Preprint Watch 2026-05-21: 1 Clinical Failures Flagged for TNF | Claidex

Q: Why was this TNF preprint flagged?

1 prior Claidex failure claim matched the target-disease mechanism. This preprint models cytokine storm dynamics in hantavirus pulmonary syndrome with explicit TNF-alpha as a node in the inflammatory cascade. The Claidex failure graph for TNF, in particular inb03-soluble-tnf-covid19-ards-futility, records the difficulty of translating TNF blockade to acute respiratory failure outcomes in inflammatory lung injury. The mathematical model here reinforces the multiscale, multi-cytokine character of the storm rather than a single-axis TNF dependency, which aligns with the futility readout for soluble TNF blockade in COVID-19 ARDS. The preprint does not directly contradict the indexed failure; it provides a parsimonious mechanistic frame that is consistent with attenuated TNF-only intervention effect sizes.

Claidex Preprint Watch

doi:10.64898/2026.05.15.26353286

Preprint WatchModerateMay 21st, 2026

Cytokine storm dynamics in hantavirus pulmonary syndrome: a multiscale ODE model with Wasserstein early-warning score and application to the 2026 Andes virus outbreak

des Rochettes, B.

Multiscale ODE model of cytokine storm dynamics in hantavirus pulmonary syndrome identifies TNF-alpha as one node within a multi-cytokine cascade.

Moderate contradiction

1 prior failure

Two documented clinical failures match this mechanism, or a single Phase 3 failure is on record.

This preprint models cytokine storm dynamics in hantavirus pulmonary syndrome with explicit TNF-alpha as a node in the inflammatory cascade. The Claidex failure graph for TNF, in particular inb03-soluble-tnf-covid19-ards-futility, records the difficulty of translating TNF blockade to acute respiratory failure outcomes in inflammatory lung injury. The mathematical model here reinforces the multiscale, multi-cytokine character of the storm rather than a single-axis TNF dependency, which aligns with the futility readout for soluble TNF blockade in COVID-19 ARDS. The preprint does not directly contradict the indexed failure; it provides a parsimonious mechanistic frame that is consistent with attenuated TNF-only intervention effect sizes.

Abstract excerpt

Background. The ongoing Andes hantavirus outbreak linked to the cruise ship MV Hondius (April-May 2026, seven confirmed cases, three deaths, patients hospitalised across six countries including France) highlights the urgent need for mechanistic tools to predict which hantavirus pulmonary syndrome (HPS) patients will progress to fatal cytokine storm. Methods. We present a 14-variable antigen-gated ordinary differential equation (ODE) model integrating viral dynamics, CD8+ cytotoxic T lymphocyte (CTL) expansion, four cytokines (TNF-alpha, IFN-gamma, IL-6, IL-10), VEGF-mediated vascular permeability, and platelets. We derive two reproduction numbers: the viral invasion number R0 and the immunopathological loop gain Rip. We apply Villani's hypocoercivity theory and the HWI optimal transport inequality to prove that the spectral gap of the CTL-IFN-gamma feedback loop collapses to zero at a critical infected endothelial cell count Ic*, providing a computable early-warning threshold. We define a Wasserstein patient stratification score from six clinically observable variables. Results. At default parameters (R0 = 0.396, Rip = 1.875): (1) the disease-free equilibrium is locally asymptotically stable - the virus self-limits - but the CTL-IFN-gamma loop has sufficient gain to amplify autonomously once established; (2) the storm-block spectral gap collapses exactly to zero at Ic* = 2.23 cells/uL, a threshold attained within hours of infection onset, confirming that immunopathological am

Matching Claidex post-mortems

1 of 1 indexed

May 20, 2026INB03 in COVID-19 ARDS: Why a Selective Soluble TNF Strategy Did Not Separate From PlaceboINB03 (XPro1595, pegipanermin)EfficacyMRS 43

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.