Baloxavir marboxil use for critical human infection of avian influenza A H5N6 virus

Abstract

AbstractBackgroundRecent increase in human infections of highly pathogenic avian influenza H5N6 virus and its high mortality have raised concerns.MethodsTo analyze evolution of outcomes, longitudinal clinical data and specimens were collected from five patients infected with H5N6 virus after admission. All patients received antiviral treatment either sequentially or in combination of oseltamivir with baloxavir. Severity of illness, and viral load in sputum, urine and blood, and cytokine levels in serum and sputum were serially analyzed.ResultsWhen delayed oseltamivir showed poor effects on high respiratory viral load, baloxavir was prescribed and viral load had a rapid reduction. All patients developed acute respiratory distress syndrome (ARDS) and sepsis within one week after disease onset, three patients died eventually. Nonsurvivors had more severe preexisting condition, extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response. Grouped by delta SOFA on the sample collection date, serum levels of IL-1α, IL-1β, IL-1RA, MIF, Mig, MIP-1α, IFN-γ, IL-12p40, IL-16, IL-18, IL-2Rα, IL-6, basic FGF, G-CSF, HGF, M-CSF, SCF were identified as indicator cytokines reflecting sepsis progression; and sputum levels of IL-18, IL-6, HGF, M-CSF were indicators of ARDS progression. Comparisons of cytokine levels before, during and after baloxavir treatment suggested that, baloxavir may also reduce a few indicator cytokines in sputum and serum that related to viral load and multi-organ dysfunction.ConclusionsBaloxavir can effectively reduce viral load and few proinflammatory cytokines associated with deterioration. However, disease outcome is determined by severity of preexisting conditions and multi-organ dysfunction.Highlights(1)Baloxavir potently decreased viral load in avian influenza H5N6 human infections.(2)Preexisting conditions, extrapulmonary dysfunction and systemic inflammation determined prognosis of H5N6 patients.(3)Indicator cytokines in sputum and serum reflecting ARDS and sepsis progression respectively, were identified in H5N6 patients.