#Nirmatrelvir for acute #COVID19 to prevent #longCOVID (PANORAMIC Norway): a double-blind, randomised, placebo-controlled trial

 

Summary

Background

Long-term symptoms are common after acute COVID-19, particularly fatigue, cognitive problems, and dyspnoea. Cohort studies have suggested that antiviral treatment of acute COVID-19 might prevent development of post-COVID-19 condition (also known as long COVID), but the efficacy of antivirals has yet to be verified in prospective studies. We aimed to investigate whether treatment of acute SARS-CoV-2 infection with nirmatrelvir–ritonavir would reduce the risk of long COVID.

Methods

In this double-blind, randomised, placebo-controlled trial, participants were recruited from the municipal health-care service at three sites in Norway (Bergen, Oslo, and Ålesund). Non-hospitalised adults aged 18–65 years with SARS-CoV-2 infection confirmed by PCR or lateral flow test and symptoms for 5 days or fewer were eligible for inclusion. Key exclusion criteria included pregnancy or lactation, chronic renal impairment or chronic liver dysfunction, and any person judged by the investigator to need nirmatrelvir–ritonavir treatment due to increased risk of hospitalisation or death. Participants were allocated in a 1:1 ratio to receive oral 300 mg nirmatrelvir and 100 mg ritonavir, or placebo, twice a day for 5 days using a pre-generated randomisation list without stratification or block adjustment. Participants, clinicians, and the study team were masked to treatment allocation. The primary outcome was long COVID, defined as patient-reported fatigue, dyspnoea, and/or cognitive symptoms at 3 months’ follow-up. Safety was analysed as a secondary outcome, and included adverse events, hospital admissions, and deaths. Both the primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov (NCT05852873) and is now closed to new participants.

Findings

Between May 12, 2023, and June 11, 2025, we enrolled 144 participants, of whom 66 were assigned to nirmatrelvir–ritonavir and 78 to placebo. In the protocol we planned to enrol 2000 participants, but the trial was stopped prematurely by the steering committee due to insufficient recruitment. Among the 143 participants who completed follow-up, the risk of long COVID at 3 months was significantly reduced in the nirmatrelvir–ritonavir group (17 [26%] of 66) compared with the placebo group (33 [43%] of 77), corresponding to a relative risk after imputation of data for the single missing value in the placebo group of 0·60 (95% CI 0·37–0·98; p=0·039). In the nirmatrelvir–ritonavir group, five patients discontinued treatment due to adverse events. The most common adverse events in the nirmatrelvir–ritonavir group were change in taste or smell (57 [86%] of 66 in the nirmatrelvir–ritonavir group vs 14 [18%] of 78 in the placebo group) and nausea or vomiting (19 [29%] vs eight [10%]). Inversely, palpitations were more common in the placebo group (ten [13%] of 78) than in the nirmatrelvir-ritonavir group (two [3%] of 66). No severe adverse events were reported.

Interpretation

Treatment with nirmatrelvir–ritonavir for acute COVID-19 was associated with a significant reduction in the risk of long COVID at 3 months’ follow-up. The limited sample size precludes firm conclusions, and further clinical trials are warranted.

Funding

National Health Authorities’ KlinBeForsk programme, Western Norway Regional Health Authority, Helse Møre og Romsdal Hospital Trust, and The Influenza Centre, Haukeland University Hospital and University of Bergen, Bergen, Norway.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00244-6/fulltext?rss=yes

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#Safety and efficacy of #mRNA #vaccines: a mechanistic and public health perspective

 

Summary

mRNA vaccines represent a transformative advance in vaccinology, combining rapid development timelines, scalable manufacturing, and strong immunogenicity with a favourable safety profile. Global deployment of mRNA vaccines during the COVID-19 pandemic provided an unprecedented real-world evaluation of this platform, with billions of doses administered across diverse populations. In this Review, we critically examine the safety and efficacy of mRNA vaccines from mechanistic, preclinical, clinical, and public health perspectives. We outline the biological basis of mRNA vaccines, including their transient cytoplasmic expression, lack of genomic integration, and rapid clearance, distinguishing them clearly from other gene therapies. We synthesise evidence on vaccine components, manufacturing quality controls, and regulatory standards that underpin safety, alongside data from randomised trials, post-authorisation surveillance, and active pharmacovigilance systems. We also review real-world effectiveness across age groups, pregnancy, and populations that are immunocompromised, along with the effects on transmission. Last, we address public perception and vaccine confidence, and discuss implications for next-generation mRNA vaccines, including strategies to reduce reactogenicity, improve breadth and durability of immunity, enhance global access, and support sustainable public trust. Together, the accumulated evidence affirms mRNA vaccines as a safe, effective, and adaptable platform with enduring relevance for future infectious disease prevention and public health preparedness, and for the treatment of cancer and autoimmunity.

Source: 

Link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00512-X/abstract?rss=yes

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#Autoantibodies against type I #interferons in patients with #zoonotic #H7N9 #influenza: an observational case–control study

 

Summary

Background

The determinants of the species barrier preventing human infections with avian influenza A viruses (IAV) are incompletely understood. We previously identified loss-of-function variants of the interferon-regulated antiviral factor MxA as a genetic factor for increased susceptibility to infections with the H7N9 subtype. Given the central role of type I IFNs (IFN-I) in antiviral defence, we hypothesised that IFN-I-neutralising autoantibodies may similarly predispose to zoonotic H7N9 infection.

Methods

In this observational case–control study, serum samples collected between 2013 and 2017 from 199 Chinese patients with laboratory-confirmed H7N9 infection and 531 healthy, uninfected controls (269 poultry workers, 262 close contacts) were screened for IgG autoantibodies binding IFNα2, IFNβ1b, or IFNω using a multiplex bead-based assay. Positive samples were tested for IFN-neutralising activity in a luciferase-based reporter assay. To confirm their ability to block IFNα2-mediated antiviral activity, selected samples (n = 19) were analysed in IAV infection experiments. Associations between age, sex, H7N9 case status, case fatality, and the presence of neutralising autoantibodies were evaluated by logistic regression. Available whole-genome sequencing data from 26 individuals with neutralising autoantibodies were screened for variants in genes linked to IFN-I autoimmunity.

Findings

Neutralising autoantibodies against at least one IFN-I were detected in 19.1% (38/199) of patients but in only 1.1% (6/531) of controls, consistent with published general population data. Most patient sera targeted IFNα2 and/or IFNω (35/199), and 18.1% (36/199) neutralised even high IFN-I concentrations of 1–10 ng/ml. The presence of neutralising autoantibodies was associated with 8.2- to 25.3-fold higher odds of H7N9 infection (p < 0.0001), depending on antibody specificity and reference group. Autoantibody prevalence increased significantly with age in patients (44.8% ≥70 years; OR = 1.05; 95% CI 1.02–1.07; p = 0.0001), but was not associated with sex (OR for males vs. females = 0.52; 95% CI 0.23–1.14; p = 0.106). All selected sera containing neutralising autoantibodies blocked IFNα2-induced antiviral activity in cell culture. No known genetic predisposition for IFN-I autoimmunity was identified.

Interpretation

Our findings suggest that IFN-I-targeting autoimmunity is associated with susceptibility to zoonotic IAV infection with the H7N9 subtype, and possibly also other subtypes, including panzootic H5N1. Given the ease of implementation, screening for anti-IFN-I autoantibodies could be readily integrated into surveillance or targeted testing. This could be relevant in environments with increased exposure to zoonotic IAVs.

Funding

Shenzhen Medical Research Fund, National Natural Science Foundation of China, Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, Guangdong Provincial Science and Technology Program, Program for Youzuzhikeyan of Shenzhen University, German Research Foundation, Swiss National Science Foundation.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00271-9/fulltext

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#Hantavirus cardiopulmonary syndrome in #children: a systematic scoping #review of presentation, critical care management, and outcomes

 

Abstract

Background

Pediatric hantavirus cardiopulmonary syndrome/hantavirus pulmonary syndrome (HCPS/HPS) is rare but can progress rapidly from a nonspecific febrile prodrome to respiratory failure, shock, and multiorgan dysfunction. Pediatric-specific evidence is limited, and a comprehensive map of the clinical literature is lacking.

Methods

We conducted a systematic scoping review per Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidance (protocol registered at DOI:10.17605/OSF.IO/MZDN4). PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL were searched from inception to May 2026. Eligible reports described children or adolescents (age ≤18 years) with HCPS/HPS and extractable pediatric clinical data. Two reviewers independently screened records, assessed overlap, extracted data, and appraised reporting quality using Joanna Briggs Institute tools.

Results

Of 2208 database records, 20 reports were included in the core pediatric synthesis after removal of 976 duplicates and screening. Reports were concentrated in the Americas. Recurrent features included fever, gastrointestinal symptoms, myalgia, thrombocytopenia, hemoconcentration, pulmonary edema, respiratory failure, and shock. Severe cases required mechanical ventilation, vasoactive support, extracorporeal membrane oxygenation, and in some cases renal replacement therapy. Larger pediatric case series and surveillance-level reports reported mortality of approximately 33% to 37%. Evidence was predominantly case-based with variable reporting completeness.

Conclusions

Pediatric HCPS/HPS is rare but potentially rapidly fatal. Early suspicion in endemic regions or after rodent exposure, with prompt supportive critical care and timely consideration of advanced cardiopulmonary support, is central to management.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/08998280.2026.2698359

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#Ribavirin post-exposure #prophylaxis for #Andes virus #exposure: a viewpoint

 

Summary

Andes virus (ANDV) is unique among hantaviruses because person-to-person transmission is possible. This raises questions on the relevance of post-exposure prophylaxis (PEP), particularly following high-risk household, healthcare-associated, or laboratory exposures, considering its high case fatality rate. Ribavirin has demonstrated antiviral activity against hantaviruses in vitro and in animal models, although clinical evidence supporting its use for ANDV remains extremely limited. This viewpoint summarises the currently available evidence regarding ribavirin as PEP after potential ANDV exposure. We discuss the knowledge gaps that may limit the applicability of ribavirin PEP, to make informed decisions on the use of ribavirin in the setting of PEP. Potential dosing strategies are visualised by modelling and simulation, and potential dose and duration are discussed. Although the biological rationale for ribavirin PEP appears compelling, absence of controlled human studies and potential toxicity currently limit its role to highly selected exposure scenarios and use shortly after exposure.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00270-7/fulltext

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Pan-continental #spillover #risk: integrated spatiotemporal, transmissibility and #surveillance analysis of avian #influenza #H5N1 in #Africa

 

Abstract

Background: 

The HPAI H5N1 panzootic represents a critical threat to human health in Africa, where traditional poultry systems and dense human-animal interfaces facilitate frequent zoonotic spillover. While sporadic human cases raise pandemic concerns, continent-wide integration of spatial dynamics, transmissibility indicators, and surveillance performance has been lacking. This study quantifies avian influenza transmission over two decades across Africa, identifies geographical hotspots, and evaluates the responsiveness of current surveillance systems.

Methods: 

We analysed 8,037 avian influenza outbreak events and 369 laboratory-confirmed human cases, predominantly caused by HPAI H5N1 (2004–2025), using harmonised data from FAO (EMPRES-i+), WHO, and WOAH. A Bayesian Besag-York-Mollié (BYM) spatiotemporal model estimated residual transmission risks and Incidence Rate Ratios (IRR) by subtype. The basic reproduction number (R₀) was derived via an exponential growth model applied to human outbreak phases across infectious durations of 7–30 days. Surveillance responsiveness was assessed by quantifying notification delays between clinical observation and official reporting.

Results: 

Risk of infection in animals: HPAI H5N1 was the dominant strain, representing 87.8% of animal cases, with Egypt acting as the primary epidemiological epicentre (66% of total records). The spatiotemporal model revealed that H5N1 is associated with a significantly higher risk of animal infection (IRR = 8.37; 95% CI: 6.65–10.53). Although 71% of outbreaks were reported within 5 days of detection, significant delays (≥15 days) occurred in 12% of cases, with notable regional disparities. Risk of infection in human: H5N1 was associated with a 67-fold increase in the incidence of human cases compared to other subtypes (IRR = 66.78; 95% CI: 25.29–176.37). Sensitivity analyses yielded R0 estimates ranging from 1.05 (95% CI: 0.91–1.31) to 1.23 (95% CI: 0.60–2.33), indicating localised epidemic potential.

Conclusion: 

Our findings highlight a persistent and geographically heterogeneous H5N1 reservoir in Africa with high zoonotic affinity. Although sustained human-to-human transmission remains limited, the identification of dual poultry-human hotspots and localised R0 peaks underscores the urgent need for geographically targeted One Health interventions. Strengthening real-time reporting systems and improving biosecurity in high-risk poultry value chains are critical to mitigating future pandemic threats on the continent.

Source: 

Link: https://www.frontiersin.org/journals/epidemiology/articles/10.3389/fepid.2026.1813211/full

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#Camel #Prion Disease, Tataouine, #Tunisia, 2019–2021

 

Abstract

We report 6 cases of camel prion disease in dromedaries in Tunisia, confirming widespread occurrence in North Africa. Affected animals showed neurologic signs and scrape prion protein accumulation in brain and lymphoid tissues. These findings highlight the importance of active surveillance and investigation of the epidemiology, transmission, and public health implications.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1474_article

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Identification of #Contacts With High Rates of Missed and #Asymptomatic Infection Following an #Outbreak of #Ebola Virus Disease: A Seroepidemiological Study in Likati Health Zone, #DRC

 

Abstract

Background

Ebola virus disease (EVD) is often regarded as severe and highly fatal, but growing evidence suggests that subclinical or minimally symptomatic infections occur and frequently go undetected. During the 2017 outbreak in Likati Health Zone, only 8 cases were confirmed despite many reported exposures. We evaluated the extent of asymptomatic or unrecognized Ebola virus infection and associated factors among contacts of reported cases.

Methods

In November 2017, we conducted a cross-sectional community-based serosurvey among contacts originally identified through Ministry of Health records and newly identified through additional post-outbreak investigations. Participants provided blood samples and completed questionnaires on demographics, exposures, and symptoms within 4 weeks of symptom onset of the EVD case with whom contact was reported. Sera were tested for anti-EBOV nucleoprotein IgG by ELISA. Seropositive individuals were classified as asymptomatic (no symptoms) or unrecognized (≥1 symptom). Secondary attack rate (SAR) was estimated, and logistic regression assessed associations with sociodemographic factors, exposure level, and symptoms.

Results

Among 180 participants (79 originally identified; 101 newly identified), 33 (18.3%) were seropositive. Of these, 19 (58%) reported symptoms, and 14 (42%) were asymptomatic. Any EVD-related symptom was associated with higher odds of seropositivity (OR 2.48, P = .021), though no specific symptom was significant. Asymptomatic individuals had higher antibody titers than symptomatic seropositive contacts (P = .009). The overall SAR was 19.1% (95% CI: 15.9–23.0). High exposure level strongly predicted seropositivity (OR 11.2, 95% CI: 3.8–33.3).

Conclusions

Asymptomatic infections occurred, including among contacts missed during the response, highlighting the need for exposure-based serologic assessments in EVD investigations and raising questions about immune responses and the true disease burden in outbreak-affected settings.

Source: 

Link: https://academic.oup.com/ofid/article/13/7/ofag397/8725922

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#Screening and #monitoring of #travellers returning from countries affected by #Bundibugyo virus: an overview of #European approaches, July 2026

 

Abstract

The 2026 Ebola outbreak caused by Bundibugyo virus in the Democratic Republic of the Congo and Uganda has prompted European countries and the United States to revise measures for travellers, healthcare workers and humanitarian personnel returning from affected areas. We compare current procedures and protocols with those implemented during the 2013–2016 Ebola outbreak. Despite some national differences, policies have largely converged towards risk-based management, early case detection, rapid isolation, exposure-based monitoring and healthcare preparedness, rather than routine border screening.

Source: 

Link: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2026.31.28.2600578?emailalert=true#abstract_content

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Occupationally Exposed and General #Population #Antibody #Profiles to #Influenza A Viruses Circulating in #Swine as Indication of Zoonotic #Risk

 

Abstract

Persons with occupational exposure to swine might be at disproportionate risk for zoonotic swine influenza A virus. To evaluate human antibody responses, we tested serum or plasma from swine veterinarian, farm employee, and general population cohorts by hemagglutination inhibition assays against representative swine and human seasonal influenza vaccine strains. We analyzed hemagglutination inhibition data by antigenic cartography to assess strain relationships and reproduction number modeling to evaluate pandemic potential using age-stratified immunity profiles. Occupationally exposed groups had lower human seasonal vaccine uptake (45.5% vs. 70%) and lower odds of seropositivity to several H1 and H3 strains from swine than did general population cohorts. One swine strain exhibited significant antigenic drift (3.62 antigenic units) from its nearest vaccine strain. Multiple strains required lower reproduction number thresholds for pandemic spread (1.09–1.35) than recorded pandemic strains (1.46–1.80), demonstrating that population immunity gaps heighten zoonotic risk to circulating swine H1 and H3 strains.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1995_article

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First nationwide full- #genome characterisation of #human-derived #Andes virus in #Chile: a retrospective genomic #epidemiology study

Summary

Background

Andes virus (ANDV) is the only hantavirus known to transmit between humans and causes hantavirus cardiopulmonary syndrome in Chile and Argentina. In Chile, ANDV genomic diversity remains incompletely characterised. This study aimed to characterise the genetic diversity, geographical structure, and molecular signatures of ANDV using human clinical samples collected over a 13-year period (2011–24).

Methods

We conducted a retrospective genomic epidemiology study of ANDV infections in Chile. Clinical samples from patients with confirmed ANDV, collected between March 9, 2011, and June 27, 2024, were analysed and sequenced. Clinical and epidemiological data were obtained from diagnostic laboratories and surveillance programmes. Consensus sequences for the S, M, and L segments were generated, and genetic clustering and divergence were assessed using phylogenetic inference and variant calling.

Findings

We analysed clinical samples from 58 infected individuals and identified two major genomic variants of ANDV with distinct geographical distributions, defined by regionally structured patterns of nucleotide and amino acid substitutions across the S, M, and L segments: ANDV Chi-North (central Chile) and ANDV-South (southern Chile). No consistent clustering by clinical severity was observed, and no recurrent non-synonymous substitutions were uniquely associated with severe disease. Substitutions previously associated with person-to-person transmission in outbreaks in Argentina were not consistently observed in Chilean sequences, including in four person-to-person transmission cases. Although some substitutions described in ANDV-like viruses were present in the Chi-North lineage, this lineage remained phylogenetically distinct and geographically restricted to central Chile.

Interpretation

To our knowledge, this study provides the first nationwide genomic characterisation of human-derived ANDV in Chile. The identification of geographically structured variants indicates that ANDV diversity in Chile is driven by regional diversification rather than clinical outcome. The absence of consistent amino acid signatures associated with disease severity or person-to-person transmission suggests that these phenotypes are unlikely to be explained by viral genetic variation alone. These findings refine current understanding of ANDV evolution and highlight the need for continued integrated genomic surveillance in endemic regions.

Funding

Agencia Nacional de Investigación y Desarrollo de Chile and National Institutes of Health.

Source: 

Link: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(26)00109-6/fulltext

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#Bundibugyo #ebolavirus from the 2026 Ebola #outbreak in #Uganda and #DRC: a new #variant

 

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In conclusion, we show that the BDBV variant identified in Uganda from a travel-related case linked to the ongoing outbreak in Ituri represents a new clade of BDBV. These findings underscore the diversity of the BDBV ecosystem and the urgent need for antiviral and vaccine countermeasures to reduce fatalities and for public health measures to limit the spread of the virus. Global efforts are immediately needed in this region. Continued genomic surveillance is required for in-depth monitoring to track emerging BDBV variants and adjust and employ BDBV countermeasures in a timely manner.

Source: 

Link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01079-2/fulltext

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#Andes Virus — A #Clinical #Review

 

Summary

Andes virus (ANDV) is the sole orthohantavirus with documented human-to-human transmission. We summarize the epidemiology and clinical features of ANDV infection and review best practices in clinical management, as based on published expert consensus guidelines, field experience, and clinical trials. We also evaluate currently available and investigational treatments (including the use of antiviral agents), assess emerging monoclonal antibody therapies, and outline prospects for vaccine development. Finally, we discuss important infection prevention and control measures.

Source: 

Link: https://www.nejm.org/doi/full/10.1056/NEJMra2606651?query=TOC

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Detection of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype #D1.2 Virus in #Swine after Experimental Inoculation

 

Abstract

Highly pathogenic avian influenza H5NX clade 2.3.4.4b viruses continue to circulate globally. Reintroduction of Eurasian lineage viruses into North America and reassortment with endemic low pathogenicity strains have resulted in new genotypes, including D1.2. To assess pathogenicity and cellular tropism, we intranasally inoculated genotype D1.2 virus into pigs. We isolated virus from nasal secretions from most inoculated animals for multiple days. At 5 days postinoculation, PCR and immunohistochemistry detected virus in musculoskeletal, respiratory, digestive, lymphatic, and nervous systems and isolates from meat juice. At 35 days postinoculation, we detected viral antigen and low levels of RNA in the brain of an animal with lesions consistent with a viral etiology and found viral antigen in the ethmoid of 2 animals. Consistent detection in nasal swab specimens, combined with subclinical respiratory infection, systemic distribution, and protracted detection of clade 2.3.4.4b virus in swine, suggest identifying infection in commercial swine without overt respiratory signs could be difficult.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1765_article

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A systematic #review of #Nipah virus disease epidemiological #parameters, #outbreaks, and mathematical #models

 

Summary

Our systematic review, based on PRISMA guidelines (PROSPERO CRD42023393345), characterised the epidemiology, outbreaks, and mathematical models of Nipah virus, an important public health threat in south and southeast Asia. We searched PubMed and Web of Science from database inception to March 14, 2025, and extracted 243 parameters, 89 risk factors, 39 models, and 23 distinct outbreaks from 119 papers. IgG seroprevalence estimates in the general population ranged from 0% to 12·5%. Nipah virus causes severe disease, with pooled case–fatality ratio estimates ranging widely from 9·1% (95% CI 0·2–41·3) in Singapore to 81·9% (95% CI 71·9–88·9) in Bangladesh. The infection timeline and clinical course of Nipah virus remain poorly characterised; we estimated a median incubation period of 8·77 days (165, 95% CI 7·53–10·02) from eight estimates in seven articles with sufficient information. Transmission parameter estimates were scarce, and all but one of five central estimates of the basic reproduction number were less than one. Nipah virus mathematical models (39) were rarely fitted to data (eight). All extracted information is accessible via our R package, epireview.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00239-2/abstract?rss=yes

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#Neurological Manifestations of #Hantavirus Infection - A Review

 

Abstract

Importance  

Hantaviruses have caused several recent human disease outbreaks. They carry a high mortality rate, and some species can spread from person to person although they are typically spread from rodents to humans. Neurological complications have been documented but are poorly understood.

Observations

Broadly, 2 types of syndromes have been associated with hantaviruses. The pulmonary syndrome carries a high mortality rate and can result in pulmonary and cardiac failure. Neurological involvement is typically secondary to hypoxic and ischemic injury or metabolic dysfunction. Another manifestation of the infection that is associated with some species of the virus is termed hemorrhagic fever with renal syndrome. Some patients may develop a meningoencephalitis or pituitary apoplexy resulting in sudden visual loss and pituitary dysfunction. Rarely, seizures, myelitis, and peripheral neuropathy may occur. Although there are no specific antiviral drugs approved for treatment of hantavirus, there are several that showed efficacy in preclinical trials. Management is supportive care and treatment of symptoms.

Conclusions and Relevance  

Neurological manifestations of hantavirus infection are uncommon but can be severe. Prospective studies and experimental models are needed to better characterize these manifestations, understand pathophysiology, identify therapeutic targets, and develop guidelines for management.

Source: 

Link: https://jamanetwork.com/journals/jamaneurology/fullarticle/2851731

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Rapid #Expansion of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype #D1.1 Virus across #Flyway Regions, North #America, Fall 2024

 

Abstract

Highly pathogenic avian influenza clade 2.3.4.4b virus continues to circulate in North America and has caused severe human disease. That clade includes genotype D1.1, which became dominant in birds in late 2024. Recent phylodynamic reconstructions place D1.1 emergence in mid-2024 but differ on its inferred origin and early dissemination pathways. We combined targeted surveillance of wild birds in Arizona with publicly available US clade 2.3.4.4b hemagglutinin sequences to estimate when D1.1 genotype emerged and to infer its diffusion among the 4 major US flyways. Phylodynamic analyses showed transitions concentrated among adjacent flyways regions, consistent with stepwise dissemination during fall 2024 and limited support for long-distance Pacific–Atlantic exchange. The Pacific Flyway showed patterns consistent with an early source and the Central Flyway with a secondary hub linked to onward spread. Our findings support coordinated genomic surveillance across adjacent flyways to reduce detection delays and improve situational awareness during rapid viral expansion.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/26-0205_article

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Highly Pathogenic Avian #Influenza #H5N1 in South #America, 2022–2025: Spread, Affected Species, and Southward Expansion into the #Antarctic Region

 

Abstract

The H5N1 highly pathogenic avian influenza (HPAI) virus has caused severe global losses, reaching South America in 2022 and Antarctica in 2024. Here, we synthesize outbreak reports submitted to the World Organization for Animal Health by South American countries and overseas territories in this continent, and document the virus’s unprecedented expansion into Antarctica, affecting wild birds, wild mammals, and domestic poultry. Phylogenetic and time-calibrated Bayesian analyses were performed on available genomic sequences. Over 6 million domestic birds were lost, mostly from commercial operations. Of the 11 South American countries and overseas territories that reported H5N1 to WOAH, 10 reported infections in wild birds, spanning 104 species, 59.62% of which are migratory and predominantly non-trans-equatorial. Marine mammal outbreaks followed wild bird detections, with the South American sea lion (Otaria flavescens) being the most reported species. Several Antarctic bird species with migratory behavior were also reported in South America. Genomic analyses revealed multiple introduction events, regional viral diversification, and patterns consistent with repeated cross-species spillover events. These findings highlight H5N1’s extensive ecological reach in the Southern Hemisphere and underscore the urgent need for a One Health approach that strengthens wildlife and backyard-poultry surveillance, alongside coordinated regional action to control and prevent further HPAI spread.

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/764

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#MHC-II acts as a #fusion-triggering #receptor for #bat #influenza virus

 

Abstract

Influenza A virus hemagglutinin is a prototypical class I viral fusion protein that binds sialylated glycans and is activated by low pH in endosomes. In contrast, bat-derived IAV subtypes H17N10 and H18N11 use major histocompatibility complex class II (MHC-II) as an entry receptor, but how this receptor contributes to membrane fusion remains unknown. We find that MHC-II-dependent hemagglutinin subtypes H17, H18, and H19 possess an increased negative net charge relative to canonical HAs. Using cryo-electron tomography, we demonstrate that H18N11 morphology remains stable and H18 is in prefusion conformation at strongly acidic pH. Remarkably, H18 undergoes fusion-relevant conformational changes only when both MHC-II binding and low pH are present. By reconstitution of H18N11 fusion with liposomes and purified MHC-II, we show that receptor engagement is required to trigger the fusion activity of H18. These findings identify MHC-II as a receptor that directly triggers membrane fusion and reveal a previously unrecognized receptor-dependent mechanism of influenza virus entry.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, 240245660 – P19, 537227910

European Research Council, 882631—Bat Flu

Excellence Initiative of the German Research Foundation, GSC-4, Spemann Graduate School

Hans A. Krebs Medical Scientist Programme

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.08.737388v1

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Lactylation of #Influenza Virus #Polymerase Acidic Protein Promotes Viral #Replication and #Pathogenicity

 

Abstract

Influenza virus poses a potential risk of triggering the next global pandemic. In-depth investigation into the mechanisms underlying influenza virus replication and pathogenicity will provide robust support for controlling influenza virus infection. Although post-translational modifications are known to regulate viral infection, the role of lactylation in influenza virus replication remains elusive. In this study, influenza virus ribonucleoprotein complex subunits are found to be lactylated. Specifically, ATAT1 promotes viral polymerase acidic protein (PA) lactylation and enhances viral replication. In contrast, SIRT1 mediates de-lactylation of PA and exerts an inhibitory effect on viral replication. Further investigations reveal lactylation of PA at residues K605 and K609 is essential for viral replication and pathogenicity. Mechanistically, PA K605/609 residues are localized at the interaction interface of the ANP32-mediated polymerase asymmetric dimer; mutation at these residues inhibits polymerase asymmetric dimerization, thereby impairing RNA production during viral genome replication. Collectively, this study uncovers a novel mechanism by which influenza virus hijacks host enzymes to mediate PA lactylation, and expands the molecular regulatory network of influenza virus infection.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.10.737663v1

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