#Czech Republic - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

Sudden death of birds, clinical signs, non-commercial hobby flock of hens, products are used exclusively for own consumption in the same household.

Source: WOAH, https://wahis.woah.org/#/in-review/6471

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Novel #Orthohantavirus Associated with #Hantavirus Pulmonary Syndrome in Northern #Argentina

Abstract

In this work, we performed the genetic characterization of a new variant of orthohantavirus associated with a fatal case of hantavirus pulmonary syndrome, outside the known endemic region, in northwestern Argentina. We first confirmed an orthohantavirus infection by ELISA, testing for the detection of IgM and IgG antibodies. Then, we extracted RNA from 100 microliters of serum, the only sample available, followed by RT-PCR. The amplicons were sequenced using Sanger and next-generation sequencing technology. We obtained partial sequences of 1253 bp, 799 bp and 1675 bp from the S-, M- and L-segments, respectively, showing low sequence identities with all the previously characterized hantaviruses (10.9%, 13.5% and 15.1% of the divergence, respectively). The phylogenetic analysis showed that this virus belongs to the Orthohantavirus andesense species (ANDV), and among the ANDV-like variants, it is more closely related to the Lechiguanas clade. Similar percentages of divergence were considered sufficient to distinguish AND-like variants in previous works. As the patient had no travel history before the onset of disease was reported, we conducted rodent surveys to confirm the presence of reservoirs. The rodent assemblage was compatible with the transitional zone among different ecoregions (Yungas, Chaco and Monte). Moreover, one of the species captured, Oligoryzomys flavescens, was previously described as a reservoir of hantavirus. This species may either host several variants across its range or encompass a species complex, as proposed by some authors.

Source: Viruses, https://www.mdpi.com/1999-4915/17/5/717

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Yellow fever - Region of the #Americas (#WHO D.O.N., May 16 '25)

{Summary}

Situation at a glance

From 29 December 2024 and as of 26 April 2025 (with data for Ecuador updated as of 2 May 2025), a total of 212 confirmed human cases of yellow fever, including 85 deaths, have been reported to WHO by five countries in the Region of the Americas (case fatality rate (CFR) 40%). 

The cases have been reported in the Plurinational State of Bolivia, Brazil, Colombia, Ecuador and Peru. 

The 212 confirmed yellow fever cases reported so far in 2025 represent a threefold increase compared to the 61 confirmed cases reported in 2024. 

WHO is supporting affected countries in implementing coordinated actions to respond to the yellow fever cases and outbreaks. 

This includes: 

- enhancing preventive measures, 

- strengthening surveillance and case management, 

- improving risk communication and community engagement, and 

- implementing immunization activities. 

The current yellow fever situation in the Americas is driven by increased sylvatic transmission cycles. 

The occurrence of yellow fever cases outside of the Amazon basin, combined with high fatality, varying vaccination coverage across affected countries, and limited vaccine supply, contributes to the overall classification of yellow fever risk in the Region of the Americas, especially in endemic countries, as high. 

WHO emphasizes the importance of active surveillance, timely laboratory testing, cross-border coordination, and information sharing. 

Vaccination remains the primary means for the prevention and control of yellow fever. 

WHO continues to support countries in expanding vaccination coverage through routine immunization programs and mass vaccination campaigns to enhance population immunity and reduce the risk of outbreaks.

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON570

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (CDC, May 16 '25)

 

{Excerpt}

Time Period: April 27, 2025 - May 03, 2025

-- H5 Detection: 8 sites (2.0%)

- No Detection: 402 sites (98.0%)

- No samples in last week: 67 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html

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#Molnupiravir or #nirmatrelvir–ritonavir plus usual care vs usual care alone in patients admitted to #hospital with #COVID19 (RECOVERY)...

Summary

Background

Molnupiravir and nirmatrelvir–ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce.

Methods

The RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19. In this study we report the molnupiravir and nirmatrelvir–ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia; the nirmatrelvir–ritonavir comparison was conducted at 32 hospitals in the UK. Participants could take part in both comparisons. The primary outcome was 28-day mortality, and secondary outcomes were time to discharge alive from hospital and progression to invasive ventilation or death. Analysis was by intention to treat. Both comparisons were stopped because of low recruitment. This study is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

From Jan 24, 2022, to May 24, 2023, 923 participants were recruited to the molnupiravir comparison (445 allocated to molnupiravir and 478 to usual care), and from March 31, 2022, to May 24, 2023, 137 participants were recruited to the nirmatrelvir–ritonavir comparison (68 allocated to nirmatrelvir–ritonavir and 69 to usual care). More than three-quarters of participants were vaccinated and had antispike antibodies at randomisation, and more than two-thirds were receiving other SARS-CoV-2 antivirals. In the molnupiravir comparison, 74 (17%) participants allocated to molnupiravir and 79 (17%) allocated to usual care died within 28 days (hazard ratio [HR] 0·93 [95% CI 0·68–1·28], p=0·66). In the nirmatrelvir–ritonavir comparison, 13 (19%) participants allocated to nirmatrelvir–ritonavir and 13 (19%) allocated to usual care died within 28 days (HR 1·02 [0·47–2·23], p=0·96). In neither comparison was there evidence of any difference in the duration of hospitalisation or the proportion of participants progressing to invasive ventilation or death.

Interpretation

Adding molnupiravir or nirmatrelvir–ritonavir to usual care was not associated with improvements in clinical outcomes. However, low recruitment meant a clinically meaningful benefit of treatment could not be ruled out, particularly for nirmatrelvir–ritonavir.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00093-3/fulltext?rss=yes

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Identification of naturally occurring #drug-resistant #mutations of #SARS-CoV-2 papain-like #protease

Abstract

The SARS-CoV-2 papain-like protease (PLpro) is a cysteine protease that cleaves viral polyproteins and antagonizes the host immune response during viral replication. Jun12682 and PF-07957472 are the first-in-class PLpro inhibitors showing potent in vivo antiviral efficacy in mouse models. In this study, we characterize naturally occurring mutations at residues located at the drug-binding site of Jun12682. The results reveal several PLpro mutants showing significant drug resistance while maintaining comparable enzymatic activity as the wild-type PLpro. The physiological relevance of the identified drug-resistant mutants, including E167G and Q269H, is validated through independent serial viral passage experiments. Molecular dynamics simulations and perturbative free energy calculations show that drug-resistant PLpro mutants weaken hydrogen bonding and π-π stacking interactions. Collectively, this study identifies E167, Y268, and Q269 as drug-resistant hotspots for PLpro inhibitors that bind to the BL2 loop and groove region, which are valuable in informing the design of the next-generation PLpro inhibitors.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-59922-9

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Molecular basis of #influenza #ribonucleoprotein complex #assembly and processive #RNA synthesis

Abstract

Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electron tomography, we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove. Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states, revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors. These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development.

Source: Science, https://www.science.org/doi/10.1126/science.adq7597

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#Statement on the #antigen #composition of #COVID19 #vaccines (#WHO, May 15 '25)

 

Key points

-- Vaccination remains an important public health countermeasure against COVID-19. As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO Strategic Advisory Group of Experts on Immunization (SAGE).

-- SARS-CoV-2 continues to undergo sustained evolution since its emergence in humans, with important genetic and antigenic changes in the spike protein.

-- The objective of an update to COVID-19 vaccine antigen composition is to enhance vaccine-induced immune responses to circulating SARS-CoV-2 variants.

-- The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) advises manufacturers that monovalent JN.1 or KP.2 vaccines remain appropriate vaccine antigens; monovalent LP.8.1 is a suitable alternative vaccine antigen.

-- In accordance with WHO SAGE policy, vaccination should not be delayed in anticipation of access to vaccines with an updated composition.

The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) continues to closely monitor the genetic and antigenic evolution of SARS-CoV-2 variants, immune responses to SARS-CoV-2 infection and COVID-19 vaccination, and the performance of COVID-19 vaccines against circulating variants. 

Based on these evaluations, WHO advises vaccine manufacturers and regulatory authorities on the implications for future updates to COVID-19 vaccine antigen composition. 

In April 2024, the TAG-CO-VAC recommended the use of a monovalent JN.1 lineage vaccine antigen as one approach to induce enhanced neutralizing antibody responses to JN.1 and its descendent lineages. 

In December 2024, the TAG-CO-VAC advised retaining the use of a monovalent JN.1 lineage vaccine antigen. 

Multiple manufacturers (using mRNA, recombinant protein-based, and adenovirus-vectored platforms) have updated COVID-19 vaccine antigen composition to monovalent JN.1 lineage formulations (JN.1 or KP.2). 

Several of these vaccines have been approved for use by regulatory authorities and introduced into vaccination programmes in some countries during the second half of 2024. Previous statements from the TAG-CO-VAC can be found on the WHO website.

The TAG-CO-VAC reconvened on 6-7 May 2025 to review: 

- the genetic and antigenic evolution of SARS-CoV-2; 

- immune responses to SARS-CoV-2 infection and/or COVID-19 vaccination; 

- the performance of currently approved vaccines against circulating SARS-CoV-2 variants; and 

- the implications for COVID-19 vaccine antigen composition.

Evidence reviewed

The published and unpublished evidence reviewed by the TAG-CO-VAC included: 

(1) SARS-CoV-2 genetic evolution with additional support from the WHO Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE); 

(2) Antigenic characterization of previous and emerging SARS-CoV-2 variants using virus neutralization tests with animal antisera and further analysis of antigenic relationships using antigenic cartography; 

(3) Immunogenicity data on the breadth of neutralizing antibody responses elicited by currently approved vaccine antigens against circulating SARS-CoV-2 variants using animal and human sera; 

(4) Preliminary immunogenicity data on immune responses following infection with circulating SARS-CoV-2 variants; 

(5) Available vaccine effectiveness (VE) estimates of currently approved vaccines during periods of JN.1 lineage circulation; and 

(6) Preliminary non-clinical and clinical immunogenicity data on the performance of candidate vaccines with updated antigens shared confidentially by vaccine manufacturers with TAG-CO-VAC. 

Further details on the data reviewed by the TAG-CO-VAC can be found in the accompanying data annex. Confidential data reviewed by the TAG-CO-VAC are not shown.

Summary of available evidence

There are persistent and increasing gaps in the reporting of cases, hospitalizations and deaths, from WHO Member States, making epidemiological trends difficult to infer. 

Nonetheless, in 2025, SARS-CoV-2 continues to circulate globally, causing severe disease, post COVID-19 condition, and death. 

The majority of COVID-19 deaths continue to occur in individuals aged 65 years and older and those with coexisting conditions. 

Some countries have reported an increase in incidence of COVID-19-related hospitalizations and deaths among children under 1 year of age, as compared to young adults, although this group still accounts for a small proportion of total COVID-19 hospitalizations and deaths.

As of May 2025, currently circulating SARS-CoV-2 variants are derived from JN.1. 

The weekly proportion of Variant Under Monitoring (VUM) LP.8.1 among all SARS-CoV-2 sequences submitted to GISAID continues to increase. 

The weekly proportion of JN.1 (Variant of Interest, VOI) is slowly increasing, largely due to increases in LF.7 and its descendent variants, while all other VUMs (KP.3, KP.3.1.1, XEC, and LB.1) are declining. 

Several JN.1 derived variants have independently evolved changes in the spike protein at epitopes known to be targeted by neutralizing antibodies.

Published and unpublished data using antisera from naïve hamsters infected with JN.1, KP.2, KP.3.1.1, XEC or LP.8.1 or mice immunized with mRNA vaccine antigens JN.1, KP.2 or KP.3 showed that JN.1, KP.2, KP.3.1.1, XEC, and LP.8.1 are antigenically closely related to each other (approximately 1 antigenic unit in cartographic analysis, which corresponds to a two-fold-difference in neutralization).

In published and unpublished data from humans, vaccination with monovalent JN.1 or KP.2 antigens significantly increased neutralizing antibody titers against all JN.1 descendent lineages tested:

-- Analysis of pre- and post-vaccination sera from JN.1 lineage (i.e. JN.1 or KP.2) immunized individuals demonstrated significant rises in neutralization of JN.1 and its descendent lineages, including KP.3.1.1, XEC, LF.7.2.1, and LP.8.1.

-- Neutralization titers against LP.8.1 were generally modestly lower (2-fold reduction) than those against the homologous JN.1 or KP.2 antigen.

Contemporary vaccine effectiveness (VE) estimates are relative (rVE), rather than absolute (comparing vaccinated to unvaccinated individuals), and demonstrate the added or incremental protection of recent vaccination over and above pre-existing infection- and vaccine-derived immunity. 

Monovalent JN.1 or KP.2 COVID-19 vaccines were introduced into some vaccination programmes in the second half of 2024. There are only a few studies estimating rVE for the monovalent JN.1 or KP.2 mRNA COVID-19 vaccines during periods of JN.1 descendent lineage circulation. 

Both vaccines demonstrated additional protection—relative to pre-existing immunity—against symptomatic and severe COVID-19 during the first three to four months after vaccination.

Data shared confidentially with the TAG-CO-VAC by vaccine manufacturers showed that:

-- Immunization of naïve mice, as well as of mice previously immunized with SARS-CoV-2 variants, with monovalent JN.1 or KP.2 vaccines resulted in high neutralizing antibody titers against JN.1 and its derivatives including KP.2, KP.3.1.1, XEC, LP.8.1, and LF.7.2. However, neutralization titers against LP.8.1 were typically lower than those against the homologous immunizing antigen.

-- Immunization of naïve mice, as well as of mice previously immunized with SARS-CoV-2 variants, with monovalent LP.8.1 vaccine candidates elicited high neutralizing antibody titers against the homologous antigen. Cross-neutralizing antibody titers elicited against other JN.1 lineage variants including JN.1, KP.2, KP.3, KP.3.1.1, XEC, and LF.7.2 were similar or modestly higher than those elicited by JN.1 or KP.2 antigens.

-- In humans, vaccination with monovalent JN.1 or KP.2 antigens resulted in robust neutralizing antibody responses to JN.1 and descendent variants, including KP.3.1.1, XEC, LP.8.1, and LF.7.2.

As in non-clinical data, analysis of pre- and post-vaccination sera from JN.1 or KP.2 immunized individuals showed some variation in neutralizing antibody titers against LP.8.1 and LF.7.2 across different studies. In most instances, they were similar or lower than those against the homologous JN.1 or KP.2 antigens.

Overall, the currently approved monovalent JN.1 or KP.2 vaccines continue to elicit broadly cross-reactive immune responses to circulating JN.1-derived variants. 

LP.8.1 as a vaccine antigen offers similar or modestly increased cross-reactive antibody responses to circulating JN.1-derived variants, as compared to monovalent JN.1 or KP.2 vaccines. Mathematical modeling indicates that an increase in neutralizing antibody titers may translate into an improvement in vaccine effectiveness and duration of protection.

The TAG-CO-VAC acknowledges several limitations of available data: 

-- There are persistent and increasing gaps in the reporting of cases, hospitalizations and deaths, from WHO Member States, as well as in genetic/genomic surveillance of SARS-CoV-2 globally, including low numbers of samples sequenced and limited geographic diversity. The TAG-CO-VAC strongly supports the ongoing work of the WHO Coronavirus Network (CoViNet) and the Global Influenza Surveillance and Response System (GISRS) to address this information gap.

-- The timing, specific mutations and antigenic characteristics of emerging and future variants are difficult to predict, and the potential public health impact of these variants remain unknown. There are JN.1-derived variants and long branch saltation variants that are currently detected in low or very low proportions, and which will continue to be monitored and/or characterized. The TAG-CO-VAC strongly supports the ongoing work of the TAG-VE. 

-- Although neutralizing antibody titers have been shown to be important correlates of protection from SARS-CoV-2 infection and of estimates of vaccine effectiveness, there are multiple components of immune protection elicited by infection and/or vaccination. Data on the immune responses following JN.1 descendent lineage infection or monovalent JN.1 or KP.2 vaccination are largely restricted to neutralizing antibodies. Data and interpretation of other aspects of the immune response, including cellular immunity, are limited. 

-- Immunogenicity data against currently circulating SARS-CoV-2 variants are not available for all COVID-19 vaccines. 

-- Estimates of rVE against recently circulating JN.1 variants are limited in terms of the number of studies, geographic diversity, vaccine platforms evaluated, populations assessed, duration of follow-up, and contemporary comparisons of vaccines with different antigen composition.

Recommendations for COVID-19 vaccine antigen composition

-- Monovalent JN.1 (NextStrain: 24A, GenBank: PP298019, GISAID: EPI_ISL_18872762) or KP.2 vaccines remain appropriate for ongoing use; monovalent LP.8.1 (NextStrain: 25A; GenBank: PV074550.1; GISAID: EPI_ISL_19467828) is a suitable alternative vaccine antigen.

Other approaches that demonstrate broad and robust neutralizing antibody responses or efficacy against currently circulating JN.1 descendent lineage variants could also be considered.

As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO SAGE. Vaccination should not be delayed in anticipation of access to vaccines with an updated composition.

Further data requested

Given the limitations of the evidence upon which the recommendations above are derived and the anticipated continued evolution of the virus, the TAG-CO-VAC strongly encourages generation of the following data (in addition to the types of data outlined in March 2025): 

-- Immune responses and clinical endpoints (i.e. VE and/or comparator rates of infection and severe disease) in varied human populations who receive currently approved COVID-19 vaccines against emerging SARS-CoV-2 variants, across different vaccine platforms.

-- Strengthened epidemiological and virological surveillance, as per the Standing Recommendations for COVID-19 in accordance with the International Health Regulations (2005), to determine if emerging variants are antigenically distinct and able to displace circulating variants.

-- Strengthened epidemiological surveillance to characterize disease severity in immunologically naïve and/ or immature individuals (i.e. birth cohorts).

-- Clinical evaluation of relevant new vaccine antigens derived from more recent SARS-CoV-2 variants.

As previously stated, the TAG-CO-VAC continues to encourage the further development of vaccines that may improve protection against infection and reduce transmission of SARS-CoV-2.

The TAG-CO-VAC will continue to closely monitor the genetic and antigenic evolution of SARS-CoV-2 variants, immune responses to SARS-CoV-2 infection and COVID-19 vaccination, and the performance of COVID-19 vaccines against circulating variants. The TAG-CO-VAC will also continue to reconvene every six months, or as needed, to evaluate the implications for COVID-19 vaccine antigen composition. At each meeting, recommendations to either maintain current vaccine composition or to consider updates will be issued. Prior to each meeting, the TAG-CO-VAC will publish an update to the statement on the types of data requested to inform COVID-19 vaccine antigen composition deliberations.

Source: World Health Organization, https://www.who.int/news/item/15-05-2025-statement-on-the-antigen-composition-of-covid-19-vaccines

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Genetic diversity of #H5N1 avian #influenza viruses isolated from #birds and #seals in #Russia in 2023

Abstract

Thousands of outbreaks of the highly pathogenic avian influenza A(H5N1) virus in birds and an increasing number of mammal infections are registered annually. In 2023, multiple avian influenza outbreaks were registered among wild birds, poultry and seals in Russia. The genetic characterization of seventy-seven avian viruses and three viruses from seals showed that they belonged to the 2.3.4.4b clade and represented four distinct reassortant genotypes. The majority of viruses represented genotype BB, which was widespread in Europe in 2023. Viruses from seals and four viruses from birds, isolated from outbreaks in the Far East region, belonged to the G1 (A3) genotype and had the amino acid substitution N319K in the NP protein, previously associated with an increased virulence for mammals. In addition, one virus of the G10 genotype and two viruses, representing a previously undescribed genotype (designated as Ru-23-G4) were identified. The viruses analyzed showed normal inhibition by neuraminidase inhibitors. Seven viruses had genetic markers of amantadine resistance. All the influenza A(H5N1) viruses studied showed a binding preference for α2-3-linked sialic acids, suggesting a low risk of transmission among humans. Nevertheless, monitoring of reassortment and mammalian adaptation mutations is essential for the timely identification of viruses with increased pandemic potential.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-00417-4

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#Investigation of #Influenza #H5N1 Virus #Neutralization by Quadrivalent Seasonal #Vaccines, #UK, 2021–2024

Abstract

We tested cross-neutralization against highly pathogenic avian influenza A(H5N1) virus in adults vaccinated with 2021–2023 seasonal quadrivalent influenza vaccine in the United Kingdom. Seasonal quadrivalent influenza vaccines are unlikely to protect vulnerable persons against severe H5N1 disease during widespread transmission. Enhanced measures are needed to protect vulnerable people from H5N1 virus infection.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/6/24-1796_article

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Emergence of #Antigenic #Variants in #Bovine #H5N1 #Influenza Viruses

ABSTRACT

The recent emergence of the H5N1 influenza virus in dairy cattle has raised significant public health concerns. Using a previously established pseudovirus-based neutralization assay, we evaluated the impact of emerging hemagglutinin (HA) mutations on the efficacy of current candidate vaccine viruses (CVVs). Neutralization analysis revealed that the cow-derived H5N1 virus showed up to a 2.2-fold reduction in sensitivity compared to the CVV homologous neutralization titers. Among the 1,453 HA sequences analyzed from cow-derived H5N1 viruses, we identified four major mutations (E2K, D104G, V147M, and S336N) that emerged after the initial isolation, with 134 isolates (9.22%) harboring all four mutations. These multi-mutation variants exhibited up to a 3.3-fold reduction compared with the CVV homologous neutralization titers. Single-mutation analysis demonstrated that the D104G mutation, present in 47.8% of sequences, markedly contributed to antibody escape. Our findings highlight the importance of continued surveillance and antigenic evaluation of emerging variants for pandemic preparedness strategies.

Source: Journal of Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.70394

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Effects of #JAK #inhibitors in adults admitted to #hospital due to #COVID19: a systematic review and individual participant data meta-analysis of randomised clinical trials

Summary

Background

Evidence from randomised clinical trials (RCTs) of Janus kinase (JAK) inhibitors—compared with usual care or placebo—in adults treated in hospital for COVID-19 is conflicting. We aimed to evaluate the benefits and harms of JAK inhibitors compared with placebo or usual care and whether treatment effects differed between prespecified participant subgroups.

Methods

For this systematic review and individual participant data meta-analysis (IPDMA), we searched Medline via Ovid, Embase via Elsevier, the Cochrane Central Register of Controlled Trials, the Cochrane COVID-19 Study Register, and the COVID-19 L·OVE Platform, including backward and forward citation searching (last search Nov 28, 2024), for RCTs (unpublished or published in any format and any language) that randomly assigned adults (aged ≥16 years) admitted to a hospital due to COVID-19 to receive either a JAK inhibitor (any type) or no JAK inhibitor (ie, received site-specific standard of care with or without placebo), and requested individual participant data (IPD) from the original trial teams. The primary outcome was all-cause mortality at day 28 after random assignment. We used two-stage meta-analyses adjusting for age and respiratory support, and pooled estimates using random-effects models. The assessment of individual-level effect modifiers was based solely on within-trial information and continuous modifiers were investigated as both linear and non-linear interactions. We used the Instrument for Assessing the Credibility of Effect Modification Analyses to appraise the subgroup analyses and the Grading of Recommendations Assessment, Development, and Evaluation approach to adjudicate the certainty of evidence. Grade 3 or 4 adverse events and serious adverse events by day 28, and adverse events of special interest within 28 days, were assessed among secondary outcomes. This study was registered with PROSPERO (CRD42023431817).

Findings

We identified 16 eligible trials. IPD were obtained from 12 trials, corresponding to 12 902 adults admitted to hospital between May, 2020, and March, 2022. These trials represented 12 902 [96·1%] of 13 423 participants from all eligible trials worldwide. Seven trials evaluated baricitinib, three evaluated tofacitinib, and two evaluated ruxolitinib. Overall, 755 (11·7%) of 6465 participants in the JAK inhibitor group died by day 28 compared with 805 (13·2%) of 6108 participants in the no JAK inhibitor group (adjusted odds ratio [aOR] 0·67 [95% CI 0·55–0·82]; high-certainty evidence; 39 fewer per 1000 [95% CI 55 fewer to 21 fewer]). JAK inhibitors decreased the need for new mechanical ventilation or other respiratory support and allowed for faster discharge from hospital by about 1 day. We observed fewer grade 3 and 4 adverse events and serious adverse events in the JAK inhibitor group (14 fewer per 1000 [95% CI 24 fewer to 4 fewer]; moderate-certainty evidence). The rates of adverse events of special interest were similar across both groups. No credible subgroup effect on mortality at day 28 was found for ventilation status, type of JAK inhibitor, presence of comorbidities, timing of treatment initiation after symptom onset, C-reactive protein concentration, or concomitant use of dexamethasone or tocilizumab. We found a moderately credible effect modification by age, with younger participants showing larger relative treatment effects than older participants, but similar absolute treatment effects due to higher baseline risk for older participants.

Interpretation

This IPDMA of RCTs in adults admitted to hospital due to COVID-19 found that JAK inhibitors reduced mortality across all levels of respiratory support, independent of dexamethasone or tocilizumab, and probably decreased serious and severe adverse events compared with no JAK inhibitors.

Source: Lancet Respiratory Medicine, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(25)00055-4/fulltext?rss=yes

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#Measles - #Morocco (#WHO D.O.N., May 13 '25)

{Summary}

Situation at a glance

Since late 2023, Morocco has been experiencing a widespread measles outbreak. Cases have been recorded across all regions of the country, particularly among children and people who are unvaccinated. In response, the Ministry of Health and Social Protection (MOHSP), in collaboration with relevant sectors, activated the National Center for Public Health Emergency Operations, launched urgent catch-up vaccination campaigns, and strengthened surveillance, case management, and risk communication and community engagement efforts. Measles is a highly transmissible viral disease that can lead to severe complications and death. While Morocco has made significant progress toward measles elimination, the disease remains endemic in the country. The overall risk is assessed as moderate at the national level and moderate at the regional level, particularly given the risk of cross-border transmission in areas with low vaccination coverage.

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON568

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#China reported eight new #human cases of #Influenza A #H9N2 and one new case of Influenza A #H10N3 (HK CHP, May 13 '25)

 

{Excerpt}

Avian influenza A(H9N2): 

-- New Cases (New Deaths): 8 (0) 

- Chongqing Municipality: 

- 1) A 67-year-old man with onset on April 18, 2025. 

- Guizhou Province: 

- 2) A one-year-old girl with onset on April 7, 2025. 

- 3) A one-year-old girl with onset on April 15, 2025. 

- Hunan Province: 

- 4) A five-year-old boy with onset on April 1, 2025.

- 5) A seven-year-old girl with onset on April 1, 2025. 

- 6) A one-year-old girl with onset on April 3, 2025. 

- 7) A five-year-old boy with onset on April 19, 2025

- Yunnan Province:

- 8) A one-year-old girl with onset on April 2, 2025

Avian influenza A(H10N3): 

- Guangxi Zhuang Autonomous Region: 

- 1) A 68-year-old woman with onset on April 13, 2025. 

(...)

Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk19.pdf

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#Philippines - High pathogenicity avian #influenza #H5N9 viruses (#poultry) (Inf. with) - Immediate notification

The affected population are ducks grazing in a rice field situated within Camaligan, Camarines Sur where they may have come into contact with wild birds carrying the virus.

Source: WOAH, https://wahis.woah.org/#/in-review/6473

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Effectiveness of integrated #vector #management on the incidence of #dengue in urban #Malaysia: a cluster-randomised controlled trial

Summary

Background

Malaysia is one of the southeast Asian countries hardest hit by dengue. We implemented a proactive integrated vector management (IVM) approach in a large non-blinded, cluster-randomised controlled trial to quantify its effectiveness on dengue incidence in urban settings.

Methods

In this cluster-randomised controlled trial we enrolled low-cost and medium-cost residential housing blocks in the Federal Territory of Kuala Lumpur and Putrajaya with recurrent dengue outbreaks. Of the 329 eligible sites, 139 were randomly allocated to receive IVM measures (community engagement, targeted outdoor residual spraying using K-Othrine Polyzone, and deployment of autodissemination devices to target both larval and adult mosquitoes) and 141 received routine vector control activities, stratified by block housing cost. The primary outcome was the comparison of dengue incidence between the two groups using information provided by the national e-Dengue surveillance system. Routine vector control activities continued in both control and intervention sites. The trial was retrospectively registered (ISRCTN81915073).

Findings

Between Feb 10, 2020, and Sept 30, 2022, we carried out our IVM approach in the 139 randomly selected intervention sites. 903 834 individuals (447 149 intervention, 456 685 control) were living in the study areas. Dengue was reported in 1434 individuals in the intervention group (mean incidence per 100 person-years of 0·16 [SD 0·18]) compared with 1663 in the control group (0·18 [0·19; risk ratio 0·86, 95% CI 0·70–1·06; p=0·17). No adverse effects were reported.

Interpretation

Our study did not show an effect on the primary endpoint of the overall dengue incidence. Several factors such as substantial decrease in dengue incidence during the COVID-19 pandemic could have reduced the statistical power to detect significant differences between the two groups. Preventive and long-lasting approaches such as our IVM should be further tested to see if targeted interventions could help limit the number of cases in high-risk transmission areas.

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00086-6/abstract?rss=yes

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Dose response comparison of #Nipah virus #strains #Malaysia and #Bangladesh in #hamsters exposed by the intranasal or intraperitoneal route

Abstract

Nipah virus, a zoonotic pathogen, can cause debilitating disease and death in humans. Currently, countermeasures are limited, with several in various stages of testing but none yet FDA-approved for human use. Evaluation of countermeasure candidates requires safety testing in humans, as well as efficacy testing against lethal challenge in animal models. Herein, we describe the characterization and comparison of the intraperitoneal and intranasal Syrian golden hamster models for Nipah virus strains Malaysia and Bangladesh. Overall, the intraperitoneal route of exposure resulted in a more consistent lethal outcome, regardless of virus strain. Therefore, the IP model was subsequently used to evaluate the use of Favipiravir as a potential positive control for future studies investigating NiV countermeasures. In contrast to prior reported results regarding Favipiravir in Nipah virus-infected hamsters, Favipiravir was only fifty percent effective at preventing death following lethal challenge, regardless of Nipah virus strain. The data suggest that Favipiravir is only partially protective against Nipah virus in hamsters, and, thus, would likely not be an ideal candidate as a positive control in future efficacy studies.

Source: PLoS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0318912

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Pregnant Dairy #Heifers Express #Influenza A Virus #Receptors in the Mammary #Gland

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) virus emerged in lactating dairy cattle in March 2024, causing mastitis-related disease and infections in other farm animals and workers. Recent work identified α2,6 and α2,3-linked sialic acids (SA), which serve as influenza virus receptors, in the lactating bovine mammary gland; however, their distribution across stages of mammary growth and development remains unknown. We compared the distribution of tissue sialylation in mammary glands of prepubertal dairy calves, pregnant dairy heifers, and lactating cows. Mammary glands at all physiological stages expressed both α2,6 SA, the preferred receptor linkage for human influenza viruses, and α2,3 SA, the preferred receptor linkage for avian influenza viruses. Importantly, mammary glands of pregnant dairy heifers exhibited the highest overall expression of α2,3 SA, observed in both tissue and alveolar lumens. Our results suggest that pregnant dairy heifers, like lactating dairy cows, are susceptible to H5N1 infection in the mammary gland.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.05.08.652757v1

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Clade 2.3.4.4b Highly pathogenic #H5N1 #influenza viruses from #birds in #China replicate effectively in #bovine cells and pose potential public health #risk

Abstract

In February 2024, H5N1 highly pathogenic avian influenza viruses (HPAIVs) of clade 2.3.4.4b were first reported in dairy cows in the USA. Subsequent multiple outbreaks on dairy farms and sporadic human infections have raised substantial public health concerns. In the same year, four H5N1 HPAIVs of clade 2.3.4.4b were isolated from ducks and geese in live poultry markets (LPMs) spanning seven provinces in China. Evolutionary analysis demonstrated that these viruses had undergone two genetic reassortments with H5 influenza viruses from wild birds in different countries. Except for 565/H5N1, the other three viruses exhibited over 99% genetic homology with avian-origin H5N1 HPAIVs from South Korea and Japan. Notably, 571/H5N1 demonstrated high replication efficiency in bovine-derived cells, particularly in bovine mammary epithelial (MAC-T) cells, and caused 16.7% (1/6) mortality in mice at a dose of 10⁵ EID₅₀/50 μL, indicating its zoonotic potential. Given the potential cross-species transmission risk of H5N1 HPAIVs to cattle herds, we collected 228 serum samples from 12 cattle farms across five provinces and conducted serological testing to investigate seroprevalence of H5N1 HPAIVs in Chinese cattle herds. All tested samples were negative, indicating no widespread infection in the sampled cattle populations. However, infections in cattle from other regions cannot be ruled out. Nevertheless, due to the high mutability of H5N1 HPAIVs, enhanced surveillance of avian influenza viruses is critical to ensure timely responses to potential outbreaks.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2505649

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Middle East respiratory syndrome #coronavirus {#MERS-CoV} - Kingdom of #Saudi Arabia (#WHO D.O.N., May 12 '25)

Situation at a glance

Between 1 March and 21 April 2025, the Ministry of Health (MoH) of the Kingdom of Saudi Arabia (KSA) reported nine cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Two of these cases died. Among the nine cases, a cluster of seven cases were identified in Riyadh, including six health and care workers who acquired the infection from caring for a single infected patient. The cluster was identified through contact tracing and subsequent testing of all contacts, with four of the six health and care workers being asymptomatic and two showing only mild, nonspecific signs. The notification of these cases does not change the overall risk assessment, which remains moderate at both the global and regional levels. These cases show that the virus continues to pose a threat in countries where it is circulating in dromedary camels and spilling over into the human population. WHO recommends implementation of targeted infection prevention and control (IPC) measures to prevent the spread of health-care-associated infections of MERS-CoV and onward human transmission.

Description of the situation

Between 1 March and 21 April 2025, the Ministry of Health (MoH) of the Kingdom of Saudi Arabia (KSA) reported nine cases of MERS-CoV infection. 

The cases were reported from the Hail (1) and Riyadh (8) regions of Saudi Arabia (Figure 1). Of the reported cases, five were male and four were female.

Among these cases, a cluster of seven was identified in Riyadh, including six health and care workers who acquired a nosocomial infection from one single infected patient they had cared for. 

Of the six health and care workers, four remained asymptomatic, while two developed mild, nonspecific symptoms including myalgia, fatigue, nausea and vomiting (...). 

Laboratory confirmation of the cases was performed by real-time polymerase chain reaction (RT-PCR) between 1 March 2025 and 16 April 2025. 

Of the cases, only one had indirect contact with camels and is not a part of the reported cluster. The rest of the patients had no known history of contact with camels or camel products.

Since the first report of MERS-CoV in KSA in 2012, a total 2627 laboratory-confirmed cases of MERS-CoV infection, with 946 associated deaths (Case Fatality Rate or CFR of 36%), have been reported to WHO from 27 countries, across all six WHO regions. 

The majority of cases (2218; 84%), have been reported from KSA, including these newly reported cases (...). Since 2019, no human MERS-CoV infections have been reported from countries outside the Middle East.

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Epidemiology

Middle East respiratory syndrome (MERS) is a respiratory illness caused by a coronavirus (MERS-CoV). The fatality rate among confirmed cases is around 36%, though this may be an overestimate since milder cases often go undetected. The CFR is calculated based solely on laboratory-confirmed infections, which may not reflect the correct mortality rate.

Humans contract MERS-CoV through direct or indirect contact with dromedary camels, the virus’s natural host and zoonotic reservoir. 

Human-to-human transmission occurs via infectious respiratory particles mainly at close distances and also through contact transmission, it has mainly occurred in close-contact situations, particularly in health-care settings. 

Outside these environments, there has been limited documented human-to-human transmission to date. 

MERS can present with no symptoms, mild respiratory issues, or severe illness leading to acute respiratory distress and death. 

Common symptoms include fever, cough, and breathing difficulties, with pneumonia frequently observed, though not always present. 

Some patients also experience gastrointestinal symptoms such as diarrhoea. 

Severe cases may require intensive care, including mechanical ventilation. Those at higher risk of severe outcomes include older adults, individuals with weakened immune systems, and those with chronic conditions like diabetes, kidney disease, cancer, or lung disorders.

The number of MERS-CoV infections reported to WHO has substantially declined since the beginning of the COVID-19 pandemic. 

Initially, this was likely the result of epidemiological surveillance for SARS-CoV-2 being prioritized. 

The similar clinical picture of both diseases may result in reduced testing and detection of MERS-CoV infections. 

However, the Ministry of Health of KSA has been working to improve testing capacities for better detection of MERS-CoV since the easing of the COVID-19 pandemic, with MERS-CoV included into sentinel surveillance testing algorithms since the second quarter of 2023, for samples that test negative for both influenza and SARS-CoV-2. 

In addition, measures taken to reduce SARS-CoV-2 transmission (e.g., IPC measures such as mask-wearing, hand hygiene, physical distancing, improving the ventilation of indoor spaces, respiratory etiquette, stay-at-home orders, reduced mobility) also likely reduced opportunities for onward human-to-human transmission of MERS-CoV. 

Potential cross-protection conferred from infection with or vaccination against SARS-CoV-2 and any reduction in MERS-CoV infection or disease severity and vice versa has been hypothesized but requires further investigation.

No vaccine or specific treatment is currently available, although several MERS-CoV-specific vaccines and therapeutics are in development. Treatment remains supportive, focusing on managing symptoms based on the severity of the illness.

Public health response

The Ministry of Health of KSA implemented the following response measures

-- Infection prevention and control (IPC) measures in healthcare settings:

- Regular training of health and care workers on IPC measures.

- Implementation of stringent IPC measures, including triage protocols, use of personal protective equipment (PPE), and isolation procedures for suspected cases.

- Prompt isolation of cases and quarantine of contacts.

-- Surveillance and testing:

- Rigorous contact tracing and testing of high-risk contacts, including healthcare workers.

- Inclusion of MERS-CoV in sentinel surveillance testing algorithms since 2023.

-- Public health awareness and hygiene practices:

- Public health awareness campaigns to prevent human-to-human transmission.

- Advising people with underlying chronic medical conditions to avoid close contact with animals, particularly dromedaries.

WHO risk assessment

As of 21 April 2025, a total of 2627 laboratory-confirmed cases of MERS-CoV infection have been reported globally to the WHO, with 946 associated deaths. 

The majority of these cases have occurred in countries within the Arabian Peninsula, with 2218 cases (84.4%) and 865 related deaths (CFR 39%) reported from the KSA. 

A notable outbreak outside the Middle East occurred in the Republic of Korea, in May 2015, during which 186 laboratory-confirmed cases (185 in the Republic of Korea and 1 in China) and 38 deaths were reported. However, the index case in that outbreak had a travel history to the Middle East. 

The global case count reflects laboratory-confirmed cases reported to WHO under IHR (2005) or directly by Ministries of Health to date. These numbers may underestimate the true number of cases if some were not reported. The total number of deaths includes those that WHO has been officially informed of, based on follow-up with affected Member States. 

Humans are infected with MERS-CoV from direct or indirect contact with dromedaries who are the natural host and zoonotic source of the MERS-CoV infection. MERS-CoV has demonstrated the ability to be transmitted between humans. 

So far, the observed non-sustained human-to-human transmission has occurred among close contacts and in health care settings. Outside of the healthcare setting there has been limited human-to human transmission.  

The notification of these cases does not change the overall risk assessment. The reported cluster of six secondary cases among health and care workers is the result of rigorous contact tracing and testing performed by KSA, with four of the six cases being asymptomatic and two showing only mild, unspecific signs. 

WHO expects that additional cases of MERS-CoV infection will be reported from the Middle East and/or other countries where MERS-CoV is circulating in dromedaries, and that cases will continue to be exported to other countries by individuals who were exposed to the virus through contact with dromedaries or their products (for example, consumption of raw camel milk), or in a healthcare setting. 

WHO continues to monitor the epidemiological situation and conducts risk assessment based on the latest available information.  

WHO advice

Based on the current situation and available information, WHO reemphasizes the importance of strong surveillance by all Member States for acute respiratory infections, including MERS-CoV where warranted, and to carefully review any unusual patterns. 

Delays in recognizing the early symptoms of MERS-CoV infection, slow triage of suspected cases and delays in implementing IPC measures have been linked with human-to-human transmission of MERS-CoV in health-care settings in past outbreaks. IPC measures are therefore critical to prevent the spread of healthcare-associated infections of MERS-CoV. Health and care workers should always apply standard precautions consistently with all patients, at every interaction in healthcare settings.

Ventilation rates in general patient care rooms should meet or exceed 60 litres per second per patient (or 6 air changes per hour). 

In addition, contact and droplet precautions, which include patient placement in single rooms with dedicated care equipment, and the use of personal protective equipment (PPE) such as clean non-sterile gown, gloves, eye protection and a well-fitting medical mask, should be added to standard precautions when providing care to patients with suspected or confirmed MERS-CoV. 

Airborne precautions should be added when performing aerosol-generating procedures or in settings where aerosol-generating procedures are conducted, including the use of procedure rooms with ventilation rates meeting or exceeding 160 litres per second (or 12 air changes per hour). 

Early identification, case management and prompt isolation of cases, quarantine of contacts, together with appropriate IPC measures in health care settings and public health awareness can prevent human-to-human transmission of MERS-CoV. 

MERS-CoV appears to cause more severe disease in people with underlying chronic medical conditions such as diabetes, renal failure, chronic lung disease, and immunocompromised persons. Therefore, people with these underlying medical conditions should avoid close contact with animals, particularly dromedaries, when visiting farms, markets, or barn areas where the virus may be circulating.

General hygiene measures, such as regular hand washing before and after touching animals and avoiding contact with sick animals, should be adhered to. 

In addition to contact with animals, hygiene practices should be observed when dealing with food items of camels; people should avoid drinking raw camel milk or camel urine or eating meat that has not been properly cooked. 

WHO does not advise special screening at points of entry with regard to this event, nor does it currently recommend the application of any travel or trade restrictions.

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Citable reference: World Health Organization (12 May 2025). Disease Outbreak News; Middle East Respiratory Syndrome coronavirus – Kingdom of Saudi Arabia. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON569

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON569

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