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Record W4396948506 · doi:10.1038/s41467-024-48556-y

Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity

2024· article· en· W4396948506 on OpenAlexafffund
Elsa Brunet‐Ratnasingham, Sacha Morin, Haley E. Randolph, Marjorie Labrecque, Justin Bélair, Raphaël Lima-Barbosa, Amélie Pagliuzza, Lorie Marchitto, Michael Hultström, Julia Niessl, Rose Cloutier, Alina Maria Sreng Flores, Nathalie Brassard, Mehdi Benlarbi, Jérémie Prévost, Shilei Ding, Sai Priya Anand, Gérémy Sannier, Amanda Marks, Dick Wågsäter, Eric Bareke, Hugo Zeberg, Miklós Lipcsey, Robert Frithiof, Anders Larsson, Sirui Zhou, Tomoko Nakanishi, David Morrison, Dani Vézina, Catherine Bourassa, Gabrielle Gendron‐Lepage, Halima Medjahed, Floriane Point, Jonathan Richard, Catherine Larochelle, Alexandre Prat, Janet L. Cunningham, Nathalie Arbour, Madéleine Durand, J. Brent Richards, Kevin R. Moon, Nicolas Chomont, Andrés Finzi, Martine Tétreault, Luis B. Barreiro, Guy Wolf, Daniel E. Kaufmann

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsJewish General HospitalMila - Quebec Artificial Intelligence InstituteMcGill University Health CentreUniversité de MontréalMcGill UniversityCentre Hospitalier de l’Université de Montréal
FundersNational Institute of General Medical SciencesFonds de recherche du Québec – Nature et technologiesFonds de Recherche du Québec - SantéNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchInstitut de Valorisation des DonnéesNational Heart, Lung, and Blood InstituteVetenskapsrådetUniversité de MontréalNational Institutes of HealthSvenska LäkaresällskapetCanada Research ChairsGénome QuébecCanada Foundation for InnovationHjärt-LungfondenCIHR Skin Research Training CentrePublic Health Agency of CanadaGovernment of CanadaPublic Health AgencyCanadian Institute for Advanced ResearchamfAR, The Foundation for AIDS Research
KeywordsAntibodySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)ImmunologyCohortMedicineCluster (spacecraft)ImmunityCase fatality rateImmune systemInflammationVirologyBiologyInternal medicineEpidemiologyDisease

Abstract

fetched live from OpenAlex

Abstract Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4 + T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.

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)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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)0.0020.000

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 head0.069
GPT teacher head0.382
Teacher spread0.313 · 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 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

Citations19
Published2024
Admission routes2
Has abstractyes

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