RAGE has potential pathogenetic and prognostic value in nonintubated hospitalized patients with COVID-19
Bibliographic record
Abstract
BackgroundThe value of the soluble receptor for advanced glycation end-products (sRAGE) as a biomarker in COVID-19 is not well understood. We tested the association between plasma sRAGE and illness severity, viral burden, and clinical outcomes in hospitalized patients with COVID-19 who were not mechanically ventilated.MethodsBaseline sRAGE was measured among participants enrolled in the ACTIV-3/TICO trial of bamlanivimab for hospitalized patients with COVID-19. Spearman's rank correlation was used to assess the relationship between sRAGE and other plasma biomarkers, including viral nucleocapsid antigen. Fine-Gray models adjusted for baseline supplemental oxygen requirement, antigen level, positive endogenous anti-nucleocapsid antibody response, sex, age, BMI, diabetes mellitus, renal impairment, corticosteroid treatment, and log2-transformed IL-6 level were used to assess the association between baseline sRAGE and time to sustained recovery. Cox regression adjusted for the same factors was used to assess the association between sRAGE and mortality.ResultsAmong 277 participants, baseline sRAGE was strongly correlated with viral plasma antigen concentration (ρ = 0.57). There was a weaker correlation between sRAGE and biomarkers of systemic inflammation, such as IL-6 (ρ = 0.36) and CRP (ρ = 0.20). Participants with plasma sRAGE in the highest quartile had a significantly lower rate of sustained recovery (adjusted recovery rate ratio, 0.64 [95% CI, 0.43-0.90]) and a higher unadjusted risk of death (HR, 4.70 [95% CI, 2.01-10.99]) compared with participants in the lower quartiles.ConclusionElevated plasma sRAGE in hospitalized, nonventilated patients with COVID-19 was an indicator of both clinical illness severity and plasma viral load. Plasma sRAGE in the highest quartile was associated with a lower likelihood of sustained recovery and higher unadjusted risk of death. These findings, which we believe to be novel, indicate that plasma sRAGE may be a promising biomarker for COVID-19 prognostication and clinical trial enrichment.Trial RegistrationClinicalTrials.gov NCT04501978.FundingNIH (5T32GM008440-24, 18X107CF6, HHSN261201500003I, R35HL140026, and OT2HL156812).
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".