Longitudinal gene expression analysis in COVID-19 sepsis highlights dynamic immune, cellular, and metabolic dysfunction in high severity patients
Bibliographic record
Abstract
COVID-19 patients experience dynamic changes in immune and cellular function over time, similar to that in sepsis. However, there is insufficient research investigating, at the gene expression level, the mechanisms that become activated or suppressed over time as patients deteriorate or recover. This has potential prognostic and therapeutic implications. In this longitudinal study, 300 whole blood samples were analyzed from 128 adult patients throughout their COVID-19 hospitalization. Transcriptome sequencing (RNA-Seq), differential gene expression analysis, pathway enrichment, and drug-gene set enrichment analysis were performed to elucidate key mechanisms for therapeutic targeting during six distinct disease phases through the COVID-19 trajectory. Adaptive immune dysfunction, inflammation, and metabolic dysregulation were most pronounced during phases with higher disease severity. Hemostatic dysregulation was present early and persisted throughout the disease course, in contrast to an early antiviral response and late heme metabolism activity. Drug-gene set enrichment analysis predicted repurposed medications for potential use, including platelet inhibitors, antidiabetic medications, and dasatinib. Disease phases had distinct transcriptional signatures and were highly correlated to previously developed sepsis endotypes, indicating that severity and disease timing were significant contributors to heterogeneity observed in COVID-19 sepsis. These findings provide an opportunity for better prognostication of patients and potential time-dependent personalized treatments.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".