{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T12:07:21Z","timestamp":1759147641325,"version":"3.41.2"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, but also many other organs and tissues, leading to different pathological pictures, such as those of the musculoskeletal tissues. The present study should be considered as a speculation on the relationship between COVID-19 infection and some frequent musculoskeletal pathologies, in particular sarcopenia, bone loss\/osteoporosis (OP) and fracture risk and osteoarthritis (OA), to hypothesize how the virus acts on these pathologies and consequently on the tissue regeneration\/healing potential. The study focuses in particular on the modalities of interaction of COVID-19 with Angiotensin-Converting Enzyme 2 (ACE2) and on the \u201ccytokine storm.\u201d Knowing the effects of COVID-19 on musculoskeletal tissues could be important also to understand if tissue regenerative\/reparative capacity is compromised, especially in elderly and frail patients. We speculate that ACE2 and serine proteases together with an intense inflammation, immobilization and malnutrition could be the responsible for muscle weakness, altered bone remodeling, increase in bone fracture risk and inflammatory joint pathologies. Future preclinical and clinical studies may focus on the regenerative\/reparative properties of the musculoskeletal tissues after COVID-19 infection, toward a personalized treatment usually based on scaffolds, cells, and growth factors.<\/jats:p>","DOI":"10.3389\/fmed.2022.930789","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T05:46:07Z","timestamp":1657777567000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Speculation on the pathophysiology of musculoskeletal injury with COVID-19 infection"],"prefix":"10.3389","volume":"9","author":[{"given":"Francesca","family":"Veronesi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deyanira","family":"Contartese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Martini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Visani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Fini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.7423","article-title":"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): an update.","volume":"12","author":"Pal","year":"2020","journal-title":"Cureus."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.20.00686","article-title":"Mortality rates of patients with proximal femoral fracture in a worldwide pandemic preliminary results of the Spanish HIP-COVID observational study.","volume":"102","author":"Mu\u00f1oz Vives","year":"2020","journal-title":"Bone Joint Surg Am."},{"key":"B3","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1097\/BOT.0000000000001845","article-title":"Increased mortality and major complications in hip fracture care during the COVID-19 pandemic: a New York City perspective.","volume":"34","author":"Egol","year":"2020","journal-title":"J Orthop Trauma."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1302\/0301-620X.102B9.BJJ-2020-1127.R1","article-title":"The effects of COVID-19 on perioperative morbidity and mortality in patients with hip fractures.","author":"Kayani","year":"2020","journal-title":"Bone Jt J."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1186\/s10195-021-00577-9","article-title":"Early mortality in hip fracture patients admitted during first wave of the COVID-19 pandemic in Northern Italy: a multicentre study.","volume":"22","author":"Dallari","year":"2021","journal-title":"J Orthop Traumatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1302\/2633-1462.25.BJO-2020-0183.R1","article-title":"Early mortality outcomes of patients with fragility hip fracture and concurrent SARS-CoV-2 infection: a systematic review and meta-analysis.","volume":"2","author":"Alcock","year":"2021","journal-title":"Bone Jt Open."},{"key":"B7","doi-asserted-by":"publisher","first-page":"89","DOI":"10.23750\/abm.v91i2.9636","article-title":"Proximal femur fractures in COVID-19 emergency: the experience of two orthopedics and traumatology departments in the first eight weeks of the Italian epidemic.","volume":"91","author":"Maniscalco","year":"2020","journal-title":"Acta Biomed."},{"key":"B8","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s00590-020-02778-0","article-title":"30-day mortality for fractured neck of femur patients with concurrent COVID-19 infection.","volume":"31","author":"Dupley","year":"2021","journal-title":"Eur J Orthop Surg Traumatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1302\/0301-620X.102B10.BJJ-2020-1774","article-title":"Infographic: the effects of COVID-19 on perioperative morbidity and mortality in patients with hip fractures.","author":"Kayani","year":"2020","journal-title":"Bone Jt J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.7150\/ijbs.56657","article-title":"SARS-CoV-2-induced overexpression of miR-4485 suppresses osteogenic differentiation and impairs fracture healing.","volume":"17","author":"Mi","year":"2021","journal-title":"Int J Biol Sci."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.RVW.22.00013","article-title":"What do we need to know about musculoskeletal manifestations of COVID-19?: A systematic review.","volume":"10","author":"Pires","year":"2022","journal-title":"JBJS Rev."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1177\/23743735221102678","article-title":"Impact of COVID-19 pandemic on patients with rheumatic and musculoskeletal diseases: disruptions in care and self-reported outcomes.","volume":"9","author":"Fouad","year":"2022","journal-title":"J Patient Exp."},{"key":"B13","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1152\/japplphysiol.00321.2020","article-title":"The interaction between SARS-CoV-2 and ACE2 may have consequences for skeletal muscle viral susceptibility and myopathies.","volume":"129","author":"Ferrandi","year":"2020","journal-title":"J Appl Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.3201\/eid2607.200445","article-title":"Rhabdomyolysis as potential late complication associated with COVID-19.","volume":"26","author":"Jin","year":"2020","journal-title":"Emerg Infect Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1007\/s10067-020-05178-1","article-title":"Can COVID-19 cause myalgia with a completely different mechanism? A hypothesis.","volume":"39","author":"Kucuk","year":"2020","journal-title":"Clin Rheumatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"E57","DOI":"10.1002\/mus.27003","article-title":"COVID-19\u2013associated myositis with severe proximal and bulbar weakness.","volume":"62","author":"Zhang","year":"2020","journal-title":"Muscle Nerve."},{"key":"B17","doi-asserted-by":"publisher","first-page":"847","DOI":"10.4269\/ajtmh.20-0583","article-title":"Case report: a COVID-19 patient presenting with mild rhabdomyolysis.","volume":"103","author":"Uysal","year":"2020","journal-title":"Am J Trop Med Hyg."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.4269\/ajtmh.20-0692","article-title":"Case report: rhabdomyolysis in a patient with COVID-19: a proposed diagnostic-therapeutic algorithm.","volume":"103","author":"Sol\u0131s","year":"2020","journal-title":"Am J Trop Med Hyg."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1016\/j.cgh.2020.04.042","article-title":"Cardiac and muscle injury might partially contribute to elevated aminotransferases in COVID-19 patients.","volume":"18","author":"Xu","year":"2020","journal-title":"Clin Gastroenterol Hepatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China.","volume":"382","author":"Guan","year":"2020","journal-title":"N Engl J Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.2106\/jbjs.20.00847","article-title":"Musculoskeletal consequences of COVID-19.","volume":"102","author":"Disser","year":"2020","journal-title":"J Bone Joint Surg Am."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s15010-022-01858-z","article-title":"Reactive. arthritis occurring after COVID-19 infection: a narrative review.","author":"Slouma","year":"2022","journal-title":"Infection."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1161\/CIRCRESAHA.120.317015","article-title":"Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2.","volume":"126","author":"Gheblawi","year":"2020","journal-title":"Circ Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1002\/path.5471","article-title":"Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19).","volume":"251","author":"Bourgonje","year":"2020","journal-title":"J Pathol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"271.e","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor.","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.594495","article-title":"Body localization of ACE-2: on the trail of the keyhole of SARS-CoV-2.","volume":"7","author":"Salamanna","year":"2020","journal-title":"Front Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"325","DOI":"10.2174\/1568010054022015","article-title":"Osteoblasts and osteoclasts in bone remodeling and inflammation.","volume":"4","author":"Tanaka","year":"2005","journal-title":"Curr Drug Targets Inflamm Allergy."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.115041","article-title":"The angiotensin converting enzyme 2\/angiotensin-(1-7)\/Mas Receptor axis as a key player in alveolar bone remodeling.","volume":"128","author":"Queiroz-Junior","year":"2019","journal-title":"Bone."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1007\/s00705-009-0472-z","article-title":"Potential enhancement of osteoclastogenesis by severe acute respiratory syndrome coronavirus 3a\/X1 protein.","volume":"154","author":"Obitsu","year":"2009","journal-title":"Arch Virol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.canlet.2018.08.027","article-title":"TMPRSS2:ERG gene fusion expression regulates bone markers and enhances the osteoblastic phenotype of prostate cancer bone metastases.","volume":"438","author":"Delliaux","year":"2018","journal-title":"Cancer Lett."},{"key":"B31","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1590\/s0100-879x2010007500088","article-title":"Characterization of angiotensin-converting enzymes 1 and 2 in the soleus and plantaris muscles of rats.","volume":"43","author":"Fernandes","year":"2010","journal-title":"Braz J Med Biol Res."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093449","article-title":"ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis.","volume":"9","author":"Riquelme","year":"2014","journal-title":"PLoS One."},{"key":"B33","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.bbrc.2003.12.143","article-title":"Expression of trypsin-like proteases and proteasenexin-1 in mdx mouse muscles.","volume":"314","author":"Sawada","year":"2004","journal-title":"Biochem Biophys Res Commun."},{"key":"B34","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jamda.2013.11.025","article-title":"Sarcopenia in Asia: consensus report of the Asian working group for sarcopenia.","volume":"15","author":"Chen","year":"2014","journal-title":"J Am Med Dir Assoc."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1002\/art.27476","article-title":"Matriptase is a novel initiator of cartilage matrix degradation in osteoarthritis.","volume":"62","author":"Milner","year":"2010","journal-title":"Arthritis Rheum."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1002\/art.40133","article-title":"Matriptase induction of metalloproteinase-dependent aggrecanolysis in vitro and in vivo promotion of osteoarthritic cartilage damage by multiple mechanisms.","volume":"69","author":"Wilkinson","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2020.104673","article-title":"The interplay between inflammatory pathways and COVID-19: a critical review on pathogenesis and therapeutic options.","volume":"150","author":"Choudhary","year":"2021","journal-title":"Microb Pathog."},{"key":"B38","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.jinf.2020.03.037","article-title":"Cytokine storm in COVID-19 and treatment.","volume":"80","author":"Ye","year":"2020","journal-title":"J Infect."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.666693","article-title":"Interplay of opposing effects of the WNT\/b-catenin pathway and pparg and implications for SARS-CoV2 treatment.","volume":"12","author":"Valle","year":"2021","journal-title":"Front Immunol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"141","DOI":"10.2147\/ORR.S321884","article-title":"Effects of COVID-19 on the musculoskeletal system: clinician\u2019s guide.","volume":"13","author":"Hasan","year":"2021","journal-title":"Orthop Res Rev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/cdd.2016.16554","article-title":"Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis.","volume":"24","author":"Liu","year":"2017","journal-title":"Cell Death Dif."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2013.00106","article-title":"Bone vascularization in normal and disease conditions.","volume":"4","author":"Carulli","year":"2013","journal-title":"Front Endocrinol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1007\/s10072-021-05110-8","article-title":"Clinical and neurophysiological characterization of muscular weakness in severe COVID-19.","volume":"42","author":"Bax","year":"2021","journal-title":"Neurol Sci."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00165","article-title":"WNT signaling and bone: lessons from skeletal dysplasias and disorders.","volume":"11","author":"Huybrechts","year":"2020","journal-title":"Front Endocrinol (Lausanne)."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1016\/j.csbj.2020.08.024","article-title":"The SARS-CoV-2 host cell receptor ACE2 correlates positively with immunotherapy response and is a potential protective factor for cancer progression.","volume":"18","author":"Zhang","year":"2020","journal-title":"Comput Struct Biotechnol J."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00378","article-title":"Crosstalk between Wnt\/b-Catenin and NF-kB Signaling Pathway during inflammation.","volume":"7","author":"Ma","year":"2016","journal-title":"Front Immunol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1056\/nejmra1209390","article-title":"ICU-Acquired weakness and recovery from critical illness.","volume":"370","author":"Kress","year":"2014","journal-title":"N Engl J Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s00223-021-00858-9","article-title":"Diagnosis and management of osteoporosis during COVID-19: systematic review and practical guidance.","volume":"109","author":"Hampson","year":"2021","journal-title":"Calcif Tissue Int."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105591","article-title":"Osteosarcopenia: a narrative review on clinical studies.","volume":"23","author":"Polito","year":"2022","journal-title":"Int J Mol Sci."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.2174\/2772270816666220318103929","article-title":"Increased ACE2, sRAGE, and immune activation, but lowered calcium and magnesium in COVID-19.","author":"Al-Hakeim","year":"2022","journal-title":"Recent Adv Inflamm Allergy Drug Discov."},{"key":"B51","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.jad.2021.10.039","article-title":"Intersections between pneumonia, lowered oxygen saturation percentage and immune activation mediate depression, anxiety, and chronic fatigue syndrome-like symptoms due to COVID-19: a nomothetic network approach.","volume":"297","author":"Al-Jassas","year":"2022","journal-title":"J Affect Disord."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.930789\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T05:46:10Z","timestamp":1657777570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.930789\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":51,"alternative-id":["10.3389\/fmed.2022.930789"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.930789","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2022,7,14]]},"article-number":"930789"}}