Cytokine storm dynamics in hantavirus pulmonary syndrome: a multiscale ODE model with Wasserstein early-warning score and application to the 2026 Andes virus outbreak
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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-α, IFN-γ, IL-6, IL-10), VEGF-mediated vascular permeability, and platelets. We derive two reproduction numbers: the viral invasion number ℛ 0 and the immunopathological loop gain ℛ ip . We apply Villani’s hypocoercivity theory and the HWI optimal transport inequality to prove that the spectral gap of the CTL-IFN-γ feedback loop collapses to zero at a critical infected endothelial cell count , providing a computable early-warning threshold. We define a Wasserstein patient stratification score from six clinically observable variables.
Results
At default parameters ( ℛ 0 = 0.396, ℛ ip = 1.875): (1) the DFE is locally asymptotically stable—the virus self-limits—but the CTL-IFN-γ loop has sufficient gain to amplify autonomously once established; (2) the storm-block spectral gap collapses exactly to zero at cells μ L −1 —a threshold attained within hours of infection onset, confirming that immunopathological amplification is essentially unavoidable; (3) rises 1-2 days before P ( t ) reaches clinical threshold, providing an early-warning window; (4) exogenous IL-10 supplementation is the single most effective intervention (predicted 40% reduction in peak permeability), outperforming corticosteroid immunosuppression and ECMO; the combination of all three applied at day 7 reduces peak permeability below the fatal threshold.
Conclusions
This framework predicts that HPS cytokine storm is a structural consequence of ℛ ip > 1 rather than excessive viral load, explaining death after viral clearance. For clinicians managing MV Hondius Andes virus patients today, the model identifies a six-variable triage score and a day-7 IL-10-centred therapeutic window as the highest-priority clinical targets. Full code is open source.
