{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:24:10Z","timestamp":1792808650957,"version":"4.5.0"},"reference-count":50,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00184"],"award-info":[{"award-number":["PI19\/00184"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/01360"],"award-info":[{"award-number":["PI20\/01360"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de investigaci\u00f3n biom\u00e9dica en red (CIBER)-Enfermedades respiratorias","award":["CB17\/06\/00021"],"award-info":[{"award-number":["CB17\/06\/00021"]}],"id":[{"id":"https:\/\/ror.org\/02g87qh62","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["grant 413\/C\/2021"],"award-info":[{"award-number":["grant 413\/C\/2021"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CM20\/00083"],"award-info":[{"award-number":["CM20\/00083"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,12,6]]},"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Variants in\n                      <jats:italic>IFIH1<\/jats:italic>\n                      , a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that\n                      <jats:italic>IFIH1<\/jats:italic>\n                      rs199076 variants would modulate host response and outcome after severe COVID-19.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      About 227 patients were studied. Patients with the\n                      <jats:italic>IFIH1<\/jats:italic>\n                      rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in\n                      <jats:italic>IL6<\/jats:italic>\n                      expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29\u20134.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01\u20134.87) and serum IL-6. In-silico clinical trials supported these findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      COVID-19 patients with the\n                      <jats:italic>IFIH1<\/jats:italic>\n                      rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CB17\/06\/00021), Instituto de Salud Carlos III (PI19\/00184 and PI20\/01360), and Fundaci\u00f3 La Marat\u00f3 de TV3 (413\/C\/2021).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.73012","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T05:15:20Z","timestamp":1638854120000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.73012","source":"Crossref","is-referenced-by-count":31,"title":["Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8793-0213","authenticated-orcid":true,"given":"Laura","family":"Amado-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Unidad de Cuidados Intensivos Cardiol\u00f3gicos. 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