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

New 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 host9s 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.