A Decade of Chronic #Hepatitis E #Treatment: #Ribavirin Effectiveness, Safety, and the Association of Torque Teno Virus Load With Treatment Outcomes

 

Highlights

    • Ribavirin achieved 81% SVR in immunocompromised patients with chronic HEV.

    • Adverse events occurred in 56% and led to discontinuation in 17%.

    • Ribavirin dose reduction was associated with failure to achieve SVR.

    • Higher baseline HEV RNA levels were associated with non-SVR.

    • Baseline TTV load showed a nonsignificant trend toward higher levels in non-SVR patients.

Abstract

Background

Hepatitis E virus (HEV) affects immunocompromised individuals. Unlike immunocompetent hosts, who rarely develop chronic infection, up to two-thirds of immunocompromised patients progress to chronicity. Ribavirin is the recommended antiviral therapy, yet predictors of sustained virological response (SVR) remain unclear. Torque Teno Virus (TTV), a marker of immunosuppression, has been proposed as a potential predictor of viral clearance.

Objectives

We evaluated ribavirin treatment outcomes and adverse effects in immunocompromised patients with HEV infection, and assessed whether TTV load predicts SVR.

Study Design

A retrospective cohort study was conducted at the University Medical Center Groningen including solid organ transplant recipients (SOTR) and haematology patients treated with ribavirin for HEV infection between 2010 and 2022. Clinical data and stored serum samples were analysed to determine infection duration and TTV load at treatment initiation and after three months. TTV loads in treated patients were compared with TTV loads of transplant recipients who spontaneously cleared HEV.

Results

Fifty-two patients received ribavirin; 27 had confirmed chronic infection. SVR was achieved in 81% of chronic cases. Adverse events occurred in 56%, leading to dose reduction in 25% and discontinuation in 17%. Non-SVR was associated with ribavirin dose reduction, lower mean daily dose, higher baseline HEV RNA, and lower ALT. Baseline TTV load showed a nonsignificant trend toward higher levels in non-SVR patients. TTV loads did not differ between treated patients and spontaneous clearers.

Conclusions

Ribavirin is effective for chronic HEV, but treatment-limiting toxicity is common. Adequate dosing appears critical for achieving SVR. TTV load did not reliably predict treatment outcome, underscoring the need for further research into immunological and virological predictors of response.

Source: 

Link: https://doi.org/10.1016/j.jcv.2026.106003

_____

Notes from the Field: #Clinical Characteristics of Patients with #Ebola Disease Caused by #Bundibugyo Virus — #Uganda, 2026

 

Summary

    ° What is already known about this topic?

        § Clinical and epidemiologic descriptions of Bundibugyo virus disease (BVD) are rare; case-fatality rates in previous outbreaks have ranged from 32% to 55%. Effective treatments have not been described.

    ° What is added by this report?

        § Among the first 21 cases (20 confirmed; one probable) in the 2026 Uganda BVD outbreak, 18 were admitted to the Mulago National Referral Hospital Ebola Treatment Unit (ETU). Among these 18, all had elevated liver enzymes, hypoalbuminemia, and hyponatremia on ETU admission. All 18 received treatment with remdesivir through an off-label, compassionate-use protocol. Among 20 confirmed cases, 18 (90%) patients survived; two deaths occurred among patients with confirmed cases whose infections were recognized late. Seeking care promptly might have reduced the number of deaths.

    ° What are the implications for public health practice?

        § Communicating with the public about the benefits of seeking health care promptly when BVD is suspected might improve patient outcomes. Clinical trials of remdesivir for patients with BVD might be warranted.

Abstract

    Ebola disease is a viral hemorrhagic fever caused by viruses of the genus Orthoebolavirus. Bundibugyo virus (Orthoebolavirus bundibugyoense), first identified in 2007 in Bundibugyo District, Uganda, is one of four orthoebolaviruses known to cause Ebola disease in humans; only two previous Bundibugyo virus disease (BVD) outbreaks have been documented. Transmission occurs through direct contact with infectious blood or other body fluids. Common signs and symptoms include fever, abdominal pain, diarrhea, vomiting, weakness, and bleeding from orifices and injection sites. Case-fatality rates (CFRs) among confirmed cases in the two previous outbreaks ranged from 32% to 55% (1,4). No licensed vaccine or specific treatment is available for BVD; clinical management is primarily supportive. On May 15, 2026, the Uganda Ministry of Health confirmed an outbreak of BVD imported from the neighboring Democratic Republic of the Congo (DRC). On August 26, 2026, the outbreak was declared over in Uganda with 20 confirmed BVD cases and one probable case reported, although the outbreak in DRC is ongoing. This report describes the clinical and epidemiologic characteristics of all 21 cases. This activity was reviewed by CDC, deemed not research, and conducted consistent with applicable federal law and CDC policy.*

Source: 

Link: http://dx.doi.org/10.15585/mmwr.mm7535a2

____

Emergence and spread of NA-I223V and NA-S247N double-mutant #H1N1pdm09 #influenza viruses with reduced #oseltamivir susceptibility in the #Netherlands and beyond, 2023 to 2026

 

Abstract

In 2023/24, A(H1N1)pdm09 influenza viruses with neuraminidase (NA)-S247N emerged in NA-clade C.5.3.3 carrying NA-I223V, spread internationally, then faded. Such double mutants reappeared sporadically in 2024/25. They expanded again in 2025/26 in NA-clade D.3 viruses carrying NA-S247N after acquiring NA-I223V in Europe – notably Spain, the Netherlands, Finland and France, and beyond. Dutch double mutants from both seasons showed median 12- and 13-fold reduced inhibition by oseltamivir. These findings underscore the need for ongoing genomic and phenotypic monitoring of antiviral susceptibility.

© Creative Commons License. This work is licensed under a Creative Commons Attribution 4.0 International License.

Source: 

Link: https://doi.org/10.2807/1560-7917.ES.2026.31.36.2600733

____

Updated #H1N1pdm09 #influenza virus #ferret infection #model permits refined #antiviral #assessment using aerosol inhalation challenge

 

Abstract

Seasonal influenza viruses continue to pose a significant threat to human health. As influenza viruses exhibit sustained genetic drift, it is imperative that animal studies utilize challenge strains that reflect contemporary, currently circulating viruses when evaluating pathogenicity, viral tropism, transmissibility, and antiviral sensitivity to better inform public health responses. Ferrets are considered the gold-standard small animal model for assessing currently circulating influenza viruses. Seasonal influenza A(H1N1)pdm09 viruses replicate well in both the upper and lower respiratory tract of ferrets, providing an important model for developing improved vaccination and therapeutic strategies; however, many of these studies have relied on a 2009 virus isolate. Utilising representative influenza A(H1N1)pdm09 virus strains from 2009 to 2022, we explored virus replication kinetics and lung pathogenesis in ferrets following intranasal inoculation with these contemporary strains. Our results revealed strain specific differences, with greater lung viral loads and pathogenesis following inoculation with A/Sydney/5/2021 compared to other strains. Efficient transmissibility of A/Sydney/5/2021 virus to naïve recipients was also observed following both contact and airborne exposure to infected donor ferrets. To refine this updated model, we performed side-by-side evaluation of oseltamivir antiviral efficacy following traditional intranasal or aerosol inhalation influenza challenges. Pre-treatment with oseltamivir demonstrated greater reductions in viral shedding from the upper respiratory tract than post-infection treatment of ferrets infected by aerosol inhalation, while the intranasal route showed reduced oseltamivir efficacy independent of the timing of antiviral treatment. These findings provide the basis for using an updated A(H1N1)pdm09 challenge virus for ferret studies as an alternative to the commonly used, but now less relevant 2009 early pandemic viruses. It also highlights how different methods of virus inoculation can influence outcomes of ferret antiviral studies, with an aerosol challenge model able to demonstrate differences between therapeutic and prophylactic treatments, which were not apparent with an intranasal challenge model.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014604

____

#Report on #influenza viruses received and tested by the #Melbourne #WHO Collaborating Centre for Reference and Research on Influenza during 2025

 

Abstract

As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne (the Centre) received 13,817 human influenza-positive samples during 2025. Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. Of the 13,817 samples received or processed, influenza A(H1N1)pdm09 viruses predominated, accounting for 46.1% of samples, compared to 21.2% for A(H3N2) viruses and 19.5% for influenza B viruses; one influenza C virus was received. Among viruses analysed at the Centre, the majority of A(H1N1)pdm09 (> 99%) and influenza B (98%) viruses were antigenically similar to their respective WHO recommended vaccine strains for the Southern Hemisphere in 2025. In contrast, only 43% of A(H3N2) viruses were antigenically similar to their respective WHO recommended vaccine strains. Of 3,307 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, 37 A(H1N1)pdm09 viruses showed highly reduced inhibition by oseltamivir and no influenza viruses tested showed highly reduced inhibition by zanamivir. Of 5,080 samples with sequencing of the polymerase acidic (PA) gene, no genetic markers associated with highly reduced susceptibility to baloxavir marboxil were identified.

Source: 

Link: https://ojs.cdi.cdc.gov.au/index.php/cdi/article/view/3489

____

#Nirmatrelvir–ritonavir targeting viral #persistence in post-COVID-19 condition (long #COVID) in the #USA (RECOVER-VITAL): a randomised, double-blind, placebo-controlled, phase 2 trial

 

Summary

Background

Post-acute sequelae of SARS-CoV-2 infection, more commonly known as long COVID, has emerged as a major health problem. The pathogenesis of long COVID is unknown, but among the leading hypotheses is viral persistence. We aimed to investigate whether the use of the SARS-CoV-2 antiviral nirmatrelvir–ritonavir improved long COVID symptoms.

Methods

We conducted a double-blind, placebo-controlled, randomised trial involving adults who had developed persistent symptoms (≥12 weeks) associated with three major symptom phenotypes (cognitive, autonomic, or exercise) after acute SARS-CoV-2 infection at 69 US sites. Participants were eligible if they were 18 years or older and had a previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization. Eligible participants were also required to have either at least two moderate symptoms from the same phenotype or one severe phenotype-associated symptom, as identified with the Cluster Targeted COVID-19 Symptom Questions. Participants were randomly allocated in a double-blind manner in a 1:1:1 ratio using permuted blocks of size 30 to receive either 15 days of active intervention followed by 10 days of placebo (300 mg nirmatrelvir–100 mg ritonavir twice daily, then 100 mg ritonavir–placebo); 25 days of active intervention (300 mg nirmatrelvir–100 mg ritonavir twice daily); or 25 days of placebo–ritonavir (100 mg ritonavir–placebo). A clinically significant change in patient-reported outcomes at day 90 comprised the primary endpoint: Patient-Reported Outcomes Measurement Information System Cognitive Function Short Form 8a, Orthostatic Hypotension Questionnaire question 1, and a modified version of the DePaul Symptom Questionnaire Post-Exertional Malaise short form. Secondary outcomes were phenotype-specific performance measures. The study was registered at ClinicalTrials.gov (NCT05595369) and is complete.

Findings

Between July 27, 2023, and Sept 6, 2024, 1207 individuals were screened. Of these, 964 were randomly allocated and 959 participants, excluding four participants who were later found ineligible and one who did not initiate treatment, were enrolled in the three phenotypes: 332 to cognitive, 334 to autonomic, and 332 to exercise. In the 959 participants in the mITT population, 643 (67%) self-reported as female, 314 (33%) were male, and two participants had a sex of unknown or undifferentiated; 750 (78%) were White; and 108 (11%) were Hispanic, Latino, or Spanish. The median age was 49 years (IQR 38–59). No statistically significant benefits were observed for any phenotype for primary endpoints. For the cognitive phenotype, adjusted differences compared to placebo were 3·2% (95% CI –10·4 to 16·8, p=0·65) for the 25-day regimen and –2·2% (–15·5 to 11·1, p=0·74) for the 15-day regimen. For the autonomic phenotype, adjusted differences were –6·4% (–18·5 to 5·7, p=0·30) for the 25-day regimen compared to placebo and –0·1% (–12·5 to 12·3, p=0·99) for the 15-day regimen compared to placebo. For exercise, adjusted differences were –7·8% (–19·5 to 3·8, p=0·19) for the 25-day regimen compared to placebo and 0·9% (–11·4 to 13·2, p=0·88) for the 15-day regimen compared to placebo. There were no differences in secondary endpoints, and no safety signals were observed; there were no deaths, and 52 serious adverse events occurred in 42 (4%) of 963 participants over the course of the study.

Interpretation

Nirmatrelvir–ritonavir for 15 days or 25 days showed no evidence of benefit in long COVID in any of the three phenotypes studied. These findings suggest additional approaches to measuring the symptom burden and treating Long COVID are needed.

Funding

National Institutes of Health.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00406-8/fulltext

____

Evaluating the #impact of #antiviral post-exposure #prophylaxis for health-care workers during #orthoebolavirus outbreaks: a modelling study

 

Summary

Background

Orthoebolavirus outbreaks place health-care workers (HCWs) at substantial risk, and HCW illness or death can weaken response capacity. The 2026 Bundibugyo virus outbreak in DR Congo highlights the need for deployable countermeasures when species-specific vaccines are unavailable. With candidate antivirals under evaluation, we aimed to estimate the impact of HCW-targeted antiviral post-exposure prophylaxis (PEP) across different readiness, disruption, and allocation scenarios.

Methods

We adapted a previously published stochastic branching-process model of orthoebolavirus transmission, representing health care, community, and funeral transmission; time-varying non-pharmaceutical interventions; and HCW-targeted PEP. The model was calibrated to two historical outbreaks using sequential approximate Bayesian computation: the 2013–16 west Africa epidemic, to define a high-burden, reasonable worst-case scenario archetype (west Africa-like archetype); and the 2018–20 North Kivu and Ituri outbreak in eastern DR Congo, to define an archetype with longer transmission under conflict-related response disruption (DR Congo-like archetype). The primary outcome was HCW deaths averted. For both archetypes, we simulated three antiviral deployment readiness scenarios (scenario 1: 100% coverage on day 0; scenario 2: scaled up to 80% coverage over 180 days; and scenario 3: scaled up to 50% coverage over 1 year) and compared their impact on HCW deaths with a scenario of no antiviral. For the DR Congo-like archetype only, we simulated four disruption scenarios: no antiviral PEP, ideal delivery (100% coverage and no dosing delay), delayed dosing with coverage preserved, and delayed dosing with delayed coverage. As a secondary outcome, we assessed number of PEP doses required per HCW death averted under different allocation scenarios.

Findings

At baseline (no antiviral PEP), cumulative HCW deaths reached a median of 553 (IQR 208–983) in the west Africa-like archetype by week 60, compared with 61 (19–125) in the DR Congo-like archetype by week 80. Assuming 80% efficacy and 80% coverage with antiviral PEP in the same timeframe in a central analysis, cumulative HCW deaths fell to 200 (68–349; equivalent reduction of 64% [63–66] relative to baseline) in the west Africa-like archetype and 22 (10–44; equivalent reduction of 64% [60–68]) in the DR Congo-like archetype. Under different scenarios of deployment readiness at 80% antiviral efficacy, the median reduction in HCW deaths compared with no PEP was 80% (95% CrI 79–81) in the west Africa-like archetype and 80% (76–84) in the DR Congo-like archetype for scenario 1; 60% (57–62) and 52% (41–58), respectively, for scenario 2; and 19% (16–22) and 22% (7–29), respectively, for scenario 3. In the DR Congo-like operational disruption analyses, an ideal scenario (PEP delivered at 100% coverage without a delay after exposure) averted 83% (79–87) of HCW deaths compared with no antiviral; maintaining 100% coverage but introducing delayed dosing (1–5 days post-exposure) reduced this finding to 50% (40–55) compared with no antiviral. Delayed coverage and dosing resulted in only 35% (25–47) of the ideal scenario impact. At 80% antiviral efficacy with same-day dosing, targeted allocation of recognised high-risk exposures (such as personal protective equipment breaches or direct body-fluid contact) required 44 doses (95% Crl 43–44) per HCW death averted versus 109 doses (85–161) with broad allocation.

Interpretation

HCW-targeted antiviral PEP could substantially reduce HCW deaths during orthoebolavirus outbreaks if efficacious antivirals can be delivered rapidly and high operational coverage is maintained. Comparisons of antiviral use cases and alternative response investments are needed to determine how resources can best support outbreak response.

Funding

Gilead Sciences, UK National Institute for Health and Care Research, Oxford Martin School, Miller Institute, EU Global Health EDCTP3, and Coalition for Epidemic Preparedness Innovations.

Translations

For the French and Swahili translations of the abstract see Supplementary Materials section.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00437-8/fulltext?rss=yes

____

COMbination #therapy with #baloxavir and #oseltamivir 1 for hospitalized patients with #influenza: The pragmatic COMBO 1 randomized controlled trial

 

Abstract

Background

COMBO 1 compared time to cessation of viral shedding (TCVS) among hospitalized influenza patients treated with oseltamivir plus a single dose of baloxavir vs. oseltamivir alone.

Methods

In a quadruple-blinded, placebo-controlled parallel group multicenter randomized controlled trial, hospitalized patients with laboratory-confirmed influenza were randomly enrolled in a 1:1 ratio to Group 1 (oseltamivir+placebo) or Group 2 (oseltamivir+baloxavir). All patients were treated with oseltamivir for 5 days; one dose of baloxavir or placebo was given in identical capsules. Primary efficacy and safety outcomes were TCVS by virus titer with qCulture TCID50 agglutination and 30-day severe adverse event (SAE) rate, respectively. Secondary virology, clinical, and safety outcomes were assessed. Continuous and categorical data were analyzed with Wilcoxon Rank-Sum and Fisher’s Exact Tests, respectively.

Results

14 participants were randomized and received study drug (Group 1: n=6, Group 2: n=8); the study was stopped early due to slow accrual. Baseline characteristics were balanced. Median TCVS with qCulture was 53.3 hours in Group 1 and 25.3 hours in Group 2 (p=0.13). 30-day overall SAE rates were 16.7% and 12.5%, respectively. All patients achieved negative qCulture. Median TCVS with quantitative PCR (RT-qPCR) was 115.6 and 34.4 hours (p=0.24); % achieving viral negative by RT-qPCR was 33.3% and 75.0% (p=0.28), respectively.

Conclusions

Combination therapy with oseltamivir and a single dose of baloxavir was inconclusive with non-significant trends towards shorter median TCVS vs. monotherapy with oseltamivir in hospitalized patients with influenza. Interpretation is limited by small sample size and early termination.

Source: 

Link: https://journals.sagepub.com/doi/10.1177/13596535261479944

____

A randomised, open-label clinical study on the efficacy of #baloxavir marboxil and #oseltamivir for post-exposure #prevention of #influenza in a #hospital setting: a study protocol

 

Abstract

Introduction 

Healthcare settings are high-risk environments for the transmission of respiratory viruses. Effective strategies to prevent hospital-acquired influenza, particularly post-exposure prophylaxis for close contacts (CCs), are urgently needed. This study aims to assess the effectiveness of baloxavir marboxil (baloxavir) and oseltamivir in preventing influenza virus infection among CCs who have been exposed to confirmed influenza cases and are unable to be immediately isolated in the hospital ward.

Methods and analysis 

This multicentre, randomised, open-label, parallel-controlled trial involves hospitalised patients with laboratory-confirmed influenza (index patients) and their CCs. CCs will be randomised into three groups: baloxavir marboxil, oseltamivir or placebo. Baloxavir (40 mg or 80 mg for ≥80 kg) will be administered as a single dose on day 1, while oseltamivir (75 mg) will be given once a day for 5 days. CCs will be monitored for influenza-like symptoms, with respiratory samples collected for rapid antigen test or reverse-transcription PCR testing at baseline, day 5±1 and day 10±1 or earlier if symptoms develop. The primary outcome is the 5-day incidence of clinical influenza, defined as laboratory-confirmed infection with concurrent fever and at least one respiratory symptom. Secondary outcomes will include the 5-day incidence of laboratory-confirmed influenza, the 10-day incidence of clinical influenza and the percentage of CCs infected with resistance-associated treatment-emergent influenza variants.

Ethics and dissemination 

The study has been approved by the Clinical Research Ethics Committee of China-Japan Friendship Hospital (2024-KY-401). The results of the study will be submitted for publication in a peer-reviewed journal with online accessibility. The full protocol, de-identified participant data and statistical code will be openly available in a public repository within 12 months after trial completion.

Trial registration number NCT06762587. 

https://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.

Source: 

Link: https://bmjopen.bmj.com/content/16/8/e118748

____

#Treatment of #CCHF with supportive care, #favipiravir, and avatrombopag

 

Abstract

We report a severe Crimean-Congo Hemorrhagic Fever case treated with favipiravir and avatrombopag in a high-level isolation unit. This multimodal approach was associated with rapid platelet recovery, reduced transfusion requirements, and viral clearance. Combining targeted antivirals with thrombopoietin receptor agonists represents a promising strategy for managing severe CCHF coagulopathy.

Source: 

Link: https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciag415/8765585?redirectedFrom=fulltext

____

#Maraviroc Inhibits #SARS-CoV-2 Through Variant-Dependent Effects on Viral Entry and #Mpro Activity Using Single-Round Infectious Particle and Virus-like Particle Models

 

Abstract

Maraviroc (MVC), a CCR5 antagonist, has been proposed as a potential antiviral agent against SARS-CoV-2; however, its mechanism of action across viral variants remains unclear. Here, we evaluated the antiviral activity of MVC against SARS-CoV-2 wild-type (WT) and Omicron BA.1 variants using single-round infectious particles (SRIPs), virus-like particles (VLPs), and cell-based assays, with a focus on its impact on viral entry and Mpro function. MVC potently inhibited infection of both WT and BA.1 SRIPs in Vero E6 cells, exhibiting EC50 values of 0.0065 μM and 0.016 μM, respectively. Time-of-addition assays revealed that MVC primarily targets the early phase of infection, with the strongest inhibition observed at the viral entry stage, while moderate effects were detected during attachment and post-entry stages. Fluorescence-labeled VLP imaging demonstrated distinct entry pathways, with WT predominantly entering via plasma membrane fusion and BA.1 via endocytosis, independent of cell type. MVC altered WT-VLP trafficking by promoting internalization and lysosomal localization, whereas it had minimal impact on BA.1 internalization. In spike-mediated cell–cell fusion assays, MVC preferentially inhibited WT spike-driven syncytium formation but showed limited effects on BA.1 or BA.4 fusion, while more effectively reducing Omicron spike-mediated binding. At the post-entry stage, MVC inhibited SARS-CoV-2 main protease (Mpro) activity, with BA.1 Mpro (P132H) exhibiting greater sensitivity (IC50 = 0.496 µM) than WT (1.869 µM). Collectively, these findings demonstrate that MVC exerts variant-dependent antiviral effects by targeting viral entry, modulating trafficking pathways, and inhibiting Mpro activity. This study highlights MVC as a multi-stage inhibitor with differential efficacy against SARS-CoV-2 variants, providing insights into its potential therapeutic application.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/911

____

#Lassa fever and Argentine hemorrhagic fever #treatment in guinea pigs using broad-spectrum cap-dependent #endonuclease #inhibitors

 

ABSTRACT

The class Bunyaviricetes encompasses several highly pathogenic viruses that cause lethal hemorrhagic fevers. Due to their limited prevention and treatment options and high pathogenicity, these viruses require handling in biosafety level-4 facilities. Within the bunyaviruses, arenaviruses are particularly notable for their pathogenicity and ability to cause severe hemorrhagic disease in humans. The cap-dependent endonuclease (CEN) is a unique and crucial enzyme involved in the replication cycle of these viruses. As humans do not possess a similar enzyme, CEN represents an ideal target for antiviral drug development with reduced risk of side effects. Recently, we identified a promising CEN inhibitor (CENi) demonstrating potent inhibition of virus replication. In this manuscript, we demonstrate the successful therapeutic efficacy of CENis against Lassa fever and Argentine hemorrhagic fever virus infections in guinea pig models of lethal hemorrhagic fever. In addition, we identified several CENis with antiviral activity against other highly pathogenic arenaviruses. These findings further support the potential of CENis as therapeutic agents for arenavirus infections that cause severe and often lethal hemorrhagic fever. Collectively, our results suggest that CENis are promising candidates for pan-arenavirus therapy and may also have broader utility against other CEN-containing viruses for which no approved antiviral treatments currently exist.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.00880-26

____

The association of empirical #treatment with #oseltamivir with the #outcome of critically ill patients admitted with severe acute respiratory illness (#SARI)

 

Abstract

Objective

Neuraminidase inhibitors (NAIs) are widely used empirically in critically ill patients with suspected influenza; however, their effect on mortality remains uncertain. This multicenter study evaluates the association between empirical treatment with oseltamivir and the outcome of critically ill patients with Severe Acute Respiratory Infection (SARI) admitted to the Intensive Care Unit (ICU).

Methods

This was a retrospective cohort study conducted in the ICUs of four hospitals in Saudi Arabia, involving adult patients with SARI from September 2012 to December 2018. Data collected were: demographics, comorbidities, clinical presentation, and outcomes among patients treated with oseltamivir and those who were not. The primary outcome was 90-day mortality. The association of oseltamivir and mortality was evaluated adjusting for propensity score.

Results

During the study period, 456 patients with SARI were included in the study, 301 were treated with empirical oseltamivir within a median of 1 day from presentation (interquartile range, 0-1 day) and a median of 4 days after symptom onset, while 155 patients were not. No significant differences were observed in baseline characteristics between the two groups. Of the included patients, 334 (73%) were tested for influenza using PCR, and 87 (26%) had a confirmed diagnosis of influenza. Patients on oseltamivir were less likely to require rescue oxygen therapy (22.9% vs. 34.8%, p=0.007), and had shorter hospital stay (20 days vs. 27 days, p=0.01). Patients treated with oseltamivir had significantly reduced 90-day mortality on adjusted analyses (aOR: 0.87, 95% CI: 0.81-0.94, p=0.0002). Subgroup analysis revealed that the association with reduced mortality extends to patients >70 years old (aOR: 0.94, 95% CI: 0.89-0.99, p=0.02) and those with negative influenza tests (aOR: 0.81, 95% CI: 0.79, 0.84, p<0.0001).

Conclusion

Among critically ill patients with SARI, empirical treatment with oseltamivir was associated with lower mortality. These results add to the body of evidence suggesting clinical benefits of oseltamivir in managing critically ill patients with influenza-like illnesses.

Source: 

Link: https://journals.sagepub.com/doi/10.1177/20503121261478401

____

Effectiveness of #Oseltamivir in Hospitalized #Children With Laboratory-Confirmed #Influenza, 2014-2023

 

Key Points

    ° Question: 

        § Does oseltamivir treatment reduce risk of intensive care unit (ICU) admission and hospital length of stay among pediatric patients hospitalized with influenza?

    ° Findings:  

        § Using a cohort study from a population-based surveillance network in 13 states across 8 influenza seasons, oseltamivir treatment was found to decrease both the likelihood of ICU admission and hospital length of stay among pediatric patients hospitalized with laboratory-confirmed influenza.

    ° Meaning:  

        § These findings support the current national recommendations from the American Academy of Pediatrics, US Centers for Disease Control and Prevention, and Infectious Diseases Society of America that recommend antiviral treatment for children hospitalized with laboratory-confirmed influenza.

Abstract

Importance  

National organizations recommend antiviral treatment for hospitalized children with influenza; however, use in this setting has recently declined. Studies of oseltamivir effectiveness in children are limited by misclassification bias, unknown symptom onset date, and incomplete capture of antiviral use prior to admission.

Objective  

To assess the association between oseltamivir receipt and intensive care unit (ICU) admission and hospital length of stay (LOS) among pediatric influenza-associated hospitalizations.

Design, Setting, and Participants  

This cohort study used data that were obtained from the Influenza Hospitalization Surveillance Network (FluSurv-NET), which conducts US population-based surveillance for laboratory-confirmed influenza hospitalizations for all ages across 13 states. The study data include seasons 2014 to 2015 through 2022 to 2023, excluding 2020 to 2021. Participants included children aged younger than 18 years who were hospitalized with laboratory-confirmed influenza and for whom a respiratory symptom onset date was available. These data were analyzed from October 2024 through May 2026.

Exposures  

Oseltamivir receipt as a time-dependent exposure.

Main Outcome(s) and Measure(s)  

The primary outcome was time from symptom onset to ICU admission. Secondary outcome was time from admission to discharge (LOS). Adjusted Cox proportional hazard models (aHR) with oseltamivir receipt as a time-dependent exposure were used.

Results  

After exclusions, 6044 influenza cases were included in the primary ICU analysis, of whom 4240 (70.2%) received oseltamivir, and 7103 cases were included in the secondary LOS analysis, of whom 5746 (80.9%) received oseltamivir. In the ICU analysis, the median (IQR) age was 3 (1-7) years, 3382 (56%) were male and 3721 (44%) were female, and 2937 (49%) had 1 or more medical comorbidity—the most common of which was asthma in 1547 children (26%). In adjusted models, compared with untreated children, oseltamivir treatment reduced the hazard of ICU admission (aHR, 0.69; 95% CI, 0.60-0.80) and shortened LOS (analyzed as hazard of hospital discharge; aHR, 1.13; 95% CI, 1.06-1.21).

Conclusions and Relevance  

In this cohort of children hospitalized with influenza, oseltamivir treatment was significantly associated with a reduced risk of ICU admission by 31% and decreased hospital LOS. These findings demonstrate the benefits of oseltamivir receipt and support current national recommendations for oseltamivir treatment as soon as possible in children hospitalized with suspected or laboratory-confirmed influenza.

Source: 

Link: https://jamanetwork.com/journals/jamapediatrics/fullarticle/2852671

____

Detection and characterization of #antiviral #resistant viruses during the #influenza season of 2024–25

 

ABSTRACT

During the high severity season of 2024–25, CDC with public health partners sequenced and analyzed genomes of >10,000 influenza viruses for antiviral resistance markers. Available sequence-flagged and representative viruses were tested with antivirals using in vitro assays. In the US, three oseltamivir-resistant A(H3N2) viruses had treatment-emergent neuraminidase (NA) mutations, either E119V or R292K. Oseltamivir-resistant A(H1N1)pdm09 viruses with NA-H275Y were detected in 15 states, albeit at a low frequency (0.53%). They belonged to several phylogenetic groups, with hemagglutinin (HA) subclade D.3.1 combined with either NA subclade D.1 or D.2 being most common. Based on shared sequence data, nearly all H275Y viruses from Australia, Canada, and Chile also belonged to these HA and NA subclades. Conversely, most H275Y viruses (68/81) from China belonged to HA subclade C.1.9 and NA subclade D and shared the permissive mutation R257K. Influenza polymerase acidic (PA) mutations conferring 4- to 92-fold decreased baloxavir susceptibility were detected in nine influenza A viruses. Viruses with PA-I38T showed mild attenuation of replicative fitness in three cell lines. Based on available data, NA-H275Y and PA-I38T viruses were collected from patients with no exposure to antivirals. Baseline susceptibility to all US-approved influenza antivirals remained largely unchanged compared to previous seasons. All swine-origin viruses detected in the US had adamantane resistance-conferring marker, M2-S31N, but remained susceptible to other approved antivirals. Monitoring antiviral susceptibility has substantially improved with increased sequencing capacities and bioinformatic support at public health laboratories. Information gained through influenza surveillance has been used to guide recommendations on antiviral use.

Source: 

Link: https://journals.asm.org/doi/10.1128/spectrum.01514-26

____

An imported case of #Bundibugyo virus #infection, #France, June 2026

 

Abstract

In June 2026, an intensive care physician deployed in the Democratic Republic of the Congo and previously vaccinated against Ebola virus developed fatigue, nausea and headaches while returning to France. Bundibugyo virus was identified with RT-PCR. The patient was treated with remdesivir and recovered fully. Contact tracing identified five low-risk contacts and no secondary cases. Stringent infection prevention and control measures and multidisciplinary collaboration are important when managing suspected or confirmed Ebola disease cases, even with low viral loads.

Source: 

Link: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2026.31.31.2600627?emailalert=true#abstract_content

____

The relationship between #plasma #favipiravir concentrations and #clinical #outcomes in #COVID19

 

Abstract

Background

Favipiravir has shown efficacy against SARS-CoV-2 in patients <60 years old, but data linking plasma concentrations to clinical outcomes are limited. This study investigated whether favipiravir plasma concentrations influence clinical efficacy and outcomes in patients hospitalised with COVID-19. The main research question was, How can antiviral dosing strategies be optimised to improve pandemic preparedness and treatment efficacy?

Methods

Adult participants were drawn from the PIONEER trial, in which patients received oral favipiravir (1800 mg twice daily for 1 day, then 800 mg twice daily for 9 days) plus standard care. This analysis included patients with confirmed COVID-19 and ≥75% study adherence. Samples were collected between days 5 and 10 post-treatment initiation. The primary outcome was time to clinical improvement. Secondary outcomes included achievement of clinical improvement and mortality risk.

Results

Out of 140 patients (50% male; mean±sd age 59.5±14.8 years), target plasma concentrations were reached in 29 (21%). Mean time to improvement was 7.7±5.9 days in target achievers versus 9.1±7.2 days in non-achievers (p=0.26). The target was more often achieved in female (34%) than male (7%) participants (p=0.0002). Plasma concentration inversely correlated with body mass index (r= –0.4, p<0.0001), and with lower body mass index in achievers (26.0±5.1 kg·m−2 versus 30.5±6.9 kg·m−2, p=0.003). Alkaline phosphatase and alanine aminotransferase levels were also lower in achievers (p=0.004 and p=0.02, respectively).

Conclusion

Most patients did not reach target favipiravir levels. Concentrations were influenced by sex, body mass index and liver function, confirming the need for pharmacokinetically guided dosing and therapeutic monitoring to optimise antiviral efficacy in future pandemic responses.

Shareable abstract @ERSpublications

Plasma favipiravir concentrations vary with sex, BMI and liver function. Concentrations in most patients fail to reach therapeutic levels, highlighting the need for personalised, pharmacokinetically guided dosing to optimise antiviral efficacy in future pandemics. https://bit.ly/4a6PvEa

Source: 

Link: https://publications.ersnet.org/content/erjor/12/4/01560-2025

____

Synergistic #antiviral effect of #Asunaprevir and #Ribavirin in combination against Murray Valley #Encephalitis Virus replication

 

Highlights

    • Renilla luciferase-based MVEV sub-genomic replicon was constructed and applied in antiviral drug evaluation.

    • Removal of Stem Loop I from 3’UTR impairs viral genome replication.

    • Asunaprevir and ribavirin exhibit synergistic antiviral activity against MVEV.

    • A single-round MVEV infectious particle platform was developed.

Abstract

Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus known for causing severe neurological diseases in humans. Despite the rising number of reported infections and high mortality rate among hospitalized patients, no antiviral therapies or licensed vaccines are available. To strengthen preparedness against this reemerging virus, we establish a subgenomic replicon (SGR) platform and a complementary single-round infectious particles (SRIPs) production system, using widely circulating genotype 1 (G1) MVEV as backbone. Stem-loop I(SLI) from 3’UTR stands for the major difference among 4 MVEV genotypes and removal of SLI resulted in mild decrease of genome replication. Through screening a mini anti-flavivirus drug library, we identified that asunaprevir (ASV) and ribavirin (RBV) inhibit MVEV infection independently. Combination of ASV and RBV also showed synergistic activity against MVEV. These results underscore the value of the MVEV replicon system as a versatile tool for evaluating antiviral compounds, supporting the potential of ASV and RBV as a combinatorial therapeutic approach.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0166354226001567?via%3Dihub

____

#Baloxavir, #favipiravir, or #oseltamivir in patients with non-severe symptomatic seasonal #influenza (AD ASTRA): a phase 2, open-label, adaptive, RCT

 

Summary

Background

The oral antiviral therapies baloxavir marboxil (hereafter baloxavir), favipiravir, and oseltamivir have not been simultaneously compared for the treatment of seasonal influenza. We aimed to determine their relative efficacies in accelerating viral clearance in patients with symptomatic influenza virus infection at low risk of progression to severe disease.

Methods

We conducted a phase 2, open-label, randomised, controlled, adaptive platform trial in patients aged 18–60 years in Thailand, Laos, Nepal, and Brazil, recruited in four hospital outpatient or primary care departments with acute influenza (≤ 4 days of symptoms) and a low risk of progression to severe disease. Patients were randomly assigned 1:1:1:1:1 using a centralised online app to receive baloxavir (single oral dose of 40 mg if bodyweight <80 kg or 80 mg if bodyweight ≥80 kg), favipiravir (oral loading dose of 1800 mg, followed by 1800 mg 12 h later, and then 800 mg twice daily for 4 days), oseltamivir (oral dose 75 mg twice daily for 5 days), no study drug, or another ongoing intervention (reported separately). Randomisation was stratified by site and used block sizes of 15. The primary endpoint was the rate of oropharyngeal influenza viral RNA clearance, estimated under a Bayesian hierarchical linear model fitted to the daily log10 oropharyngeal viral densities from day 0 to day 5. Analyses were conducted in the modified intention-to-treat population (mITT), defined as patients with PCR-confirmed influenza with more than 250 viral RNA copies per mL at randomisation. Intervention groups were assessed for superiority over the no study drug group (posterior probability >0·9 that the relative increase in viral clearance was ≥20%); if superiority was met, intervention groups were assessed for non-inferiority relative to baloxavir (posterior probability >0·9 that the relative reduction in viral clearance was ≤10%). Secondary outcomes included time to resolution of fever and time to resolution of all symptoms. The trial is registered with ClinicalTrials.gov (NCT05648448) and is ongoing.

Findings

Between Feb 22, 2023, and Dec 12, 2025, 944 patients with influenza virus infection were randomly assigned to baloxavir (n=199; mITT 163 [82%]), favipiravir (n=223; mITT 196 [88%]), oseltamivir (n=200; mITT 170 [85%]), no study drug (n=228; mITT 200 [88%]) or other interventions (n=94). 120 patients were excluded based on baseline viral density (≤250 copies per mL), and one participant withdrew before collection of quantitative PCR results on day 0. 457 (63%) patients in the mITT population were female and 272 (37%) were male. Compared with no study drug, viral clearance rates were accelerated by 86% (95% credible interval [CrI] 60–117) with baloxavir, 66% (45–94) with favipiravir, and 49% (28–74) with oseltamivir. For all interventions, the posterior probability that the relative increase in viral clearance was 20% or more was 1·0. Compared with baloxavir, oseltamivir was inferior (20% slower clearance, 95% CrI 6 to 32; posterior probability 0·93 that the relative reduction in viral clearance was <10%); non-inferiority could not be shown for favipiravir (10% slower clearance, 95% CrI –4 to 22; posterior probability 0·55 that the relative reduction in viral clearance was <10%). Median time to fever resolution was accelerated with all three antivirals compared with no study drug (absolute differences ranging from 0·5 days to 0·9 days), whereas time to resolution of all symptoms was not significantly different between groups. 31 adverse events of grade 3 or above occurred, five of which were considered severe (one in the favipiravir group, one in the oseltamivir group, and three in the no study drug group).

Interpretation

Oral baloxavir, favipiravir, and oseltamivir accelerated influenza viral clearance rates in adults with early non-severe seasonal influenza at low risk of progression to severe disease. Baloxavir had the greatest in-vivo antiviral efficacy, followed by favipiravir and oseltamivir. These antivirals shortened fever duration but showed no clear effects on time to complete symptom resolution. This pharmacometric approach can inform prioritisation of antiviral agents for further study and potential inclusion in pandemic stockpiles.

Funding

Wellcome Trust.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00255-0/fulltext

____

#Mutations in severe #human #H5N1 cases facilitate #evasion from human mucus and #antivirals

 

Abstract

In late 2024, two individuals in Canada and the United States were treated in intensive care for acute respiratory distress caused by infection with the avian Influenza A Virus H5N1 2.3.4.4b genotype D1.1. Viral sequence data obtained from sampling these patients indicated mixed alleles at haemagglutinin (HA) positions 190 and 226. Mutations at these positions are key determinants of HA usage of α2,6-linked sialic acids (SA), the most abundant influenza receptors in human upper respiratory tracts. Thus, these mutations raised concerns about human adaptation and pandemic potential of the H5N1 virus. In this study, we investigated the impact of the mutations at residues 190 and 226 in H5 HA. We studied the receptor binding properties, cell entry phenotypes and fitness impacts of the mutations using recombinant proteins, pseudotyped lentiviruses, and in the context of influenza viruses using reverse genetics. The mutations did not confer any detectable α2,6-linked sialic acid receptor usage either alone or in combination. Rather, viruses carrying these mutations exhibit weakened binding towards α2,3-linked sialic acid receptors. This correlated with an enhanced capacity to evade human airway mucus, and a reduced susceptibility to oseltamivir and zanamivir. This research underscores that in addition to the way HA interacts with SA as entry receptors, other factors that impact the HA/NA balance might influence the evolutionary trajectory of a zoonotic virus in the human respiratory tract. This study presents a new paradigm for the evolutionary drivers of HA, where reduced sialic acid binding can serve as an advantage for escape from host barriers and antivirals.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Medical Research Council, https://ror.org/03x94j517, MR/Y03368X/1, MR/Y015061/1, CC2127

Biotechnology and Biological Sciences Research Council, BB/Y007298/1, APP104179, BBS/E/PI/23NB000, BBS/E/PI/23NB0003

Wellcome Trust, https://ror.org/029chgv08, CC2127, 218304/Z/19/Z

Department for Environment Food and Rural Affairs, BB/Y007298/1

The Pirbright Institute, BBS/E/PI/230002A, BBS/E/PI/230001C, BBS/E/PI/230002B

Cancer Research UK, CC2127

UK Research and Innovation, https://ror.org/001aqnf71, UKRI3602

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.28.740943v1

____