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

{Kauno Region} Information about dead mute swans was received through passive surveillance. The swan was sampled and delivered to the National Reference Laboratory for HPAI detection.

Source: WOAH, https://wahis.woah.org/#/in-review/6414

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Increased #Pneumonia-Related #Emergency Department Visits, Northern #Italy

Abstract

An increase in pneumonia-related emergency department visits was observed in Lombardy, northern Italy, during June–October 2024. Viral causes appear insufficient to explain the increase, suggesting a bacterial cause. Mycoplasma pneumoniae and Bordetella pertussis emerged as possible causes when other surveillance systems were consulted, but the reasons behind this trend remain unknown.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1790_article

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#Mexico: The Ministry of Health reports the #death of the first #human case of avian #influenza A (#H5N1)

{Automatic translation. Edited.} 

www.gob.mx/salud

The Ministry of Health reports the death of the first human case of avian influenza A (H5N1) in Mexico. 

It is reported that a three-year-old girl diagnosed with avian influenza A(H5N1) and a resident of Durango died today at 1:35 a.m. due to respiratory complications resulting from the infection. 

It is a viral disease that affects birds (wild and domestic), mammals and occasionally humans. 

Local, state, and federal health, environmental, and agricultural authorities continue prevention and control measures within the context of One Health. So far, 38 human contacts of the case have been sampled, all of which have tested negative. 

No additional human cases have been identified, and the risk of further cases is considered low. 

X:  @SSalud_mx  

Source: Ministry of Health, https://www.gob.mx/salud/prensa/secretaria-de-salud-informa-la-defuncion-del-primer-caso-humano-de-influenza-aviar-a-h5n1

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A #monoclonal anti-hemagglutinin stem #antibody modified with #zanamivir protects against both #influenza A and B viruses

Significance

Anti-influenza therapeutics remain essential for the control of influenza infections, which may require hospitalization for the most severe cases. Hemagglutinin (HA) and neuraminidase (NA), the two membrane glycoproteins of the influenza virus, play crucial roles in the viral replication cycle. While many monoclonal antibodies and small-molecule inhibitors target HA or NA, each faces limitations tied to their individual properties. We developed an antibody–drug conjugate (ADC) by covalently linking the NA inhibitor zanamivir to MEDI8852, an HA stem-specific monoclonal antibody. The MEDI8852–zanamivir conjugate targets both HA and NA and offers robust and long-lasting protection in mice against lethal infections with influenza A and B viruses. This approach represents an addition to anti-influenza therapy.

Abstract

Influenza remains a significant public health threat. Both monoclonal antibodies and small-molecule inhibitors can target the influenza surface glycoproteins hemagglutinin (HA) or neuraminidase (NA) for prevention and treatment of influenza. Here, we combine the strengths of anti-influenza antibodies and small molecules by site-specific conjugation of the NA inhibitor zanamivir to MEDI8852, an HA-specific fully human monoclonal antibody. MEDI8852 targets the conserved stem region of HA and inhibits HA-mediated fusion of the viral and host cell membranes. Elimination of virus-infected cells involves Fcγ receptor–mediated effector functions. The efficacy of MEDI8852 is limited to influenza A viruses. Zanamivir, on the other hand, binds to the active site of NA in both influenza A and B viruses to inhibit NA activity and virus release. However, because of its small size, zanamivir has a short half-life and requires repeated dosing at high concentrations. We produced a MEDI8852–zanamivir antibody–drug conjugate (ADC) that engages Fc-mediated effector functions and benefits from neonatal Fc receptor (FcRn)-mediated recycling. The MEDI8852–zanamivir conjugate extends the circulatory half-life of zanamivir, targets both influenza HA and NA, and shows enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to MEDI8852 alone. The MEDI8852–zanamivir conjugate protected mice from a lethal (10 × LD50) challenge with influenza A and B viruses at a dose similar to that required for broadly neutralizing anti-NA antibodies, with the added advantage of simultaneously targeting NA (influenza A and B) and HA (influenza A).

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2424889122

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Identification and characterization of a broadly neutralizing and protective #nanobody against the #HA1 domain of #H5 avian #influenza virus #hemagglutinin

ABSTRACT

The highly pathogenic avian influenza viruses (HPAIVs) of subtype H5, particularly those of the currently circulating clades 2.3.2.1 and 2.3.4.4, are largely responsible for the sporadic human infections that frequently present with a high case fatality rate. Consequently, there is an urgent necessity for the development of advanced antiviral therapeutic options against the H5 HPAIVs. Herein, the yeast two-hybrid system was employed for identifying seven nanobodies that bind the HA1 domain of hemagglutinin (HA). Among these nanobodies, Nb10 was found to exhibit high-affinity and broad-spectrum neutralization capacity against viruses of clades 2.3.2.1 and 2.3.4.4 under both in vitro and in vivo conditions. Surprisingly, Nb10 exhibited excellent efficacy against the recombinant viruses Re6/PR8, Re8/PR8, Re10/PR8, Re11/PR8, and Re14/PR8 of the subtype H5, with average half-maximal inhibitory concentrations ranging from 0.01 to 0.42 µg/mL in a microneutralization assay. Furthermore, the intratracheal administration of Nb10 resulted in remarkable prophylactic and therapeutic efficacy in mice. The findings herein reveal that the virus-neutralizing effect of Nb10 is achieved by obstructing viral entrance into host cells. Moreover, Western blot analysis and enzyme-linked immunosorbent assay revealed that Nb10 recognizes a conformational epitope located in the region spanning amino acid residues 50–271 of the protein HA1 displayed on the surface of yeast cells. The predicted structure of the binding pocket indicates that Nb10 recognizes the highly conserved receptor-binding site of HA1. Taken together, the current study offers valuable insights for the development of protective therapeutics with broad-spectrum activity and the design of broadly protective influenza vaccines.

IMPORTANCE

HPAIVs of subtype H5 have raised substantial public health concerns regarding the potential for viral adaptation and sustained human-to-human transmission. The prevention and treatment of the disease are replete with numerous challenges due to frequent antigenic alterations in the virus. Nanobodies have significant potential for clinical applications and therapies owing to their small size and robust tissue-penetrating capabilities. Herein, we describe the identification of Nb10, a broad-spectrum virus-neutralizing and protective nanobody that is effective against the currently circulating H5 HPAIVs of clades 2.3.2.1 and 2.3.4.4. The intratracheal administration of Nb10 afforded significant protection in mice infected with the H5 virus. This result provides novel insights for the rational design of antiviral pharmaceuticals. Furthermore, an analysis of the binding site of the target protein HA1 may be useful for the development of more effective vaccinations against influenza viruses of the subtype H5.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.02090-24?af=R

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#Israel - #Influenza A #H5N8 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 A wild Booted Eagle in HaZafon Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6408

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Integrating Behavioural Science and #Epidemiology to Improve Early #Detection of Zoonotic #Swine #Influenza in the #Netherlands

Abstract

Background and Objectives: 

The Netherlands faces zoonotic disease risks due to its dense human and livestock populations. The 2009 H1N1 outbreak highlighted the pandemic potential of influenza virus reassortment. Effective preparedness requires integrating behavioural and epidemiological models. Human behaviour, shaped by personal, social, and institutional factors, is critical in detecting, intervening, and treating diseases. Using the Theory of Planned Behaviour (TPB), a framework was developed integrating knowledge from the TPB to improve early detection and response, using (zoonotic) swine influenza as a case study. 

Material and Methods: 

Within the framework we defined the desired outcome: timely detection and notification of symptomatic (and hypothetical zoonotic) swine influenza to prevent its spread. Actions, such as symptom recognition and disease reporting, were linked to key drivers extracted from the TPB and disease transmission modelling. Expert elicitation estimated the likelihood of action for different farmer profiles, while disease transmission modelling assessed farm-to-farm spread probabilities. Simulations integrated these probabilities to evaluate intervention effectiveness across different scenarios. 

Results: 

The framework successfully combined behavioural science and epidemiology, offering nuanced estimates of intervention effectiveness. For early detection, 95% of farmers were estimated to notify their veterinarian within 13 days post-infection. Key factors influencing action included symptom recognition and disease spread extent. The farmer profiles influenced response likelihood, while human infections linked to outbreaks had minimal impact. Farm density and assumptions about transmission probabilities significantly affected the likelihood of spread before notification. 

Discussion and Conclusion: 

The framework provides a systematic approach for integrating social and epidemiological insights to support evidence-based policies. The work can be further enhanced by complementing expert judgement with more extensive stakeholder surveys, randomized scenario presentations, and immersive methods. This pragmatic tool aids policymakers in designing targeted interventions for zoonotic disease preparedness.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.03.646521v1?rss=1

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#Landscape of #H5 #Infections in #ASEAN Region: Past Insights, Present Realities, & Future Strategies

Abstract

The H5 Avian Influenza A virus infection has emerged as a global concern, particularly in the ASEAN region. This viral infection poses a significant threat to the poultry industry, public health, and regional economies. This region’s reliance on poultry production and the zoonotic potential of H5 subtypes, with documented transmission to various mammalian species and humans, necessitates proactive mitigation strategies. Over the years, comprehensive efforts such as surveillance, vaccination programs, biosecurity measures, and public health education have been implemented to keep outbreaks at bay. In this review, we provide a thorough overview of the H5 infections in the ASEAN region, focusing on the unique challenges and successes in this geographic area. We analyze epidemiological trends, including specific high-risk populations and transmission patterns, and assess the socioeconomic impact of H5 outbreaks on local communities. We also examine regional responses, highlighting innovative surveillance programs, vaccination strategies, and biosecurity measures implemented to control the virus. Furthermore, we explore the crucial role of the One Health approach, emphasizing interdisciplinary collaboration between human, animal, and environmental health sectors. Finally, we discuss future strategies for prevention and control, including the importance of regional cooperation in combating this evolving threat. Through this, we aim to provide valuable insights to the public, policymakers, and researchers involved in tackling H5 infections globally.

Source: Viruses, https://www.mdpi.com/1999-4915/17/4/535

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Sustained circulation of #enterovirus D68 in #Europe in 2023 and continued #evolution of #EVD68 B3-lineages associated with distinct amino acid substitutions in VP1 protein

Highlights

• Enterovirus D68 (EV-D68) was circulating in Europe in 2023

• Most EV-D68 cases were captured through clinical EV surveillance

• Phylogenetic analysis of the VP1 region revealed a distinct B3-derived lineage

• The identified B3 lineage presented a previously undescribed residue change, D554E

Abstract

Background

Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges. Here, we describe the circulation of EV-D68 in Europe in 2023 and track its genetic evolution.

Study design

Data was compiled from members of the European Non-Polio Network (ENPEN). This included monthly data on the total number of EV samples tested, EV positive samples, EV-D68 positive samples and cases, and other EV positive samples detected in 2023. Information on sample types and surveillance system was recorded. Sequence data from the VP1 gene was used for phylogenetic and amino acid sequence analysis.

Results

EV was detected in 13585 out of 203622 diagnostic samples tested (6.7%), of which 402 (3.0%) were determined as EV-D68, representing 386 cases. EV-D68 infections peaked in October 2023 (136/386; 35.2%). 267/386 (69.2%) of EV-D68 cases were captured through clinical EV surveillance, almost all of which (202/204 of positive samples with sample type information) were detected in respiratory specimens. Phylogenetic analysis performed on 99 VP1 sequences revealed a distinct B3-derived lineage with a previously undescribed residue change, D554E, in Europe.

Conclusions

The study documents sustained circulation of EV-D68 in Europe in 2023, the evolution of B3-derived lineages, and appearance of previously undescribed amino acid substitutions in Europe. This stresses the need for continuous EV-D68 surveillance and harmonization of EV-D68 detection practices towards better data comparability across countries.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000277?dgcid=rss_sd_all

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Judith, Giorgione (1504)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/giorgione/judith

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Development of an Intranasally- and Intramuscularly-Administrable #Replicon #Vaccine Efficacious Against #H5N1 #Influenza Virus

Abstract

The risk of a respiratory viral pandemic is significant, including from the now widespread panzootic H5N1 influenza virus, highlighting the need for effective, stable, and inexpensive vaccine technologies that elicit strongly protective immunity. Intranasal vaccines can stimulate local immune responses at the site of natural respiratory viral infection, a key characteristic that can not only reduce morbidity and mortality caused by respiratory viruses but also potentially reduce viral transmissibility to limit outbreaks. Nucleic acid vaccines are now a valuable tool in pandemic responses, with high potency and rapid adaptability to target circulating or emerging viral strains; however, data are limited on which vaccine attributes are needed for efficient transmucosal delivery and immune stimulation following intranasal delivery. To demonstrate proof of concept, here we have developed a replicon vaccine expressing an H5 influenza antigen that uses a nanostructured lipid carrier (NLC) delivery system. A relationship was established between the molar ratio of positive charges on the NLC to the negative charges on the nucleic acid (N:P ratio) and the immunogenicity of the vaccine formulations, with higher N:P ratios resulting in an increase in vaccine immunogenicity. We demonstrated the ability of this replicon vaccine to be administered via intramuscular and intranasal routes with a singular vaccine formulation. The vaccine induced systemic immunity when dosed intramuscularly or intranasally in an immunocompetent mouse model, whereas intranasal dosing uniquely stimulated a strong mucosal immune response. Moreover, a mixed intramuscular/intranasal dosing strategy using this unified formulation stimulated a balanced systemic and mucosal immune response. Finally, we demonstrated the protective efficacy of this intranasally and intramuscularly/intranasally delivered H5 replicon-NLC vaccine against morbidity and mortality in a lethal H5N1 influenza challenge ferret model. This work establishes the replicon-NLC vaccine platform as a potential novel intranasal technology for rapid pandemic response.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.31.646478v1

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Impact of inactivated #vaccine on #transmission and #evolution of #H9N2 avian #influenza virus in #chickens

Abstract

H9N2 avian influenza virus (AIV) is endemic in poultry worldwide and increasingly zoonotic. Despite the long-term widespread use of inactivated vaccines, H9N2 AIVs remain dominant in chicken flocks. We demonstrated that inactivated vaccines did not prevent the replication of H9N2 AIVs in the upper airway of vaccinated chickens. Viral transmission was enhanced during sequential passage in vaccinated chickens, which was attributed to the restricted production of defective interfering particles and the introduction of stable mutations (NP-N417D, M1-V219I, and NS1-R140W) which enhanced viral replication. Notably, the genetic diversity of H9N2 AIVs was greater and included more potential mammal/human-adapted mutations after passage through vaccinated chickens than through naïve chickens, which might facilitate the emergence of mammal-adapted strains. By contrast, vaccines inducing cellular/mucosal immunity in the upper respiratory tract effectively limit H9N2 AIV. These findings highlight the limitations of inactivated vaccines and the need for revised vaccination strategies to control H9N2 AIV.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01115-y

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Ann Intern Med

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2. PANG Y, Li H, Chen X, Cao Y, et al
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   PubMed         Abstract available
   
   

   
   Biochemistry

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6. JAFARI N, Akbari H, Maghsoodi A, Sarbakhsh P, et al
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#Mexico: The Ministry of #Health reports the #detection of the first #human case of avian #influenza A (#H5N1)

{Auto translated}

www.gob.mx/salud

The Ministry of Health reports the detection of the first human case of avian influenza A (H5N1) in Mexico. 

The case occurred in a three-year-old girl residing in the state of Durango. On April 1, the Institute of Epidemiological Diagnosis and Reference (InDRE) confirmed the result of influenza A (H5N1). The patient initially received treatment with oseltamivir and is currently hospitalized in a tertiary care unit in the city of Torreón, where her condition is reported to be serious. 

Once the case was confirmed, the following actions were immediately implemented: 

-- Notification to the World Health Organization, in accordance with the protocol established for this purpose in the International Health Regulations. 

Health

-- Health personnel from the Durango and Coahuila Health Services were trained in relation to the National Guide for the preparation, prevention and response to a zoonotic influenza outbreak or event at the animal-human interface. 

-- Intentional search operations were initiated for cases suspected of viral respiratory illness. 

Semarnat - Conanp

-- Biological surveys and sampling of wild and synanthropic birds were carried out in the area of ​​influence surrounding the home of the positive case of avian influenza A (H5N1), and a permanent monitoring system was established for the timely detection of other similar cases in wildlife living in the area.

Agriculture - Senasica

-- The Ministry of Agriculture and Rural Development, through the National Service of Health, Safety, and Agrifood Quality (Senasica), reported that no commercial production units have been affected by avian influenza A (H5N1) in any region of the country. However, Senasica continues its active epidemiological surveillance efforts to promptly identify any potential cases. If so, the corresponding national and international protocols will be implemented.

The Ministry of Health informs the population:

-- The WHO considers the public health risk of this virus to the general population to be low, so eating well-cooked chicken or eggs does not pose a risk to human health. Zoonotic influenza is a disease that can be transmitted from birds or other animals to humans. To date, there is no evidence of sustained human-to-human transmission. 

-- The Ministry of Health has a strategic reserve of 40,000 oseltamivir treatments. 

-- The population is recommended to: 

- Wash your hands frequently with soap and water or 70 percent alcohol-based solutions. 

- Wear a face mask if you have respiratory symptoms and ventilate spaces. 

- Cover your mouth and nose when coughing or sneezing. 

- Wash your hands before handling cooked foods and after handling raw foods. 

- Cook chicken and eggs properly (over 70°C) 

- Do not use the same utensils to handle raw and cooked foods. 

- Avoid touching or approaching wild animals. 

- Do not handle or pick up dead animals. 

- Do not touch sick or dead birds or poultry due to unknown causes. 

- Wear gloves, face masks, and protective clothing if you work on farms or slaughterhouses and have contact with birds or other animals, their products, and waste. 

-- Monitor for signs of illness or abnormal death in farm or backyard animals and report them immediately to the authorities. 

- The Ministry of Health recommends seeking medical attention if you experience fever, conjunctivitis (burning, itching, redness of the eyes), cough, sore throat, runny nose, difficulty breathing, headache, vomiting, diarrhea, bleeding, or altered consciousness after contact with sick or dead birds or other animals. 

Source: Ministry of Health, https://www.gob.mx/salud/prensa/secretaria-de-salud-informa-la-deteccion-del-primer-caso-humano-de-influenza-aviar-a-h5n1

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Synergistic effects of PA (S184N) and #PB2 (E627K) #mutations on the increased pathogenicity of #H3N2 canine #influenza virus #infections in mice and #dogs

ABSTRACT

As companion animals, dogs are susceptible to various subtypes of influenza A virus (IAV), with the H3N2 and H3N8 subtypes of canine influenza virus (CIV) stably circulating among canines. Compared to the H3N8 CIV, the H3N2 CIV is more widely prevalent in canine populations and demonstrates increased adaptability to mammals, potentially facilitating cross-species transmission. Therefore, a comprehensive elucidation of the mechanisms underlying H3N2 CIV adaptation to mammals is imperative. In this study, we serially passaged the GD14-WT strain in murine lungs, successfully establishing a lethal H3N2 CIV infection model. From this model, we isolated the lethal strain GD14-MA and identified the key lethal mutations PA(S184N) and PB2(E627K). Moreover, the GD14-ma[PA(S184N)+PB2(E627K)] strain exhibited markedly enhanced pathogenicity in dogs. Viral titers in lung tissues from infected dogs and mice showed that GD14-ma[PA(S184N)+PB2(E627K)] does not increase its pathogenicity to mice and dogs by upregulating viral titers compared to the GD14-WT strain. Notably, sequence alignments across all H3N2 IAVs showed an increasing prevalence of the PA (S184N) and PB2 (E627K) mutations from avian to human hosts. Finally, single-cell RNA sequencing of infected mouse lung tissues showed that GD14-ma[PA(S184N)+PB2(E627K)] effectively evaded host antiviral responses, inducing a robust inflammatory reaction. Considering the recognized role of the PB2 (E627K) mutation in the mammalian adaptation of IAVs, our findings underscore the importance of ongoing surveillance for the PA (S184N) mutation in H3N2 IAVs.

IMPORTANCE

Since the 21st century, zoonotic viruses have frequently crossed species barriers, posing significant global public health challenges. Dogs are susceptible to various influenza A viruses (IAVs), particularly the H3N2 canine influenza virus (CIV), which has stably circulated and evolved to enhance its adaptability to mammals, including an increased affinity for the human-like SAα2,6-Gal receptor, posing a potential public health threat. Here, we simulated H3N2 CIV adaptation in mice, revealed that the synergistic PA(S184N) and PB2(E627K) mutations augment H3N2 CIV pathogenicity in dogs and mice, and elucidated the underlying mechanisms at the single-cell level. Our study provides molecular evidence for adapting the H3N2 CIV to mammals and underscores the importance of vigilant monitoring of genetic variations in H3N2 CIV.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01984-24?af=R

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {as of April 4 '25}

 

{Excerpt}

Time Period: March 23, 2025 - March 29, 2025

-- H5 Detection: 9 sites (2.2%)

-- No Detection: 400 sites (97.8%)

-- No samples in last week: 228 sites

(...)

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

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#UK {#England} - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

{England} Backyard flock of 40 chickens. Increased mortality and other clinical signs were reported. Samples tested positive for HPAI H5N1.

Source: WOAH, https://wahis.woah.org/#/in-review/6401

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#Nirmatrelvir–ritonavir versus placebo–ritonavir in individuals with #longCOVID in the #USA (PAX LC): a double-blind, randomised, placebo-controlled, phase 2, decentralised trial

Summary

Background

The substantial burden of post-COVID-19 condition (also known as long COVID) underscores the need for effective pharmacological interventions. Given that viral persistence has been hypothesised as a potential cause of long COVID, antiviral therapy might offer a promising approach to alleviating long COVID symptoms. We therefore investigated the efficacy, safety, and tolerability of nirmatrelvir–ritonavir for treating long COVID.

Methods

In this phase 2, decentralised, double-blind, randomised controlled trial, adults (aged ≥18 years) from the 48 states across the contiguous USA, with previous documented SARS-CoV-2 infection and long COVID symptoms starting within 4 weeks of initial infection and persisting for at least 12 weeks, were eligible for inclusion. Key exclusion criteria were use of nirmatrelvir–ritonavir within the previous 2 months, CYP3A4-dependent medications, or strong CYP3A4 inducers; acute medical illness such as SARS-CoV-2 infection within the past 2 weeks; active liver disease; renal impairment; and immunocompromise. Using software for 1:1 stratified block random assignment, participants were randomly allocated to receive either two tablets of nirmatrelvir (150 mg each) and one tablet of ritonavir (100 mg), or placebo and one tablet of ritonavir (100 mg), orally administered twice daily for 15 days, stratified by age, sex at birth, and COVID-19 vaccination status. Participants, clinicians, and the study team were masked to treatment allocation. The primary efficacy endpoint was the change in the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score (PHSS) from baseline to day 28, analysed by intention to treat. Safety endpoints were reported from baseline to week 6 in all participants who were exposed to the study treatment. This trial is registered with ClinicalTrials.gov (NCT05668091) and is now closed to new participants.

Findings

Between April 14, 2023, and Feb 26, 2024, 119 participants were screened. 100 were enrolled (66 [66%] female participants and 34 [34%] male participants), with 49 assigned to the nirmatrelvir–ritonavir group and 51 to the placebo–ritonavir group (intention-to-treat population). Three participants in the nirmatrelvir–ritonavir group and two in the placebo–ritonavir group withdrew before starting treatment and were excluded from the safety population. The mean PROMIS-29 PHSS at baseline was 39·6 (95% CI 37·4 to 41·9) in the nirmatrelvir–ritonavir group and 36·3 (34·4 to 38·2) in the placebo–ritonavir group. The adjusted change from baseline to day 28 was 0·45 (–0·93 to 1·83) in the nirmatrelvir–ritonavir group and 1·01 (–0·30 to 2·31) in the placebo–ritonavir group (adjusted mean difference –0·55 [95% CI –2·32 to 1·21; p=0·54]). No deaths or serious adverse events were recorded between baseline and week 6. Study drug-related treatment-emergent adverse events were reported in more participants in the nirmatrelvir–ritonavir group (35 [76%] of 46) compared with the placebo–ritonavir group (27 [55%] of 49), mostly driven by dysgeusia. Early treatment termination due to an adverse event occurred in two participants in the nirmatrelvir–ritonavir group and one in the placebo–ritonavir group.

Interpretation

Nirmatrelvir–ritonavir administered for 15 days did not significantly improve health outcomes in participants with long COVID compared with placebo–ritonavir at day 28. However, the study showed the feasibility of large-scale, decentralised trials in long COVID.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00073-8/fulltext?rss=yes

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#Influenza #H1N1pdm09 Virus with Reduced Susceptibility to #Baloxavir, #Japan, 2024

Abstract

Influenza A(H1N1)pdm09 virus carrying an I38N substitution was detected in an untreated teenager in Japan. The I38N mutant virus exhibited reduced susceptibility to baloxavir but remained susceptible to neuraminidase inhibitors and showed reduced growth capability. Monitoring antiviral drug susceptibility of influenza viruses is necessary to aid public health planning and clinical recommendations.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1123_article

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