{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T16:06:32Z","timestamp":1779033992862,"version":"3.51.4"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,8]]},"abstract":"<jats:p>\n                    MHC class I polypeptide-related sequence B (MICB) is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (\n                    <jats:italic>MICB<\/jats:italic>\n                    <jats:sup>G406A<\/jats:sup>\n                    ) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from IMPACC. Associations between\n                    <jats:italic>MICB<\/jats:italic>\n                    <jats:sup>G406A<\/jats:sup>\n                    and outcomes were determined by linear regression or Cox proportional hazards models. We also measured immune profiles of peripheral blood and the upper and lower airway. We identified 560 major allele homozygous patients, and 426 and 50 with 1 or 2 copies of the variant allele, respectively.\n                    <jats:italic>MICB<\/jats:italic>\n                    <jats:sup>G406A<\/jats:sup>\n                    conferred reduced odds of severe COVID-19. MICB\n                    <jats:sup>G406A<\/jats:sup>\n                    homozygous participants demonstrated 34% reduced cumulative odds for mechanical ventilation or death and 43% reduced risk for mortality. Patients with MICB\n                    <jats:sup>G406A<\/jats:sup>\n                    variant alleles had reduced soluble inflammatory mediators and differential regulation of multiple immune pathways. These findings demonstrate a potentially novel association between increasing\n                    <jats:italic>MICB<\/jats:italic>\n                    <jats:sup>G406A<\/jats:sup>\n                    variant allele copies and reduced COVID-19 severity, independent of SARS-CoV-2 viral burden and humoral immunity, suggesting the NKG2D-ligand pathway as an intervention target.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.191951","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T12:00:13Z","timestamp":1751544013000},"source":"Crossref","is-referenced-by-count":1,"title":["MICBG406A polymorphism reduces risk of mechanical ventilation and death during viral acute lung injury"],"prefix":"10.1172","volume":"10","author":[{"given":"Harry","family":"Pickering","sequence":"first","affiliation":[{"name":"Pathology and Laboratory Medicine, UCLA, Los Angeles, California, 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