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Record W3195689953 · doi:10.1038/s41467-021-25040-5

Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS

2021· article· en· W3195689953 on OpenAlexaff
Aartik Sarma, Stephanie A. Christenson, Ashley Byrne, Eran Mick, Angela Oliveira Pisco, Catherine DeVoe, Thomas Deiss, Rajani Ghale, Beth Shoshana Zha, Alexandra Tsitsiklis, Alejandra Jáuregui, Farzad Moazed, Angela M. Detweiler, Natasha Spottiswoode, Pratik Sinha, Norma Neff, Michelle Tan, Paula Hayakawa Serpa, Andrew Willmore, K. Mark Ansel, Jennifer G. Wilson, Aleksandra Leligdowicz, Emily R. Siegel, Marina Sirota, Joseph L. DeRisi, Michael A. Matthay, Yumiko Abe‐Jones, Saurabh Asthana, Alexander J. Beagle, Tanvi Bhakta, Sharvari Bhide, Cathy Cai, Saharai Caldera, Carolyn S. Calfee, Sidney Carrillo, Adithya Cattamanchi, Suzanna Chak, Vincent Chan, Nayvin W. Chew, Zachary Collins, Alexis J. Combes, Tristan Courau, Spyros Darmanis, David J. Erle, Armond Esmaili, Gabriela K. Fragiadakis, Jeremy Giberson, Ana Gonzalez, Carolyn M. Hendrickson, Kamir Hiam, Kenneth H. Hu, Billy Huang, Chayse Jones, Norman G. Jones, Kirsten N. Kangelaris, Matthew F. Krummel, Nitasha Kumar, Divya Kushnoor, Tasha Lea, Deanna Lee, David Lee, Kathleen D. Liu, Yale Liu, Salman Mahboob, Jeff Milush, Priscila Muñoz-Sandoval, Nguyễn Hoàng Việt, Gabe Ortiz, Randy Parada, Maíra Phelps, Logan Pierce, Priya A. Prasad, Arjun A. Rao, Sadeed Rashid, Gabriella C. Reeder, Nicklaus Rodriguez, Bushra Samad, Diane Scarlet, Cole Shaw, Alan Shen, Austin Sigman, Matthew H. Spitzer, Yang Sun, Sara Sunshine, Kevin Tang, Luz Torres Altamirano, Jessica Tsui, Erden Tumurbaatar, Kathleen Turner, Alyssa Ward, Michael R. Wilson, Juliane Winkler, Reese Withers, Kristine Wong, Prescott G. Woodruff, Chun Ye, Kimberly Yee, Michelle Yu, Jenny Zhan, Mingyue Zhou, Wandi S. Zhu, Charles Langelier

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldMedicine
TopicCOVID-19 Clinical Research Studies
Canadian institutionsUniversity of Toronto
FundersNational Institute of Allergy and Infectious DiseasesNational Heart, Lung, and Blood InstituteNational Institutes of HealthChina Scholarship CouncilU.S. Department of Health and Human Services
KeywordsCoronavirus disease 2019 (COVID-19)ARDSRNASevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)2019-20 coronavirus outbreakComputational biologyVirologyDNA sequencingRNA-SeqBiologyTranscriptomeMedicineGeneGeneticsLungPathologyGene expressionOutbreak

Abstract

fetched live from OpenAlex

The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a "cytokine storm," we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

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)0.001
metaresearch head score (Gemma)0.108
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.709
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.108
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.003
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 head0.128
GPT teacher head0.479
Teacher spread0.352 · 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.

Study designObservational
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

Citations80
Published2021
Admission routes1
Has abstractyes

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