DOI: 10.6084/m9.figshare.27166467
title: Compassionate use of tocilizumab in hantavirus pulmonary syndrome: a pre- and post-study

description: Background and Rationale:Hantavirus Pulmonary Syndrome (HPS) is a severe and often fatal respiratory disease caused by hantavirus infection, with mortality rates reaching up to 60–70%. The disease is characterized by rapid progression to respiratory failure and shock due to a hyperinflammatory response known as a cytokine storm. Currently, there is no specific antiviral treatment for HPS, and management is primarily supportive care in intensive care units (ICUs). Given the high mortality rate and the role of interleukin-6 (IL-6) in the inflammatory process, there is a critical need for effective therapies that can mitigate the severe immune response.<br>Objective:<br>The primary objective of this study is to assess whether the administration of tocilizumab, an IL-6 receptor antagonist, can reduce the mortality rate among patients with HPS by 25% compared to the historical mortality rate without this treatment.<br>Study Design:<br>Type of Study: Pre- and post-intervention study.Study Period: February 2024 to August 2029.Location: Hospital Zonal Bariloche "Ramón Carrillo" in Argentina.Registration: The study is registered with the ISRCTN Registry (ISRCTN72088243).Ethics Approval: Approved by the Ethics Committee for the Evaluation of Protocols of Studies in Human Health Research of the Province of Río Negro (ref: 185470-S-2024).Participants:<br>Inclusion Criteria:<br>Adults aged 18 years or older diagnosed with Hantavirus Pulmonary Syndrome.Diagnosis confirmed through detection of hantavirus-specific IgM antibodies, a four-fold rise in IgG titers, or a positive RT-PCR test for hantavirus RNA.Severity requiring hospitalization.Ability to provide informed consent or have a legal guardian consent on their behalf.Eligible to receive tocilizumab within 24 hours of hospital admission.No known allergies to tocilizumab or its excipients.No severe comorbid conditions that could interfere with study outcomes.Exclusion Criteria:<br>Prior treatment with tocilizumab or related therapies.Severe allergic reactions to tocilizumab.Active or latent severe infections (e.g., tuberculosis, HIV, hepatitis).Pregnancy or breastfeeding.Severe uncontrolled comorbid conditions.Recent live vaccinations within 30 days.Participation in other clinical trials within the last 30 days.Substance abuse or psychiatric illnesses that interfere with compliance.Significant immunosuppression.Intervention:<br>Treatment Administered: A single intravenous dose of tocilizumab at 8 mg/kg (maximum of 800 mg) within the first 24 hours of hospital admission.Standard Care: All participants receive standard medical care for HPS in addition to tocilizumab.Comparison:<br>The study compares the outcomes of participants receiving tocilizumab with historical data from patients with similar demographic and clinical profiles who did not receive tocilizumab.Outcomes:<br>Primary Outcome:<br>Mortality rate at 28 days post-intervention.Secondary Outcomes:<br>Incidence of mechanical ventilation during hospitalization.Duration of mechanical ventilation.Incidence of inotropic support during hospitalization.<br>