{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:16:45Z","timestamp":1783577805777,"version":"3.55.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bacterial coinfections in COVID-19 patients present significant clinical challenges, particularly in severe cases. Previous studies have highlighted the role of microRNAs (miRNAs) in regulating immune responses, with miR-146a-5p and miR-21-5p implicated in inflammation and immune modulation. This study examines the effect of bacterial coinfections on the expression levels of these miRNAs in patients with severe COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a cohort study involving Mexican mestizo patients \u226518 years hospitalized with severe COVID-19, confirmed via PCR testing. Patients were categorized based on the presence or absence of bacterial coinfection, determined through bronchial aspirate or sputum culture. Blood samples were collected at admission and after 15 days of hospitalization to measure the relative expression levels of miR-146a-5p and miR-21-5p. Additionally, an\n                      <jats:italic>in vitro<\/jats:italic>\n                      assay was performed using peripheral blood mononuclear cells (PBMCs) exposed to stimuli (LPS, SARS-CoV-2 Spike Protein, and a combination of both).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with bacterial coinfection were older (43 vs. 41 years, p = 0.046) and had a higher BMI than those without (29.40 vs. 27.51 kg\/m2, p = 0.006). The PaO\n                      <jats:sub>2<\/jats:sub>\n                      \/FiO\n                      <jats:sub>2<\/jats:sub>\n                      ratio was significantly lower in co-infected patients (127.50 vs. 163.75 mmHg, p=0.002), who also exhibited higher rates of severe hypoxemia (35.2% vs. 8.7%), greater need for invasive mechanical ventilation (IMV, 96.0% vs. 34.7, p&amp;lt; 0.001), and higher mortality (80.3 vs. 13.0, p&amp;lt; 0.001). No significant differences in miRNA levels were noted after 15 days of hospitalization, regardless of bacterial presence. The\n                      <jats:italic>in vitro<\/jats:italic>\n                      assay did not reveal substantial differences in miRNA expression across stimuli. At the same time,\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      spp. was identified as a predominant coinfecting pathogen, with significantly elevated levels of miR-146a-5p observed in these patients (p = 0.017).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Patients with COVID-19 and bacterial coinfection exhibit worse clinical indicators and increased disease severity, demonstrated by older age, higher BMI, severe hypoxemia, greater need for IMV, and increased mortality. Patients with COVID-19 and coinfection with\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      spp. showed elevated levels of miR-146a-5p.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1846431","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:36:00Z","timestamp":1783575360000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["High levels of miR-146a-5p in COVID-19 patients are associated with Klebsiella lung coinfection"],"prefix":"10.3389","volume":"17","author":[{"given":"Gloria","family":"P\u00e9rez-Rubio","sequence":"first","affiliation":[{"name":"Pneumogenomics Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas","place":["Mexico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo A.","family":"Herrera-Sicairos","sequence":"additional","affiliation":[{"name":"Pneumogenomics Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas","place":["Mexico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Chavez-Galan","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas","place":["Mexico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Campista-Le\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Applied Biology, Faculty of Biology, Universidad Aut\u00f3noma de Sinaloa, Culiac\u00e1n Rosales","place":["Sinaloa, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz Isela","family":"Peinado-Guevara","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Applied Biology, Faculty of Biology, Universidad Aut\u00f3noma de Sinaloa, Culiac\u00e1n Rosales","place":["Sinaloa, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivette","family":"Buendia-Roldan","sequence":"additional","affiliation":[{"name":"Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas","place":["Mexico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucero A.","family":"Ramon-Luing","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas","place":["Mexico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Fricke-Galindo","sequence":"additional","affiliation":[{"name":"Pneumogenomics Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas","place":["Mexico, 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