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Many individuals who recover from COVID-19 report prolonged dyspnea, sometimes persisting for months. Furthermore, COVID-19 has been linked to systemic and neuronal inflammation which may have downstream impacts on the neural control of breathing. Therefore, we hypothesized that individuals recovered from COVID-19 may exhibit changes in their ventilatory chemosensitivity to carbon dioxide and hypoxia, and that these changes may be linked to systemic inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To test this hypothesis, we measured baseline ventilatory patterns and chemoreflex sensitivity in individuals recovered from COVID-19 (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200977) and individuals with no prior COVID-19 infection (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200941). Peripheral venous blood samples were also collected for inflammatory biomarker expression and profiling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Recovered participants demonstrated a small but progressive decrease in the hypercapnic ventilatory response under a co-stimulus with hypoxia (control vs. 24-month post-recovery;\n                      <jats:italic>p\u2009=<\/jats:italic>\n                      \u20090.023). Additionally, we identified several significant correlations between plasma inflammatory markers and ventilatory chemoreflex characteristics, including a positive correlation between SAA and CRP and the ventilatory response to hypoxia (\n                      <jats:italic>p\u2009&lt;<\/jats:italic>\n                      \u20090.05 within recovered and control cohorts). Finally, expression of six vascular inflammatory markers (Myoglobin, NGAL, MMP-2, OPN, IGFBP-4, and Cystatin C) was unexpectedly decreased in recovered participants compared to the control cohort for up to one-year post recovery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, this data indicates that COVID-19 and other acute viral infections may have a modest impact on the chemoreflex control of breathing as well as systemic inflammatory profiles, and that these changes may be linked to each other. These findings may strengthen our understanding of the pathology of long-COVID symptoms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-025-03473-6","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:05:10Z","timestamp":1768971910000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term impacts of COVID-19 on systemic inflammation and control of breathing reflexes: an observational cohort study"],"prefix":"10.1186","volume":"27","author":[{"given":"Veronica L.","family":"Penuelas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyleen","family":"Frost","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indira S.","family":"Harahap-Carrillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abel","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina V.","family":"Bergersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meera G.","family":"Nair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica C.","family":"Heinrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"3473_CR1","doi-asserted-by":"publisher","unstructured":"van Willigen HDG, Wynberg E, Verveen A, Dijkstra M, Verkaik BJ, Figaroa OJA, de Jong MC, van der Veen ALIP, Makowska A, Koedoot N, Nieuwkerk PT, Boyd A, Prins M, de Jong MD, de Bree GJ, van den Aardweg JG, RECoVERED Study Group. 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