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Record W4411981916 · doi:10.1172/jci.insight.191951

MICBG406A polymorphism reduces risk of mechanical ventilation and death during viral acute lung injury

2025· article· en· W4411981916 on OpenAlexaff
Harry Pickering, Narges Alipanah, Ernie Chen, Dylan Duchen, Holden T. Maecker, Seunghee Kim‐Schulze, Ruth R. Montgomery, Chris Cotsapas, Hanno Steen, Florian Krammer, Charles Langelier, Ofer Levy, Lindsey R. Baden, Esther Melamed, Lauren I. R. Ehrlich, Grace A. McComsey, Rafick‐Pierre Sékaly, Charles B. Cairns, Elias K. Haddad, Albert C. Shaw, David A. Hafler, David B. Corry, Farrah Kheradmand, Mark A. Atkinson, Scott C. Brakenridge, Nelson Iván Agudelo Higuita, Jordan P. Metcalf, Catherine L. Hough, William B. Messer, Bali Pulendran, Kari C. Nadeau, Mark Davis, Ana Fernández-Sesma, Viviana Simon, Monica Kraft, Christian Bime, David J. Erle, Joanna Schaenman, Al Ozonoff, Bjoern Peters, Steven H. Kleinstein, Alison D. Augustine, Joann Diray‐Arce, Patrice M. Becker, Nadine Rouphael, Matthew C. Altman, Steven E. Bosinger, Walter L. Eckalbar, Carolyn S. Calfee, Oscar A. Aguilar, Elaine F. Reed, John R. Greenland, Daniel R. Calabrese

Bibliographic record

VenueJCI Insight · 2025
Typearticle
Languageen
FieldMedicine
TopicRespiratory Support and Mechanisms
Canadian institutionsInstitute of Infection and Immunity
FundersNational Center for Advancing Translational SciencesNational Institute of Allergy and Infectious DiseasesNational Institute on Drug AbuseNational Institutes of HealthSeqirusBiomedical Advanced Research and Development AuthorityChina Scholarship CouncilNational Institute for Health and Care ResearchModernaParker Institute for Cancer ImmunotherapyBiomedical Laboratory Research and Development, VA Office of Research and DevelopmentGlaxoSmithKlineNational Heart, Lung, and Blood InstitutePfizerBill and Melinda Gates FoundationU.S. Department of Veterans AffairsOffice of Research and DevelopmentSanofiCancer Research InstituteNational Science Foundation
KeywordsMechanical ventilationMedicineLungCoronavirus disease 2019 (COVID-19)Polymorphism (computer science)Internal medicineCardiologyIntensive care medicineBiologyGeneGeneticsGenotypeInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

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 (MICBG406A) 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 MICBG406A 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. MICBG406A conferred reduced odds of severe COVID-19. MICBG406A homozygous participants demonstrated 34% reduced cumulative odds for mechanical ventilation or death and 43% reduced risk for mortality. Patients with MICBG406A variant alleles had reduced soluble inflammatory mediators and differential regulation of multiple immune pathways. These findings demonstrate a potentially novel association between increasing MICBG406A 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.032
Threshold uncertainty score0.446

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.276
Teacher spread0.267 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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