARS\u2010CoV\u20102 transcript levels was observed in myotubes directly exposed to the virus (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). This was associated with downregulation of the ubiquitin ligase MuRF1 (by 64%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002) and the autophagy gene LC3B (by 31%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). In contrast, in\u00a0vivo infection led to upregulation of MuRF1 in quadriceps (23\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0007) and autophagy genes in both quadriceps (5.2\u2010fold for Gabarapl1,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03; 7\u2010fold for p62,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002) and diaphragm (2.2\u2010fold for Gabarapl1,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03; 2.3\u2010fold for p62,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.057). In infected hamsters the diaphragm lacked viral transcripts but exhibited atrophy (48% decrease in myofibre area;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), whereas the quadriceps lacked myofibre atrophy despite elevated viral transcripts in the muscle.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although myogenic cells express the genes required for SARS\u2010CoV\u20102 entry and can be directly infected, there was no evident relationship between viral transcript levels and manifestations of atrophy, either in\u00a0vitro or in\u00a0vivo. Our results do not support direct myofibre infection by SARS\u2010CoV\u20102 as a likely cause of atrophy in COVID\u201019.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13705","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:08:27Z","timestamp":1738022907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of SARS\u2010CoV\u20102 Entry Genes in Skeletal Muscle and Impacts of In\u00a0Vitro Versus In\u00a0Vivo Infection"],"prefix":"10.1002","volume":"16","author":[{"given":"Salyan","family":"Bhattarai","sequence":"first","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Respiratory Division Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Department of Biomedical and Molecular Sciences Queens University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liang","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Respiratory Division Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Gusev","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Respiratory Division Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qutayba","family":"Hamid","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Respiratory Division Department of Medicine McGill University  Montreal Quebec Canada"},{"name":"Sharjah Institute for Medical Research University of Sharjah  UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ding","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Respiratory Division Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maziar","family":"Divangahi","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Respiratory Division Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7952-0222","authenticated-orcid":false,"given":"Basil\u00a0J.","family":"Petrof","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Respiratory Division Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"issue":"8","key":"e_1_2_7_2_1","first-page":"915","article-title":"Characteristics, Outcomes and Global Trends of Respiratory Support in Patients Hospitalized With COVID\u201019 Pneumonia: A Scoping Review","volume":"87","author":"Radovanovic D.","year":"2021","journal-title":"Minerva 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