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

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Predicting the #Risk of Avian #Influenza #Zoonosis using Viral #Genome Sequencing Data

 

Abstract

Avian Influenza viruses (AIVs) infect a broad host range despite having a natural reservoir in wild aquatic birds. Whilst most strains stay within their host species, some break the species barrier through genetic adaptations. We are most concerned about zoonotic cases, where a human becomes infected. Despite these events being rare, they are associated with high mortality and introduce the risk of onward human-to-human transmission of AIV. As a novel pathogen within the human population, this could have pandemic potential. Using genetic composition features for 8 AIV proteins drawn from viral sequence data, we employ machine-learning algorithms to classify AIV cases as zoonotic or not. These genetic features encode host 'signatures' which can indicate zoonosis and include frequency measures such as dipeptide composition and amino acid physiochemical properties. We consistently find XGBoost to outperform all other algorithms. We optimise parameters for ten classification models: one for each of the 8 proteins and two combined models. Following this, we show that a multi-model approach gives the best performing prediction for AIV zoonosis. We have identified all 8 proteins as having a role in predicting zoonotic transmission. Of particular importance is the PB2 and HA proteins, with specific amino acid physiochemical properties such as charge, secondary structure and hydrophobicity amongst the most indicative features in our combined models. Our alignment-free computational study can identify AIV cases still within avian hosts which are genetically closest to zoonotic AIV cases, thereby identifying the cases most likely to cross the species barrier. In a resource limited environment, our model could be used to quickly identify high priority cases for further investigation.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.21.746166v1

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Impaired #Neuraminidase and Polymerase Activities Correspond With Limited Aerosol Infectivity of #B3.13 and #D1.1 #H5N1 Lineages in #Human Respiratory Cultures

 

Abstract

The ongoing panzootic of clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 viruses has reached a critical point, marked by unprecedented mammalian spillover and sustained outbreaks in U.S. dairy cattle. While these viruses remain highly lethal in traditional ferret models, human infections-primarily linked to the B3.13 and D1.1 lineages-have been notably mild, typically presenting as conjunctivitis with minimal respiratory involvement. In this study, we address this disconnect by evaluating the infectivity of recent H5N1 isolates using a physiologically relevant air-liquid interface (ALI) culture system that incorporates an aerosol settling chamber. We demonstrate that while direct liquid inoculation leads to efficient replication, aerosolized H5N1 strains exhibit a significant defect in their ability to infect human respiratory epithelium. In contrast, a prototypic H5N1 virus remains highly pathogenic and lethal in ferrets regardless of the inoculation route, showing systemic dissemination to the brain and other organs. Our findings identify two primary viral determinants driving this respiratory restriction: reduced neuraminidase (NA) enzymatic activity and impaired polymerase activity. Collectively, these results suggest that commonly used mammalian models may overstate current human pandemic risk. This work highlights the critical need for alternative risk-assessment platforms to identify the specific genetic shifts required for these viruses to overcome existing barriers to human adaptation.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.18.745466v1

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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

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Characterisation of a #human monoclonal #antibody targeting a conserved epitope at the base of the HA head of #influenza #H3N2 virus

 

Summary

Background

Numerous broadly reactive human monoclonal antibodies (mAbs) against the haemagglutinin (HA) of influenza A viruses have recognised conserved epitopes across HA subtypes or within subtypes. Most heterosubtypic mAbs target the HA stem, the receptor-binding site (RBS), or the trimeric interface. Although at least three H3-specific mAbs recognise epitopes outside these regions, the overall landscape of conserved H3-specific epitopes remains incompletely understood. This study aimed to identify and characterise conserved epitopes on H3-HA to inform the development of vaccines resilient to antigenic change.

Methods

We screened a panel of previously reported H3-HA-reactive human mAbs to identify mAbs recognising conserved epitopes. The candidate clone, 034-10040 4F02 (4F02), was evaluated for neutralising, haemagglutination inhibiting, and HA-mediated fusion-inhibitory, Fc receptor-mediated effector functions in vitro, and for protective efficacy in a lethal mouse challenge model. Cryo-electron microscopy was used to define the structural basis of 4F02 binding. Human sera were screened for antibodies targeting similar epitopes.

Findings

Clone 4F02 recognised the HA of human influenza A (H3N2) viruses that circulated across multiple decades. It neutralised multiple H3N2 viruses, exhibited weak haemagglutination inhibition, blocked HA-mediated fusion activity, activated Fc receptor-mediated signalling, and protected mice against lethal challenge. Cryo-electron microscopy revealed that 4F02 targets the base of the HA head at a head-stem interface spanning antigenic sites C, D, and E. Antibodies targeting similar epitopes were detected, albeit at a low level, in human sera.

Interpretation

Characterisation of the 4F02 epitope reveals a previously underappreciated site of vulnerability at the H3-HA head-stem interface. This finding expands our understanding of conserved epitopes and provides a target for the development of influenza vaccines resilient to antigenic change.

Funding

This work was supported by the Japan Agency for Medical Research and Development, JSPS KAKENHI, the National Institutes of Allergy and Infectious Diseases.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00334-8/fulltext

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Serum Escape Landscape of #SARS-CoV-2 #Omicron JN.1 and XEC RBD Under #COVID19 #Vaccine Breakthrough #Immunity in #China

 

Abstract

Population immune pressure from vaccination and prior infection continues to drive the evolution of SARS-CoV-2. Systematic characterization of RBD mutations under complex immune backgrounds is essential for understanding viral adaptation and evolutionary trajectories. Here, we applied a deep mutational scanning (DMS) to comprehensively map the neutralization escape landscape of the Omicron variant JN.1 and its descendant lineage XEC, under immune pressure from individuals who experienced Omicron breakthrough infections following three doses of inactivated vaccines. A neutralization escape map for the single amino acid substitutions in the RBD of JN.1 or XEC was generated, and the escape efficiency of each mutation was determined. The results show that RBD escape mutations are hierarchically organized: low-intensity signals are widespread, whereas high-intensity escape is confined to a few key sites. These escape mutations are not confined solely to the receptor-binding motif (RBM) but are broadly distributed across the entire RBD. Many escape sites could accommodate multiple amino acid substitutions. Integration of DMS data with genomic surveillance of circulating variants from 2024 to 2025 revealed significant overlap between experimentally identified escape sites and mutations observed in natural isolates. This overlap increased substantially in 2025, with site concordance rising from 27.17% and 26.81% to 45.09% and 47.10% for JN.1 and XEC, respectively. The natural prevalence of these escape mutations is further shaped by factors such as receptor-binding affinity, protein stability, and epistatic interactions. Overall, our findings suggest that SARS-CoV-2 antigenic evolution follows the pattern of multiple pathways within a constrained space, providing new insights into the adaptive mechanisms of Omicron-derived variants under hybrid immune pressure.

Source: 

Link: https://www.mdpi.com/2076-2607/14/9/1872

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Transcriptomic and proteomic signatures following #AS03-adjuvanted #Influenza #H7N9 #vaccine

 

Abstract

Introduction: 

Vaccines targeting avian influenza virus A/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood.

Methods: 

We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal influenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that.

Results: 

AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood.

Discussion: 

Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness.

Clinical Trial Registration: https://clinicaltrials.gov/study/NCT02921997?term=NCT02921997&viewType, idientifier NCT02921997.

Source: 

Link: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1786231/full

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A mouse #monoclonal #antibody against #H7N9 #influenza virus cross-react with #human #platelets

 

Highlights

    • H7N9–98 mAb specifically binds human platelets and targets a ~60 kDa platelet protein.

    • H7N9 virus induces ITP via molecular mimicry with platelet antigens.

    • H7N9 virus-related ITP correlates with disease severity.

Abstract

Objective

To investigate the association and potential mechanisms between H7N9 influenza virus infection or vaccination and immune thrombocytopenia (ITP), providing foundational data for the prevention and treatment of related ITP.

Methods

Using laboratory-prepared anti-H7N9 influenza virus monoclonal antibodies (mAbs) (H7N9-98 and H7N9-120) as research subjects, the interactions between these antibodies and human platelets were analyzed through Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) techniques.

Results

The mAb H7N9-98 exhibited specific binding to human platelets, showing positive results in both IHC and IF assays. Western blotting results demonstrated that this antibody could specifically recognize approximately 60 kDa human platelet proteins. The isotype control mAb H7N9-120 did not exhibit the aforementioned binding reactions, with all test results being negative.

Conclusion

These findings suggest that the specific antibodies induced by the H7N9 virus may mediate platelet damage through cross-reactivity with platelet autoantigens. This mechanism warrants further investigation to provide experimental evidence for the pathogenesis of secondary ITP associated with H7N9 infection.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1567134826001346?via%3Dihub

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Emerging Haemagglutinin #Mutations in #Bovine-origin #H5N1 Influenza Viruses from #Humans and #Cattle Retain Avian #Receptor Binding with Increased Stability

 

Abstract

The current H5N1 panzootic has seen an unprecedented host range expansion, including sustained circulation in US dairy cattle, detected in March 2024. By July 2026, infections had been reported on more than 1,150 dairy farms across 19 states. Although the outbreak initially centred in Texas, California has emerged as the principal focus of transmission and accounts for most human infections associated with exposure to infected dairy cattle. Continued transmission in cattle and repeated spillover into humans increase opportunities for acquisition of mammalian-adaptive mutations that could elevate zoonotic and pandemic risk. The haemagglutinin (HA) protein plays a central role in modulating virus receptor binding and airborne transmission. Here, we characterised the receptor-binding and stability phenotypes of HA mutations identified in viruses circulating in Californian dairy cattle. Receptor-binding specificity was assessed using bio-layer interferometry and pseudotype virus entry assays. All tested HA variants maintained a preference for avian-type α2,3-linked sialic acid receptors. We evaluated HA stability using fusion and thermostability assays. All mutants exhibited fusion pH values >5.5, outside the range associated with efficient airborne transmission in humans (pH 5.0-5.5). However, mutations D88G and S94N increased pH stability, with fusion pH values of 5.6 and 5.7, respectively, compared with 5.9 for wild-type HA. Viruses harbouring both mutations displayed increased thermostability. These findings demonstrate that cattle-origin H5N1 viruses retain avian-like receptor specificity despite acquiring mutations that modestly enhance HA stability. Evolution of H5N1 viruses in dairy cattle underscores the importance of genomic and phenotypic surveillance to identify mutations that may increase zoonotic risk.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Biotechnology and Biological Sciences Research Council, BB/X006166/1, BB/Y007298/1, BB/X006204/1 BB/Y007271/1, APP104179,, BBS/E/PI/230001B, BBS/E/PI/230001C, BBS/E/PI/230002B, BBS/E/PI/230002C), BBS/E/PI/23NB0004, BBS/E/PI/23NB0003, BB/S011269/1

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

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.18.745528v1

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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

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Trimester-dependent vertical #transmission of #H5N1 #influenza virus through #placental and mammary routes impairs offspring development

 

Abstract

Avian influenza H5N1 has pandemic potential and historically causes more severe disease in pregnant women than the general population. With increasing transmission of H5N1 detected among placental mammals, animal models are necessary for testing countermeasures, including during pregnancy. Pregnant outbred mice infected with a contemporary strain of bovine H5N1 during the second trimester equivalent causes in utero transmission, with infectious virus detected in the uterus, placenta, and fetus. Birth following third trimester infection results in offspring with decreased size, neurodevelopmental delays, and adolescent behavioral impairments, with infectious virus detected in the neonatal milk ring and lungs, as well as mammary tissues. H5N1 viral protein colocalizes with trophoblast cells in the placenta and epithelial cells in mammary tissue that spatially overlap with lectins for α2,3-linked SA. With the pandemic potential of H5N1, our vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.

Source: 

Link: https://www.nature.com/articles/s41467-026-76891-9

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#Nipah virus #Malaysia and #Bangladesh strain-induced #pathogenesis in mice lacking type I #interferon receptor signaling

 

Abstract

Nipah virus (NiV) is a zoonotic highly pathogenic Paramyxovirus inducing lethal outbreaks of encephalitis and Acute Respiratory Distress Syndrome (ARDS) with an average case-fatality rate of 75%. Two viral strains, NiV-Malaysia (NiV-Mal) and NiV-Bangladesh (NiV-Ban), associated to distinct route of transmission, symptoms and lethality have been described. Due to the permanent threat of these emerging infections and the lack of approved therapeutics, it is crucial to improve our understanding regarding NiV-associated pathogenesis. Mice represent a small and accessible animal model, provided with numerous biological tools for the functional assessment of different genes related to antiviral response. Here, we explore the susceptibility of mice deficient for type I interferon receptor (IFNAR KO) to inoculation with either NiV-Mal or NiV-Ban through intraperitoneal or intranasal routes. Our results complement observations showing that IFNAR KO mice are susceptible to NiV-Ban infection via intraperitoneal route, although to a lesser extent than NiV-Mal, and develop encephalitis and a pulmonary syndrome with viral dissemination to various organs. Additionally, intranasal administration of both viral strains exhibited a subclinical infection with viral replication in the brain and the lungs along to the production of neutralizing antibodies in some animals. These results suggest that IFNAR KO mice may represent a reliable model permitting comparative studies of the immunopathogenesis induced by both NiV-Mal and NiV-Ban infections.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013894

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Detection of a novel #Shamonda #Orthobunyavirus in dairy #cattle, #France, June 2026

 

Abstract

In June 2026, acute fever, diarrhoea, lethargy and marked reduction of milk yield were reported in dairy cattle in eastern France. Unbiased Nanopore metagenomics on pooled plasma from affected cows detected Simbu serogroup Orthobunyavirus, provisionally named European Shamonda Virus, and recovered complete genomes. Segments L and M clustered with Nigerian Shamonda virus, whereas S showed a distinct clustering pattern, suggesting high mutation rate or reassortment. Similar findings in neighbouring countries indicate cross-border emergence requiring coordinated surveillance.

Source: 

Link: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2026.31.33.2600689?emailalert=true#abstract_content

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Cardiopulmonary Failure in #Hantavirus Disease: Mechanisms, Recognition, and #ECMO-Based Management

 

Abstract

Background: 

Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with case fatality rates of 25% to 40%. A 2026 outbreak aboard an expedition cruise ship in the South Atlantic, comprising 13 cases and three deaths, confirmed that Andes virus can be transmitted between humans in a confined setting remote from the rodent reservoir. 

Methods: 

Virological, pathophysiological, clinical, and therapeutic aspects of HPS were reviewed, with particular emphasis on cardiopulmonary mechanisms. Sources were identified through PubMed, Scopus, and Google Scholar, with priority given to original research articles, clinical series, and controlled trials published through 2025. Literature published in English and Spanish was included. 

Results: 

Pathogenic hantaviruses enter endothelial cells and platelets via αvβ3 integrins, disrupting the VEGF-VEGFR2 signaling axis and rendering endothelial cells hypersensitive to physiological VEGF concentrations. Expansion of CD8+ T cells and activated macrophages releases TNF-alpha, IFN-gamma, and nitric oxide, amplifying microvascular permeability and contributing to myocardial depression. Autopsy studies demonstrate direct hantaviral myocarditis with viral antigen in cardiac endothelium and interstitial macrophages. Transpulmonary thermodilution confirms simultaneous hypovolemia, reduced global ejection fraction, and elevated extravascular lung water. Because the incubation period is long and the cardiopulmonary phase is substantially immune-mediated, seroconversion precedes rather than follows clinical deterioration, which preserves the diagnostic utility of IgM serology in a disease that can kill within 48 h. VA-ECMO initiated at the first signs of cardiopulmonary decompensation has reported survival rates approaching 80% in selected experienced centers. No antiviral has demonstrated efficacy in controlled trials during the cardiopulmonary phase, and no licensed vaccine exists. 

Conclusions: 

HPS produces a mixed shock state through increased microvascular permeability, T cell-mediated immunopathology, and direct myocarditis. Management follows a stepwise algorithm: suspected HPS triggers immediate complete blood count with peripheral blood smear and concurrent hantavirus IgM serology and RT-PCR, followed by ICU admission, conservative fluid resuscitation guided by transpulmonary thermodilution, and early contact with an ECMO-capable center at the first sign of rising lactate, falling cardiac index, refractory shock, arrhythmia, or rapid oxygenation failure.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/915

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#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

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Conserved #influenza A #epitope candidate regions and a benchmark of ESM-2 #sequence features

 

Abstract

Influenza A virus antigenic drift forces annual vaccine reformulation, motivating the search for conserved epitope candidates that could support broadly protective vaccines. We systematically screened influenza A virus sequences (H1N1, H3N2, H5N1; nine viral proteins) to define 98 conserved candidate regions, 38 of which were identical across the H1N1, H3N2, and H5N1 consensus sequences, all in the polymerase complex and nucleoprotein (PB2, PB1, PA, NP), whereas the ten surface-glycoprotein (HA/NA) candidates were subtype-specific. We then benchmarked two protein-language-model (ESM-2) features against alignment conservation. Group-masked log-probability correlated moderately with MSA conservation (Spearman rho = 0.25 to 0.39 for HA) but provided no incremental value for T-cell epitope discrimination (change in AUROC +0.004, p = 0.46); attention-derived contact-density was not a valid solvent-accessibility proxy. A curated antibody-epitope benchmark (22 clusters, 5 neutralization-supported) was underpowered for a high-confidence B-cell test. We document data-quality and reproducibility pitfalls (length heterogeneity, coordinate mapping, and pseudoreplication) and release the auditable benchmark. These results provide an auditable candidate resource and show that, in the evaluated benchmarks, ESM-2 sequence scores did not improve epitope prioritization beyond alignment-derived conservation.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.16.745106v1

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Of Mice and Men: #Updates on #Hantavirus Disease and #Diagnostics

 

Abstract

Hantaviruses are a diverse and widespread group of zoonotic viruses under the Orthohantavirus genus that can cause severe acute cardiopulmonary or renal disease. Hantavirus species are grouped generally as either New World or Old World based on geographic distribution, which is influenced by their respective host reservoir including rodents. Although there is no specific treatment for hantaviruses, recognizing clinical presentation and interpreting laboratory results for case identification can improve patient management. Here we review the epidemiology, clinical manifestations, and diagnostic testing options for hantavirus infection.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S1386653226000843?dgcid=rss_sd_all

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#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

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