A blood transcriptome-based analysis of disease progression, immune regulation, and symptoms in coronavirus-infected patients
Bibliographic record
Abstract
COVID-19 patients show heterogeneity in clinical presentation and outcomes that makes pandemic control and strategy difficult; optimizing management requires a systems biology approach of understanding the disease. Here we sought to potentially understand and infer complex disease progression, immune regulation, and symptoms in patients infected with coronaviruses (35 SARS-CoV and 3 SARS-CoV-2 patients and 57 samples) at two different disease progression stages. Further, we compared coronavirus data with healthy individuals (n = 16) and patients with other infections (n = 144; all publicly available data). We applied inferential statistics (the COVID-engine platform) to RNA profiles (from limited number of samples) derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, a subset of integrated blood-based gene profiles (signatures) distinguished acute-like (mimicking coronavirus-infected patients with prolonged hospitalization) from recovering-like patients. These signatures also hierarchically represented multiple (at the system level) parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle observations included PBMC-based increases in cytokine storm-associated IL6, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage showed significantly enhanced TNF, IFN-γ, anti-viral, HLA-DQA1, and HLA-F gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, our analysis revealed overlapping genes associated with potential comorbidities (associated diabetes) and disease-like conditions (associated with thromboembolism, pneumonia, lung disease, and septicemia). Overall, our COVID-engine inferential statistics platform and study involving PBMC-based RNA profiling may help understand complex and variable system-wide responses displayed by coronavirus-infected patients with further validation.
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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 | 0.000 | 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".