{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:09:41Z","timestamp":1786705781728,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Instituto de SaludCarlos III (ISCIII)-European Union Next Generation MRR funds","award":["ISCIII PI-21\/00971"],"award-info":[{"award-number":["ISCIII PI-21\/00971"]}]},{"name":"Spanish Instituto de SaludCarlos III (ISCIII)-European Union Next Generation MRR funds","award":["PI-22\/00705"],"award-info":[{"award-number":["PI-22\/00705"]}]},{"name":"Spanish Instituto de SaludCarlos III (ISCIII)-European Union Next Generation MRR funds","award":["FI-23\/00207"],"award-info":[{"award-number":["FI-23\/00207"]}]},{"name":"Spanish Instituto de SaludCarlos III (ISCIII)-European Union Next Generation MRR funds","award":["RICORS2040-RD21\/005"],"award-info":[{"award-number":["RICORS2040-RD21\/005"]}]},{"name":"Spanish Instituto de SaludCarlos III (ISCIII)-European Union Next Generation MRR funds","award":["FICYT-AYUD\/2021\/520148"],"award-info":[{"award-number":["FICYT-AYUD\/2021\/520148"]}]},{"name":"Gobierno del Principado de Asturias","award":["ISCIII PI-21\/00971"],"award-info":[{"award-number":["ISCIII PI-21\/00971"]}]},{"name":"Gobierno del Principado de Asturias","award":["PI-22\/00705"],"award-info":[{"award-number":["PI-22\/00705"]}]},{"name":"Gobierno del Principado de Asturias","award":["FI-23\/00207"],"award-info":[{"award-number":["FI-23\/00207"]}]},{"name":"Gobierno del Principado de Asturias","award":["RICORS2040-RD21\/005"],"award-info":[{"award-number":["RICORS2040-RD21\/005"]}]},{"name":"Gobierno del Principado de Asturias","award":["FICYT-AYUD\/2021\/520148"],"award-info":[{"award-number":["FICYT-AYUD\/2021\/520148"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background. The STING protein is activated by the second messenger cGAMP to promote the innate immune response against infections. Beyond this role, a chronically overactive STING signaling has been described in several disorders. Patients with severe COVID-19 exhibit a hyper-inflammatory response (the cytokine storm) that is in part mediated by the cGAS-STING pathway. Several STING inhibitors may protect from severe COVID-19 by down-regulating several inflammatory cytokines. This pathway has been implicated in the establishment of an optimal antiviral vaccine response. STING agonists as adjuvants improved the IgG titers against the SARS-CoV-2 Spike protein vaccines. Methods. We investigated the association between two common functional STING1\/TMEM173 polymorphisms (rs78233829 C&gt;G\/p.Gly230Ala and rs1131769C&gt;T\/p.His232Arg) and severe COVID-19 requiring hospitalization. A total of 801 non-vaccinated and 105 fully vaccinated (mRNA vaccine) patients, as well as 300 population controls, were genotyped. Frequencies between the groups were statistically compared. Results. There were no differences for the STING1 variant frequencies between non-vaccinated patients and controls. Vaccinated patients showed a significantly higher frequency of rs78233829 C (230Gly) compared to non-vaccinated patients (CC vs. CG + GG; p = 0.003; OR = 2.13; 1.29\u20133.50). The two STING1 variants were in strong linkage disequilibrium, with the rs78233829 C haplotypes being significantly more common in the vaccinated (p = 0.02; OR = 1.66; 95%CI = 1.01\u20132.55). We also studied the LTZFL1 rs67959919 G\/A polymorphism that was significantly associated with severe COVID-19 (p &lt; 0.001; OR = 1.83; 95%CI = 1.28\u20132.63). However, there were no differences between the non-vaccinated and vaccinated patients for this polymorphism. Conclusions. We report a significant association between common functional STING1 polymorphisms and the risk of developing severe COVID-19 among fully vaccinated patients.<\/jats:p>","DOI":"10.3390\/life15081171","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T16:04:51Z","timestamp":1753286691000},"page":"1171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of TMEM173\/STING1 Gene Variants with Severe COVID-19 Among Fully Vaccinated vs. Non-Vaccinated Individuals"],"prefix":"10.3390","volume":"15","author":[{"given":"Daniel","family":"V\u00e1zquez-Coto","sequence":"first","affiliation":[{"name":"Gen\u00e9tica Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Garc\u00eda-Clemente","sequence":"additional","affiliation":[{"name":"Neumolog\u00eda, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Medicine Department, Universidad de Oviedo, 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo M.","family":"Albaiceta","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain"},{"name":"Functional Biology Department, Universidad de Oviedo, 33011 Oviedo, Spain"},{"name":"Unidad de Cuidados Intensivos Cardiol\u00f3gicos, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"CIBER-Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias (IOUPA), Universidad de Oviedo, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8793-0213","authenticated-orcid":false,"given":"Laura","family":"Amado","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain"},{"name":"Functional Biology Department, Universidad de Oviedo, 33011 Oviedo, Spain"},{"name":"Unidad de Cuidados Intensivos Cardiol\u00f3gicos, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"CIBER-Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias (IOUPA), Universidad de Oviedo, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena M.","family":"Vega-Prado","sequence":"additional","affiliation":[{"name":"Gen\u00e9tica Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Garc\u00eda-Lago","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Lorca","sequence":"additional","affiliation":[{"name":"Medicine Department, Universidad de Oviedo, 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain"},{"name":"Cardiolog\u00eda, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-4649","authenticated-orcid":false,"given":"Juan","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Gen\u00e9tica Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain"},{"name":"CIBER-Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8649-9150","authenticated-orcid":false,"given":"Eliecer","family":"Coto","sequence":"additional","affiliation":[{"name":"Gen\u00e9tica Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Medicine Department, Universidad de Oviedo, 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101206","DOI":"10.1016\/j.coviro.2022.101206","article-title":"RNA viruses and the cGAS-STING pathway: Reframing our understanding of innate immune sensing","volume":"53","author":"Webb","year":"2022","journal-title":"Curr. 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