Transcriptomic signature on Hantavirus Cardiopulmonary Syndrome patients, reveals an increased interferon response as a hallmark of critically ill patients

Abstract

AbstractNew World hantaviruses are important human pathogens that can cause a severe zoonotic disease called hantavirus cardiopulmonary syndrome (HCPS). HCPS patients can progress quickly to a severe condition with respiratory failure and cardiogenic shock that can be fatal in 30% of the cases. The role of the host’s immune responses in this progression towards HCPS remains elusive. In this study, 12 patients hospitalized with severe HCPS were analyzed using a transcriptome approach combined with clinical laboratory data to gain a better insight into factors associated with a severe clinical course. Patients were further classified in two levels of severity, a first group that required mechanical ventilation and vasoactive drugs (VM+VD) and a second group that also needed ECMO or died (ECMO/Fatal). Their transcriptional profile was compared during acute (early and late) and convalescent phases. Our results showed that overexpression of the interferon response is correlated with a worse (ECMO/Fatal) outcome and an increased viral load and proinflammatory cytokines in the early-acute-phase. This report provides insights into the differences in innate immune activation between severe patients that associates with different clinical outcomes, using a non-biased approximation.Author SummaryHantavirus are rodent-borne zoonotic pathogens that when transmitted to humans cause two diseases: hantavirus renal syndrome in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. The latter, the goal of this work, is a highly lethal disease with a case fatality rate of 30%. Moreover no specific treatment or vaccine is available for this disease. In this study, we analyzed hospitalized HCPS patients with severe disease, to understand how they respond to hantavirus infection. We used a method that can measure every mRNA that is being transcribed in one moment (transcriptome analysis) and thus provide an accurate idea of how cells (specifically peripheral blood mononuclear cells) are responding to infection. The knowledge gained in this study helps us further understand the pathogenesis of this disease and might help us to design specific therapies to treat it.