TAG-TP #statement on #immunomodulators and host-directed #therapies for #Bundibugyo virus disease (WHO, June 26 '26)

    In the context of prioritization of therapeutics to be included in clinical research for Bundibugyo virus disease (BVD) the Technical Advisory Group on Therapeutics Prioritization (TAG-TP) has begun examining the landscape of immunomodulatory and host-directed new or repurposed agents. 

    Currently, there are no studies in patients characterizing the downstream pathogenesis that follows infection with Bundibugyo virus (BDBV). 

    The available evidence derives mainly from data collected with Ebola virus, specifically Zaire ebolavirus (EBOV) that provides relevant information from animal models and patients, but not sufficient to allow a proper assessment for the selection of immunomodulatory and host-directed candidates for clinical trials in BVD. 

    In addition, it is noted that even corticosteroids have never been tested in a stringent filovirus animal model. 

    For other infectious diseases leading to sepsis or other severe disease evolutions, it is also noted that immunomodulators can be beneficial or detrimental depending on the timing of the administration.

    To allow for a proper scientific evaluation of the different potential interventions, the appropriate timing of administration and the appropriate patient selection for inclusion in large clinical trials, it is imperative to generate quality data on the natural history of BVD from people infected with BDBV. 

    This would likely need to occur at select clinical sites that are adequately equipped to collect and analyze samples from patients with BVD. 

    Suggested data for collection include immune makers associated with inflammation and innate/adaptive immunity, correlative viral load and clinical features, markers of coagulation perturbation and organ/tissue damage. 

    This will help identify biomarkers pertaining to a pro-inflammatory status with co-relation to clinical phenotypes and organ dysfunction.

    Only in this way will it be possible to identify and/or confirm potential pharmacological targets and related potential interventions. 

    Collecting further evidence is paramount to minimizing risks to participants in clinical trials, as, depending on individual patient phenotypes and the status of disease evolution, the administration of some immunomodulatory agents may result in detrimental effects (e.g. on viral replication).

    In addition, some of these clinical investigations may have to be tailored to specific immune phenotypes based on the pharmacological activity of the investigational candidate, but sophisticated biomarker testing should be avoided to ensure implementation of clinical trials at BDBV Treatment Units.

    Lastly, timely availability of data from animal models would also provide evidence to facilitate the identification of the most promising therapies for inclusion in clinical trials.

Source: 

Link: https://www.who.int/news/item/26-06-2026-tag-tp-statement-on-immunomodulators-and-host-directed-therapies-for-bundibugyo-virus-disease

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Use of #tocilizumab for severe #hantavirus pulmonary syndrome: a MEURI case series with contextual comparisons

 

Summary

Background

Hantavirus pulmonary syndrome is a rare zoonotic disease associated with high mortality, acute respiratory failure, shock, capillary leak, and systemic inflammation. Currently, no specific antiviral or immunomodulatory therapy has proven effective for routine clinical use. The current cruise-associated hantavirus outbreak motivated this early descriptive report from an ongoing, larger, pre–post study (ISRCTN72088243). We aimed to describe tocilizumab use under the Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) framework.

Methods

In this descriptive case series at Hospital Zonal de Bariloche Dr Ramón Carrillo, San Carlos de Bariloche, Argentina, patients with laboratory-confirmed severe hantavirus pulmonary syndrome and requiring intensive care unit (ICU) admission or assessment were eligible to receive tocilizumab in addition to standard supportive care, in accordance with the MEURI framework. Tocilizumab was administered to patients within 24 h of ICU admission or ICU-level evaluation as a single intravenous dose of 8 mg/kg, up to a maximum of 800 mg. During this time, five eligible patients could not receive tocilizumab because timely administration was not feasible due to drug unavailability or refractory shock at diagnosis. This case series represents the first report from the larger, ongoing, pre–post study (ISRCTN72088243). The main descriptive outcome was survival to ICU discharge in patients who received tocilizumab and patients who were eligible to receive tocilizumab but did not.

Findings

Between June 1, 2024, and May 5, 2026, 13 patients with laboratory-confirmed hantavirus pulmonary syndrome were evaluated for inclusion after institutional approval of the MEURI protocol. Ten met eligibility criteria for tocilizumab; five received tocilizumab and five did not. In the five eligible non-treated patients, two were diagnosed when they were already in refractory shock, precluding timely administration, and three did not receive tocilizumab because the drug was unavailable when treatment was being considered. Four of five tocilizumab-treated patients survived to ICU discharge. The fifth treated patient died after rapid progression to refractory shock. All five eligible non-treated patients died after ICU admission.

Interpretation

These observations suggest that IL-6 inhibition warrants further evaluation within the MEURI framework or analogous expanded-access frameworks, and, when feasible, collaborative randomised studies with standardised data collection.

Funding

None.

Translations

For the Spanish translations of the abstract see Supplementary Materials section.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00285-9/abstract

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First reported case of #Andes #hantavirus cardiopulmonary syndrome treated with a combination of #favipiravir, #ribavirin, icatibant and baricitinib

 

ABSTRACT

Objectives

To describe the first documented case of Andes virus (ANDV) hantavirus cardiopulmonary syndrome (HCPS) in Spain and the first worldwide use of a therapeutic regime including two antivirals (favipiravir and ribavirin) and two host-directed drugs (baricitinib and icatibant).

Methods

A 69-year-old Spanish man, repatriated following a multinational ANDV outbreak aboard a cruise ship, was managed in a high-level isolation unit. Diagnosis was established by RT-PCR and serology while he was still asymptomatic as part of protocol-driven screening. Under compassionate-use authorisation and written informed consent, the patient received ribavirin (initially intravenous, then switched to oral on day +4), oral favipiravir, subcutaneous icatibant, and oral baricitinib, with serial clinical, laboratory, and radiological monitoring.

Results

Hypoxaemia, bilateral B-lines, thrombocytopenia, lymphopenia, and hyponatraemia developed within 24 hours after diagnosis. The combination regimen was initiated on day 0, and baricitinib was added on day +1, coinciding with the need for high-flow nasal oxygen. Sustained clinical, laboratory, and radiological recovery occurred from day +2 onwards, without progression to invasive ventilation or vasopressors. Mild diarrhoea attributed to ribavirin led to its discontinuation on day +5, shortly after the IV-to-oral switch. Severe recurrent diarrhoea on day +8, attributed to favipiravir, prompted its withdrawal before completion of the planned 10-day course; baricitinib was completed on day +10.

Conclusions

This sentinel case of imported HCPS in non-endemic Europe was managed with, to our knowledge, the first reported combined antiviral and host-directed regimen for this syndrome and the first reported use of favipiravir in a patient with hantavirus infection. The favourable outcome supports prospective evaluation of antiviral combinations and adjunctive immunomodulation within international preparedness protocols.

Source: 

Link: https://www.clinicalmicrobiologyandinfection.org/article/S1198-743X(26)00310-1/fulltext

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Host #Immunomodulatory Interventions in Severe #Influenza

 

Abstract

Currently, no immunomodulatory agents have been conclusively shown to benefit severe influenza. The World Health Organization conditionally advises against the use of systemic corticosteroids, macrolides, plasma therapy, mechanistic target of rapamycin inhibitors, and nonsteroidal anti-inflammatory drugs for such patients. High-dose systemic corticosteroids may increase mortality and morbidity in severe influenza; the potential of low-dose corticosteroids merits further study given survival benefits in patients with severe coronavirus disease 2019 (COVID-19). Passive immunotherapy using convalescent plasma or intravenous immunoglobulin (IVIG) from healthy donors has not proven effective, suggesting that future research should focus on hyperimmune plasma or IVIG from recent infections. An open-label randomized controlled trial (RCT) found that a triple combination of oseltamivir, clarithromycin, and naproxen improved outcomes in severe influenza. One RCT has indicated that sirolimus with corticosteroids can expedite liberation from mechanical ventilation and reduce viral load, warranting larger trials of sirolimus alone. In contrast, adding macrolides or nitazoxanide has not consistently improved clinical outcomes. Promising evidence exists for anti-C5a antibodies in COVID-19, while case reports hint that intravenous N-acetylcysteine may benefit severe influenza pneumonia. Observational data on statins remain conflicting. Further studies on COX-2 inhibitors in combination with antivirals and other immunomodulators are needed. Mycophenolic acid, pamidronate, and peroxisome proliferator-activated receptor gamma agonists are low priorities due to toxicity concerns. Research into human mesenchymal stromal cells and herbal medicine remains inconclusive. Overall, these findings support large-scale trials to validate promising results and address limitations in small studies. Treatment of severe influenza requires a multidisciplinary approach that integrates antiviral and immunomodulatory strategies. Clarifying these roles may enhance patient outcomes.

Source: Journal of Infectious Diseases, https://academic.oup.com/jid/article/232/Supplement_3/S262/8287912

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