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Record W3165190268 · doi:10.1172/jci.insight.147535

The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2–infected patients by sex and age

2021· article· en· W3165190268 on OpenAlex
Paula Paccielli Freire, Alexandre H. C. Marques, G. Baiocchi, Lena F. Schimke, Dennyson Leandro M. Fonseca, Ranieri Coelho Salgado, Igor Salerno Filgueiras, Sarah Maria da Silva Napoleão, Desirée Rodrigues Plaça, Karen Tiemi Akashi, Thiago Dominguez Crespo Hirata, Nadia El Khawanky, Lasse M. Giil, Gustavo Cabral‐Miranda, Robson Francisco Carvalho, Luís Carlos de Souza Ferreira, Antônio Condino‐Neto, Helder I. Nakaya, Igor Jurišica, Hans D. Ochs, Niels Olsen Saraiva Câmara, Vera Lúcia Garcia Calich, Otávio Cabral-Marques

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueJCI Insight · 2021
Typearticle
Languageen
FieldMedicine
TopicCOVID-19 Clinical Research Studies
Canadian institutionsUniversity Health Network
FundersUniversidade de São PauloCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundação de Amparo à Pesquisa do Estado de São PauloCanada Foundation for InnovationConselho Nacional de Desenvolvimento Científico e TecnológicoBanco Santander
KeywordsChemokineImmunologyImmune systemCytokineChemokine receptorProinflammatory cytokineEotaxinInterleukin 8MedicineBiologyInflammation

Abstract

fetched live from OpenAlex

The fact that the COVID-19 fatality rate varies by sex and age is poorly understood. Notably, the outcome of SARS-CoV-2 infections mostly depends on the control of cytokine storm and the increasingly recognized pathological role of uncontrolled neutrophil activation. Here, we used an integrative approach with publicly available RNA-Seq data sets of nasopharyngeal swabs and peripheral blood leukocytes from patients with SARS-CoV-2, according to sex and age. Female and young patients infected by SARS-CoV-2 exhibited a larger number of differentially expressed genes (DEGs) compared with male and elderly patients, indicating a stronger immune modulation. Among them, we found an association between upregulated cytokine/chemokine- and downregulated neutrophil-related DEGs. This was correlated with a closer relationship between female and young subjects, while the relationship between male and elderly patients was closer still. The association between these cytokine/chemokines and neutrophil DEGs is marked by a strongly correlated interferome network. Here, female patients exhibited reduced transcriptional levels of key proinflammatory/neutrophil-related genes, such as CXCL8 receptors (CXCR1 and CXCR2), IL-1β, S100A9, ITGAM, and DBNL, compared with male patients. These genes are well known to be protective against inflammatory damage. Therefore, our work suggests specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2 and provides a possible association between inverse modulation of cytokine/chemokine and neutrophil transcriptional signatures.

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.

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)0.032
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.093
Threshold uncertainty score0.977

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.032
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 head0.080
GPT teacher head0.379
Teacher spread0.298 · 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