#Pathogenesis and natural history of the #Bundibugyo species of #Orthoebolavirus in nonhuman #primates

 

Abstract

The current outbreak of Bundibugyo virus (BDBV) in Africa is a global public health concern particularly as there are no licensed medical countermeasures (MCM). Well characterized animal models that accurately replicate human BDBV infection are needed to develop effective MCM. We exposed 21 cynomolgus monkeys (CM) to BDBV to examine the progression and natural history of BDBV disease (BVD). BVD was more protracted than reported for Ebola and Sudan infection in CM with a lower lethality rate of 67% consistent with lower human BVD mortality rates. IHC and spatial proteomics identified CD209+, CD68+, and/or HLA-DR+ macrophages and dendritic cells as early targets of BDBV. These infected cells frequently colocalized with fibrin and infiltrating MPO+ neutrophils and S100A9+ myeloid-derived suppressor cells, consistent with the development of an active inflammatory response and early coagulopathy. Transcriptomic and proteomic analyses of the circulating immune response correspondingly reflected a cytokine-driven hyperinflammatory state in CM that succumbed to disease. Surviving animals resolved systemic inflammation by the study endpoint; however, BDBV antigen was identified in immune privileged tissues with lesion-associated inflammation aligning with known post-Ebola sequela in humans. This data should assist in identifying weaknesses in the disease course that can be exploited to develop new MCM.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, https://ror.org/043z4tv69, U19AI109945

The University of Texas Medical Branch at Galveston, https://ror.org/016tfm930, N/A

Source: 

Link: https://doi.org/10.64898/2026.08.10.743937

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Assessment of immune #response induced by ChAdOx1 nCoV-19, Sputnik V, and BNT162b2 #vaccines during #COVID19 #outbreak in #Mexican population: Gene expression of the #cytokine storm

 

Highlights

    • The molecular immune response triggered by vaccines against COVID-19 was analyzed.

    • The evaluated genes were ACE2, CD79B, TMPRSS2, CTSB, FCGR3A and MB-1.

    • These vaccines induce a protective immune response through various mechanisms.

    • Vaccines regulate the immune response through pro- and anti-inflammatory cytokines.

Abstract

Introduction

COVID-19 vaccines using different technological platforms may induce distinct molecular responses. Characterizing gene-expression patterns after vaccination and in fatal COVID-19 may identify pathways associated with vaccination and severe disease.

Objective

To compare immune-, inflammatory-, and SARS-CoV-2-entry-related gene expression after AstraZeneca, Pfizer, or Sputnik V vaccination and with unvaccinated fatal COVID-19.

Materials and methods

Eighty Mexican adults were included: AstraZeneca (n = 19), Pfizer (n = 20), Sputnik (n = 21), and unvaccinated fatal COVID-19 (n = 20). Expression of 11 genes was measured by qPCR at days 30 (D30) and 60 (D60) after vaccination.

Statistical analysis

Longitudinal differences were analyzed by two-way repeated-measures ANOVA. Comparisons with fatal COVID-19 were exploratory. Benjamini–Hochberg correction controlled false discovery rate at 5%.

Results

No differences among vaccines were detected at D30. At D60, IL-10, IL-2, and CD79A differed among selected vaccine groups. Longitudinally, FCGR3A decreased in AstraZeneca and Sputnik, ACE2 decreased in Pfizer and Sputnik, and TMPRSS2 increased in Sputnik. Fatal COVID-19 showed predominantly higher expression of several genes than vaccinated groups. Notably, IL-2 and ACE2 were consistently higher in fatal COVID-19 than in all vaccinated groups at both time points.

Discussion and conclusions

Post-vaccination transcriptional profiles were dynamic, with selected differences emerging at D60, whereas fatal COVID-19 exhibited a distinct profile characterized predominantly by higher expression of immune-, inflammatory-, and viral-entry-related genes. Consistent IL-2 and ACE2 differences highlight molecular pathways potentially associated with severe disease. The observational design, however, precludes causal attribution to vaccination.

Perspectives

Longitudinal studies with appropriate controls are needed to establish the biological significance of these transcriptional patterns.

Source: 

Link: https://doi.org/10.1016/j.meegid.2026.106025

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Respiratory #pandemic #risk in the #Anthropocene: A #OneHealth #framework and #GISRS+ agenda

 

Highlights

    • Respiratory pandemics are now a structural feature of the Anthropocene.

    • H5Nx and SARS-related CoVs are identified as leading pandemic candidates.

    • A geographic mismatch exists between spillover risk and surveillance.

    • A multidimensional GISRS+ agenda is proposed for proactive One Health.

Abstract

Recent epidemics and pandemics caused by respiratory viruses, alongside the animal panzootic spread of highly pathogenic avian influenza A(H5Nx), have become a structural feature of the Anthropocene, yet responses remain largely reactive. This review integrates findings from WHO's Global Influenza Surveillance and Response System (GISRS) and related surveillance data (2000–2024), epidemiological studies of influenza A virus, SARS-CoV, MERS-CoV, SARS-CoV-2, and H5Nx, and One Health literature. We examine major groups of respiratory viruses and identify mismatches between risk and surveillance by focusing on spillover potential from animal hosts, human-to-human transmission and its controllability, and Anthropocene characteristics that increase epidemic risk. The analysis indicated that SARS-related coronaviruses and influenza A viruses, particularly H5Nx, are among the leading candidates based on currently available evidence because they have large reservoirs in animal hosts and spillover to humans is highly probable. The previous presymptomatic spread of SARS-CoV-2 and recent mammalian adaptation in H5N1 clade 2.3.4.4b highlight limitations of the traditional symptom-based and pathogen-specific surveillance system. Spillover events tend to occur in tropical and subtropical regions in low- and middle-income countries, but most genomic surveillance is in high-income countries. We propose interventions that address the upstream, midstream, downstream processes of epidemics. Upstream interventions are primary prevention measures related to land use, livestock, wildlife, and urban environments; midstream interventions are GISRS+-based pathogen-agnostic genomic and metagenomic early warning systems triggered by One Health; and downstream interventions include vaccines, antivirals, non-pharmaceutical interventions, and engineering with equity-centred global governance and sustainable financing.

Source: 

Link: https://doi.org/10.1016/j.onehlt.2026.101553

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Divergent #antibody-mediated population #immunity to #H5, #H7 and #H9 subtype potential #pandemic #influenza viruses

 

Abstract

Influenza continues to cause significant mortality globally and possesses substantial pandemic potential. Assessing pandemic risk requires a clear understanding of existing population immunity. Leveraging a unique large-scale cohort of human sera, we evaluated total and neutralising antibody-mediated immunity to multiple haemagglutinin (HA) proteins, including those from subtypes with high pandemic potential. Our analysis reveals that population immunity is heterogeneous, with distinct age-dependent differences in responses to H5, H7, and H9 avian influenza subtypes. These shifts align with historical circulation patterns of seasonal H1N1 and H3N2 human viruses. Notably, H7 viruses are primarily neutralised through head domain epitopes, while H5 viruses are targeted mainly via stem epitopes, although in both instances some neutralisation occurred via receptor binding site-adjacent epitopes. Furthermore, H7 responses were dominated by non-glycan-targeted IgG2 antibodies, whereas H5 responses were primarily IgG1-mediated. These findings highlight varying levels of susceptibility to influenza across the population, supporting vaccination approaches informed by exposure history.

Competing Interest Statement

CPT has received lecture fees from Moderna.

Source: 

Link: https://www.medrxiv.org/content/10.1101/2025.09.08.25335309v2

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#Usutu virus promotes #WNV #replication in #Culex pipiens biotype molestus during simultaneous and sequential #coinfections

 

Abstract

The epidemiological co-circulation of the two flaviviruses West Nile virus (WNV) and Usutu virus (USUV) in several European countries poses the risk of co-infections in vertebrate hosts and mosquito vectors. WNV is an important human pathogen, whereas USUV is primarily relevant in veterinary and wildlife health. Co-infections have been detected in birds and, occasionally, in humans. To determine the potential consequences of co-exposure and co-infections in mosquitoes on viral transmission, lab-reared Culex pipiens biotype molestus were orally infected with both viruses either simultaneously or sequentially at 7-day intervals with German isolates of WNV lineage 2 and USUV lineage Europe 3. Simultaneous exposure resulted in a significantly increased WNV infection rate, while infection and transmission of USUV were inhibited at the same time. During sequential exposure, prior WNV exposure also had a negative effect on susceptibility to USUV, whereas conversely, WNV infection rates were not altered by prior USUV exposure. Furthermore, mosquitoes with established co-infections after simultaneous co-exposure exhibited higher WNV viral loads than those infected exclusively with WNV. The study reveals complex interactions between WNV, USUV, and the mosquito vector, which could influence vector competence and vector capacity of Culex pipiens biotype molestus in areas with co-circulation of WNV and USUV.

Source: 

Link: https://doi.org/10.1371/journal.ppat.1014601

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Characteristics and #Superspreading #Potential of #Andes Virus Person-to-Person #Transmission

 

Abstract

By using historical contact tracing data, we estimated that 23.4% of case-patients caused 80% of Andes virus (ANDV) person-to-person transmission. We demonstrated a low but nonnegligible probability of observing a large-scale ANDV infection outbreak in a rodent-free setting consisting of close contacts, despite the historically self-limited person-to-person transmission of ANDV.

Source: 

Link: https://doi.org/10.3201/eid3210.260908

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#Bundibugyo virus gp seroreactivity following recombinant VSV–Zaire Ebola virus gp #vaccination in #outbreak-affected populations of #DRC: a longitudinal cohort study

 

Summary

Background

There are currently no licensed vaccines for disease caused by Bundibugyo virus (BDBV). The recombinant vesicular stomatitis virus–Zaire Ebola virus glycoprotein (rVSVΔG-ZEBOV-GP) vaccine has been widely deployed during Ebola virus disease outbreaks caused by Ebola virus (EBOV). Human studies have shown cross-reactive BDBV antibody responses following licensed Ebola virus disease vaccine administration, but the durability and longitudinal kinetics of these responses in populations vaccinated during outbreaks remain unknown. We aimed to evaluate BDBV glycoprotein seroreactivity following rVSVΔG-ZEBOV-GP vaccination in two longitudinal cohorts from regions of the Democratic Republic of the Congo affected by Ebola virus disease outbreaks.

Methods

This longitudinal cohort study was done in Mbandaka, Equateur Province, and Beni, North Kivu Province. Individuals aged 1 year and older who received the rVSVΔG-ZEBOV-GP vaccine under the WHO ring-vaccination protocol were eligible for enrolment. These populations were defined as: people with confirmed Ebola virus disease, contacts of people with Ebola virus disease or contacts-of-contacts, and health-care or front-line workers in areas affected by Ebola virus disease. Participants were enrolled from June 2 to July 3, 2018, in Mbandaka and from Aug 15 to 29, 2018, in Beni. Serum samples were collected from vaccine recipients and antibody reactivity was assessed using a multiplex pan-filovirus immunoassay. Both cohorts were followed up over 5 years, with seven data collection periods in each province. We evaluated longitudinal trends in EBOV and BDBV glycoprotein seroreactivity using a pan-filovirus multiplex immunoassay across follow-up visits.

Findings

We analysed 5849 serum samples from 1081 participants. 715 (66%) of 1081 participants were male and 366 (34%) were female. BDBV glycoprotein seroreactivity differed substantially between study sites. At baseline, 16 (3%) of 482 participants in Mbandaka and 62 (10%) of 599 in Beni were seroreactive to BDBV glycoprotein. In Mbandaka, BDBV glycoprotein antibody reactivity remained stable through to 6 months after initial vaccination before increasing from a mean median fluorescent intensity (MFI) of 1238 (SD 1599) at 2·5 years, with 16 (5%) of 355 seroreactive, to 4845 (5881) at 3·5 years and 116 (35%) of 329 seroreactive (p<0·0001), followed by waning at later visits. In Beni, BDBV glycoprotein antibody reactivity increased rapidly after the initial vaccination, with seroreactivity peaking at 21 days to a mean MFI of 6678 (SD 6997) with 283 (52%) of 541 participants seroreactive and at 6 months to an MFI of 6852 (6560) with 270 (54%) of 501 seroreactive. Although antibody levels decreased after 6 months, EBOV glycoprotein and BDBV glycoprotein antibody reactivity remained above baseline through to 5 years after vaccination.

Interpretation

The differing patterns of BDBV glycoprotein seroreactivity observed between Beni and Mbandaka warrant further investigation into the epidemiological and immunological factors associated with this seroreactivity, including the epidemiological significance of baseline seroreactivity observed before vaccination. To our knowledge, these findings provide the first longitudinal human data describing BDBV glycoprotein seroreactivity following licensed Ebola virus disease vaccination in populations living in regions now affected by the current outbreak of disease caused by BDBV. They add to the growing body of human evidence describing cross-reactive antibody responses following licensed Ebola virus disease vaccination and support rigorous clinical evaluation of rVSVΔG-ZEBOV-GP during the ongoing outbreak while BDBV-specific vaccines continue to be developed.

Funding

The US Food and Drug Administration, the Gates Foundation, and the US Defense Advanced Research Projects Agency.

Source: 

Link: https://doi.org/10.1016/S0140-6736(26)01608-9

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Establishment of an avian #influenza #surveillance program in #Australia's largest #river basin

 

Abstract

To-date Australia has had mostly coastal occurrences in a small but growing number of species of high pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b. The potential impacts of expected spread are the focus of significant preparation activities. Here we report on early surveillance undertaken in 2025-26 in the Murray-Darling Basin, Australia's largest river system, which contains internationally important wetlands that support large multi-species aggregations of waterbirds vulnerable to mass mortality. We detected two low pathogenicity avian influenza (LPAI) viruses of Australian origin in wild waterbirds. Ongoing surveillance will aid in early detection and rapid response in the case of a major inland outbreak of H5N1.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Department of Climate Change, Energy, the Environment and Water

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.09.09.750291v1

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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

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Toward #medical #countermeasures against #hantaviruses

 

Abstract

Hantaviruses are zoonotic threats that can cause hemorrhagic fever with renal syndrome and severe cardiopulmonary syndrome. Despite disease severity, there are no approved vaccines or therapeutics available for the prevention or management of hantavirus infections. Here, we discuss advances in the development of vaccines, neutralizing antibodies, and small-molecule antiviral therapeutics.

Source: 

Link: https://doi.org/10.1016/j.chom.2026.08.002

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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

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Autochthonous #chikungunya virus (CHIKV) #outbreak in province of #Modena, Emilia-Romagna region, #Italy, August to October 2025: #epidemiology, clinical features and virological findings

 

Abstract

Between 10 August and 31 October 2025, 343 cases (306 confirmed and 37 probable) of symptomatic autochthonous chikungunya virus (CHIKV) infection were notified in eight municipalities in the province of Modena, Emilia-Romagna region, northern Italy. The infection was diagnosed by detection of CHIKV RNA in blood and urine samples, and by detection of IgM antibodies against CHIKV. Most common symptoms were arthralgia (n = 326) and fever (n = 317). No fatalities were reported. Chikungunya virus RNA was detected in 39 (14.8%) of 263 pools of Aedes albopictus mosquitoes, thereby confirming local vector-borne transmission. Sequences from 11 case samples and two mosquito pools were whole genome sequenced. The viral strain belonged to the East/Central/South African (ECSA) lineage 2 and was closely related to the strains circulating in Reunion Island in 2024–25. The public health response included rapid vector control measures, reinforced epidemiological surveillance and multidisciplinary coordination between public health authorities and clinicians, laboratories and entomologists. This was one of the largest autochthonous CHIKV outbreaks ever recorded in a temperate European region. It highlights the critical importance of integrated, multidisciplinary preparedness and response for arboviral threats in non-endemic areas.

© 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.2026.31.36.2500962

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#Genomic characterization of Lao #Mobatvirus strains reveals host-associated clustering in Southeast Asian #bats

 

ABSTRACT

While members of the genus Orthohantavirus are well-established human pathogens, the zoonotic potential of bat-associated hantavirids, particularly those within the genus Mobatvirus, remains largely unresolved. To investigate the genetic diversity of these lineages in Southeast Asia, we conducted an expanded surveillance programme in Lao PDR from May 2023 to October 2025 in bat populations and wild animals from local wet markets. Using molecular screening and deep sequencing to characterize hantavirids from bat populations and wild animals from local wet markets, we identified 20 positive samples across four bat species, recovering coding-complete genomes for multiple novel variants. Phylogenetic analysis confirmed that these viruses clustered within Mobatvirus, resolving into two major subclades. The first subclade clustered with Quezon and Robina viruses found in fruit-eating bats. The second subclade further split into two lineages corresponding to Ðakrông and Xuân Sơn viruses, which are associated with trident and leaf-nosed bats, respectively. Despite the strong host association observed, the detection of these viruses in a wet market highlights this setting as a potential human exposure interface. These findings significantly expand the known diversity of mobatviruses in Laos and highlight the urgent need for serological surveillance in at-risk human populations to assess the potential for spillover.

Source: 

Link: https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002333

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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

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#Risk factors for #hospital admission and #mortality in patients with #influenza virus #infection: a systematic review and meta-analysis

 

Summary

Background

Identifying risk factors associated with hospital admission and mortality in patients with influenza is crucial for guiding clinical management and public health strategies. To support an update of WHO influenza clinical guidelines, this systematic review and meta-analysis assessed risk factors for hospital admission and all-cause mortality in patients with seasonal influenza.

Methods

We systematically searched Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Global Health for observational studies published from Jan 1, 2000, until Oct 30, 2025, that enrolled patients of any age with laboratory-confirmed seasonal influenza and reported an adjusted effect estimate for the association between at least one risk factor and hospital admission or all-cause mortality, or both. We conducted inverse-variance random-effects model meta-analyses to summarise the evidence and assessed the certainty of evidence using the GRADE approach. We registered the protocol with PROSPERO, CRD42024535669.

Findings

We identified 35 808 records, of which 63 studies enrolling 2 150 518 participants (mean age 3·6–87·9 years) were eligible. In patients with non-severe influenza, evidence with moderate or high certainty showed that older age (odds ratio 1·72 per 10-year increase for adults [95% CI 1·02–2·89]); cardiovascular disease (2·72 [1·24–5·94]); HIV, immunodeficiency, or immunosuppression (2·70 [1·55–4·70]); chronic respiratory disease (2·24 [1·90–2·64]); and any neurological disease (2·31 [1·65–3·24]) were major risk factors for hospital admission—pregnancy (1·88 [1·73–2·05]), diabetes (1·84 [1·26–2·67]), and malignancy (1·75 [1·12–2·75]) were additional risk factors for hospital admission. In patients with severe influenza, evidence with moderate or high certainty showed that secondary bacterial infection (4·13 [1·53–11·14]), malnutrition (3·29 [1·57–6·89]), sepsis (3·19 [2·08–4·89]), acute kidney injury (2·92 [1·11–7·73]), age 65 years or older (2·47 [2·21–2·75]), chronic cardiovascular disease (2·43 [1·16–5·09]), malignancy (2·21 [1·31–3·72]), and chronic neurological disease (2·08 [1·13–3·83]) were major risk factors for all-cause mortality—any liver disease (1·86 [1·35–2·58]); HIV, immunodeficiency, or immunosuppression (1·79 [1·51–2·13]), and chronic obstructive pulmonary disease (1·74 [1·37–2·20]) were additional risk factors for all-cause mortality.

Interpretation

Age 65 years or older, immunocompromised status, cardiovascular disease, neurological disease, and chronic respiratory disease are major risk factors for hospital admission in patients with non-severe seasonal influenza. Secondary bacterial infection, malnutrition, sepsis, acute kidney injury, age 65 years or older, chronic cardiovascular disease, malignancy, and chronic neurological disease are major risk factors for all-cause mortality in patients with severe seasonal influenza. Our findings support risk stratification and targeted prevention and treatment strategies for seasonal influenza.

Funding

WHO.

Source: 

Link: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00195-5/abstract?rss=yes

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Increased #receptor #binding and #spike #glycosylation, remodeled immune escape of surging #SARS-CoV-2 subvariant BA.3.2.2/RE.2.2/Cicada

 

Significance

SARS-CoV-2 evolved into distinct phylogenetic clades, generating a series of mutant strains. Notably, variants such as BA.1, BA.2.86, and BA.3.2 deserve special attention as they emerged abruptly at high detection frequencies during specific periods and harbored extensive mutations in the spike protein relative to contemporaneously prevalent strains, often accompanied by unique phenotypic characteristics. In this study, we primarily evaluated the structural and functional features of the BA.3.2.2 S protein, revealing its distinct traits in receptor binding, immune evasion, cross-species transmission, and glycosylation evolution. We observed constrained viral immune escape, as certain antibodies that were nonneutralizing against previously dominant subvariants exhibited neutralizing activity against recently emerged BA.3.2.2. These findings provide mechanistic insights for viral surveillance, vaccines, and therapeutics development.

Abstract

SARS-CoV-2 continues to evolve. The subvariant BA.3.2 (Cicada), a derivative of the Omicron BA.3 subtype first detected in late 2024, harbors multiple spike protein mutations, ORF7 and ORF8 deletions, and has recently evolved sublineages (BA.3.2.1 and BA.3.2.2), rendering it a critical target for epidemiological surveillance. The BA.3.2.2 sublineage, represented by RE.2.2, shows a marked upward trend in late 2025. Using surface plasmon resonance, we found that RE.2.2’s spike (S) protein receptor-binding domain (RBD) exhibits relatively high affinity for human receptor angiotensin-converting enzyme 2, with structural analysis identifying the R493Q reverse mutation as the key determinant. Pseudovirus infection and antibody neutralization assays demonstrated that RE.2.2 exhibited a distinct neutralization profile compared to contemporaneous dominant subvariants. Notably, several antibodies that previously lacked neutralizing activity (e.g., S2K146 and L4.65) to other subvariants regained neutralizing potency against RE.2.2, which was associated with key mutations including G446D. Profiling of RE.2.2 RBD binding to ACE2 orthologs across species showed no significant difference in species tropism from the representative Omicron BA.1. Importantly, RE.2.2 exhibits the newly emerged N-linked glycosylation at spike protein N529 (absent in all other subvariants), a modification potentially associated with immune evasion or spike protein conformational dynamics. In addition, we corroborated the “O-follow-N” glycosylation observation as previously reported, where O-linked glycans preferentially localize near N-glycosylation sites, implying coordinated glycan organization as an extra layer of spike regulation. These findings illuminate the evolutionary characteristics, functional changes, and the constrained virus immune escape of BA.3.2.2 (RE.2.2), providing critical insights into antibody development and variant surveillance.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2614163123

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