{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:51:51Z","timestamp":1777510311382,"version":"3.51.4"},"posted":{"date-parts":[[2026,1,2]]},"group-title":"Immunology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Infection rates involving bacterial and viral pathogens have increased precipitously after the COVID-19 pandemic. While it has been speculated that higher infection rates resulted from increased hospitalizations throughout the pandemic or greater use of antibiotics, precisely why rates remain high today has remained unexplained. Mitochondrial dysfunction is known to occur post-COVID and may disrupt immune responses. Within T cells, SARS-CoV-2 infection is linked to low mitochondrial membrane potential, increased mitochondrial apoptosis, and decreased mitochondrial respiration, which together impact cellular activation and function beyond the acute phase of illness. Here, we demonstrate that decreased mitochondrial function in antigen-specific T cells post-COVID may contribute to higher infection susceptibility by metabolically immobilizing T cell memory responses. Using donor-matched peripheral blood samples from 31 COVID-na\u00efve individuals who subsequently contracted COVID-19, we tracked how influenza A (IAV),\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  (SA), and Varicella-zoster virus (VZV) T cell responses were impacted by COVID-19 infection. We found that gene expression linked to T cell activation decreased but mitochondrial redox pathways increased in CD4 memory T cells post-COVID. However, mitochondrial flux and reactive oxygen species production were limited in a plurality of post-COVID memory T cells after stimulation with IAV, SA, and VZV. Furthermore, we found a disordered relationship between memory T cell mobilization of glycolysis, fatty acid metabolism, and oxidative phosphorylation pathways post-COVID which resulted in diminished use of catabolic pathways including glycolysis and fatty acid oxidation in antigen-specific T cells. Modulation of mitochondrial function with metformin and ubiquinol partially rescued the post-COVID decline in T cell catabolism. Collectively, these findings indicate that COVID-19 infection may have lasting effects on inhibiting T cell memory responses to commonly encountered community-acquired pathogens which can be corrected with commonly available medications. This has significant implications for the clinical care of immunologically vulnerable populations in the post-pandemic era.\n                <\/jats:p>","DOI":"10.64898\/2025.12.31.697156","type":"posted-content","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T06:20:16Z","timestamp":1767421216000},"source":"Crossref","is-referenced-by-count":2,"title":["Post-COVID impairment of memory T cell responses to community-acquired pathogens can be rectified by activating cellular metabolism"],"prefix":"10.64898","author":[{"given":"Daniel D.","family":"Carroll","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamacay","family":"Cira","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago, Chicago IL, 60637 USA"},{"name":"Department of Surgery, TUM University Hospital, Rechts der Isar, TUM School of Medicine and Health, Technical University of Munich, Munich, Bavaria, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Center for Research Informatics, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ue-Yu","family":"Pen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Tieri","sequence":"additional","affiliation":[{"name":"Center for Research Informatics, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Leonor","sequence":"additional","affiliation":[{"name":"Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago IL, 60611 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neda D.","family":"Roofchayee","sequence":"additional","affiliation":[{"name":"Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago IL, 60611 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha S.","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Wahab","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor J.","family":"Koralnik","sequence":"additional","affiliation":[{"name":"Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago IL, 60611 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Alverdy","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjun S.","family":"Raman","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8157-4385","authenticated-orcid":false,"given":"Lavanya","family":"Visvabharathy","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago, Chicago IL, 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026010507200857000_2025.12.31.697156v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28429"},{"key":"2026010507200857000_2025.12.31.697156v1.2","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-023-17406-9"},{"key":"2026010507200857000_2025.12.31.697156v1.3","doi-asserted-by":"crossref","first-page":"796","DOI":"10.7326\/ANNALS-24-03078","article-title":"Impact of the COVID-19 Pandemic on Antibiotic Resistant Infection Burden in U.S. Hospitals: Retrospective Cohort Study of Trends and Risk Factors","volume":"178","year":"2025","journal-title":". 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