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Record W4415532920 · doi:10.70962/jhi.20250149

The seven enigmas of SARS-CoV-2: From the past to the future

2025· article· en· W4415532920 on OpenAlexafffund
Evangelos Andreakos, Lisa M. Arkin, Paul Bastard, Alexandre Bolze, A. Borghesi, Petter Brodin, Jean‐Laurent Casanova, Giorgio Casari, Aurélie Cobat, Beth A. Drolet, Jacques Fellay, Elena W.Y. Hsieh, Isabelle Meyts, Trine H. Mogensen, Vanessa Sancho‐Shimizu, András N. Spaan, Helen C. Su, Donald C. Vinh, Ahmad Yatim, Qian Zhang, Shen‐Ying Zhang, Laurent Abel, Alessandro Aiuti, Saleh Al‐Muhsen, Andrés A. Arias, Hagit Baris Feldman, Anastasiia Bondarenko, Ahmed Aziz Bousfiha, John Christodoulou, Roger Colobrán, Antonio Condino-Neto, Stefan N. Constantinescu, Munis Dündar, Sara Elva Espinosa‐Padilla, Carlos Flores, Antoine Froidure, Guy Gorochov, David Hagin, Rabih Halwani, Lennart Hammarström, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Yu-Lung Lau, Davood Mansouri, László Maródi, Lisa F. P. Ng, Antonio Novelli, Giuseppe Novelli, Satoshi Okada, Keisuke Okamoto, Fırat Özçelik, Qiang Pan‐Hammarström, Rebeca Pérez de Diego, David S. Perlin, Anne Puel, Aurora Pujol, Laurent Rénia, Mohammad Shahrooei, Anna Shcherbina, Ondřej Slabý, Pere Soler‐Palacín, Ivan Tancevski, Stuart G. Tangye, Ahmad Abou Tayoun, Christian W. Thorball, Pierre Tiberghien, Stuart E. Turvey

Bibliographic record

VenueJournal of Human Immunity · 2025
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsMcGill University Health CentreInstitute of Infection and ImmunityHospital for Sick ChildrenUniversity Hospital Foundation
FundersNational Center for Advancing Translational SciencesNational Heart, Lung, and Blood InstituteStaatssekretariat für Bildung, Forschung und InnovationTakeda CanadaNational Institutes of HealthCanadian Institutes of Health ResearchEuropean Academy of Dermatology and VenereologyNHLBI Division of Intramural ResearchPublic Health AgencyNovo NordiskNational Center for Research ResourcesNational Institute of Allergy and Infectious DiseasesFisher Center for Alzheimer's Research FoundationAgence Nationale de la RechercheEuropean CommissionMerck CanadaMinistère de l'Enseignement supérieur, de la Recherche et de l'InnovationBoettcher FoundationInstitut National de la Santé et de la Recherche MédicalePfizerModernaFondation du SouffleStavros Niarchos FoundationCSL BehringInstitut des maladies génétiques ImagineAmgenSt. Giles FoundationSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungHoward Hughes Medical InstituteFondation pour la Recherche MédicaleCancer Research InstitutePublic Health Agency of CanadaNational Science Foundation
KeywordsPandemicDiseasePneumoniaImmunityCoronavirus disease 2019 (COVID-19)Human geneticsInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

Five years ago, we launched the COVID Human Genetic Effort. Our goal was to explain the clinical variability among SARS-CoV-2-exposed individuals by searching for monogenic inborn errors of immunity (IEI) and their phenocopies. We deciphered the pathogenesis of critical COVID-19 pneumonia and multisystemic inflammatory syndrome in children (MIS-C) in ~15% and 2% of cases, respectively, thereby revealing general mechanisms of severe disease. We also defined neuro-COVID-19 genetically and immunologically in one child, while we delineated the immunological mechanisms of COVID-toes in healthy children and young adults, paving the way for their genetic study. Understanding the human genetic and immunological basis of resistance to SARS-CoV-2 infection, long COVID, and myocarditis post mRNA vaccination, has been challenging and investigations remain ongoing. This work highlights the power of patient-based basic research and large-scale international collaborative efforts to discover human genetic and immunological drivers of infectious disease phenotypes, with implications for the timely development of new medical strategies before the next pandemic arrives.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.006
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.006
Threshold uncertainty score0.032

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0060.005
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0020.002
Science and technology studies0.0020.009
Scholarly communication0.0050.015
Open science0.0010.003
Research integrity0.0050.011
Insufficient payload (model declined to judge)0.0030.001

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 head0.043
GPT teacher head0.372
Teacher spread0.329 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

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

Citations3
Published2025
Admission routes2
Has abstractyes

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