{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:40:17Z","timestamp":1769064017166,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T00:00:00Z","timestamp":1740873600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Long COVID represents a significant global health challenge with an unclear etiology. Alongside accumulating evidence of mitochondrial dysfunction in patients with acute SARS\u2010CoV\u20102 infection, a symptomatic overlap exists between long COVID and mitochondrial disorders. However, the genetic underpinnings of mitochondrial dysfunction in long COVID have not been previously explored. We employed whole genome sequencing to analyze 13 patients with severe long COVID to identify genetic defects related to mitochondrial function. We performed extracellular bioenergetics flux analysis on peripheral blood mononuclear cells and proteomics to evaluate cellular bioenergetics and compared the results to those of healthy controls. Our investigation identified 10 variants classified as pathogenic or likely pathogenic and 83 variants of unknown significance affecting a wide range of mitochondria\u2010associated biological functions. Bioenergetics flux analysis in peripheral blood mononuclear cells revealed an altered ATP production rate in four long COVID patients compared to healthy controls. This study presents initial evidence of a potential underlying genetic predisposition to mitochondrial dysfunction in long COVID while demonstrating altered cellular energy capacity in a subset of these patients. These findings open avenues for further research into the role of mitochondrial dysfunction and pathology in patients suffering from long COVID and may pave the way for targeted therapeutic strategies aimed at mitigating mitochondrial dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jmv.70275","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T22:03:44Z","timestamp":1741730624000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Landscape and Mitochondrial Metabolic Dysregulation in Patients Suffering From Severe Long COVID"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0902-352X","authenticated-orcid":false,"given":"Kristoffer Skaalum","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofie Eg","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cagla","family":"C\u00f6mert","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University Aarhus Denmark"},{"name":"Department of Clinical Medicine, Research Unit for Molecular Medicine Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berit","family":"Schi\u00f8ttz\u2010Christensen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Regional Health Research University of Southern Denmark Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Bross","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Research Unit for Molecular Medicine Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Agergaard","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Leth","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University Aarhus Denmark"},{"name":"Department of Infectious Diseases &amp; 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