Thursday, July 17, 2025

#Antiviral #therapy for #HPAI and reported #oseltamivir #resistance in #Canada

{Excerpt}

Highly pathogenic avian influenza (HPAI) A(H5Nx) clade 2.3.4.4b viruses have been circulating in North America since late 2021. Since their initial incursion, they have been associated with unprecedented mortality in wild birds, domestic poultry, and marine mammals throughout the Americas, and are now seen across all global regions except Oceania. Furthermore, transmission among dairy cattle and poultry in the United States has led to growing numbers of human cases, and there was a severe human case in Canada with no known infected animal exposure (1,2).

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Source: Journal of the Association of Medical Microbiology and Infectious Disease Canada, https://utppublishing.com/doi/10.3138/jammi-2025-0307

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#Clinical features of a #fatal case of acute #encephalitis associated with a novel influenza #H3N2 #recombinant virus possessing human-origin #H7N9 internal genes: a descriptive study

ABSTRACT

Newly emerging or “re-emerging” influenza viruses have been regarded as a huge global threat to human public health. However, there are few reports of human deaths caused by newly emerging influenza viruses derived from pigs and poultry. Here, we described the clinical and virological features of a fatal encephalitis caused by a novel H3N2 reassortant virus generated from swine H3N2 and human H7N9 viruses. A 7-year-old boy was diagnosed with acute encephalitis in Yixing, China, in August 2022. Chest computed tomography (CT) showed mild pneumonia. Brain CT indicated acute encephalitis companied brain parenchyma swelling. Haematological examinations revealed a markedly elevation of lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase and cytokines. Pathogenic analysis confirmed that a novel H3N2 virus (A/Yixing/805/2022, YX805) was responsible for this case. Phylogenetic analysis showed that the surface protein-coding genes were originated from swine-origin H3N2 viruses, whereas the internal protein-coding genes were derived from human-origin H7N9 viruses. This virus triggers stronger cytokines storm than these genetically related H7N9 viruses and has a natural resistance to neuraminidase inhibitors. The YX805 virus is highly pathogenic to mice. Our study highlights the urgent need to enhance epidemiological surveys for reassortment events between swine and avian influenza virus by full genome sequencing.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2528536

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#Argentina - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification



The Official Veterinary Services received a notification concerning bird mortality and signs consistent with high pathogenicity avian influenza (HPAI) in a backyard in the Buenos Aires province. On the same day, the suspicion was addressed and samples were taken for analysis. The samples were analysed by the Official Laboratory and came back positive for HPAI H5 clade 2.3.4.4. The affected premises are adjacent to bodies of water, so contact with wild birds is presumed

On 14/07/2025, the Official Veterinary Services received a notification concerning bird mortality and signs consistent with high pathogenicity avian influenza (HPAI) in a backyard in the town of Lezama, in the Buenos Aires province. On the same day, the suspicion was addressed and samples were taken for analysis. On 15/07/2025 the samples were analysed by the Official Laboratory and came back positive for HPAI H5 clade 2.3.4.4. The species involved are chickens, peacocks, pheasants and guinea fowl. The affected premises are adjacent to bodies of water, so contact with wild birds is presumed. Stamping out and disposal of all the birds will be carried out, as well as cleaning and disinfection of the premises. We will update the population information in subsequent follow-up reports.

Source: WOAH, https://wahis.woah.org/#/in-review/6630

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#Henipavirus in Northern Short-Tailed #Shrew, #Alabama, #USA

{Excerpt}

To the Editor: The article “Henipavirus in northern short-tailed shrew, Alabama, USA,” (1), describing the discovery of Camp Hill virus (family Paramyxoviridae) in the northern short-tailed shrew (Blarina brevicauda), sparked major media attention and raised concerns about zoonotic transmission and potential pandemic risk. However, it would be advisable to reevaluate this virus discovery within the broader context of related viruses. The increase in identified henipa-like viruses in various shrew species (2–4) led the International Committee on Taxonomy of Viruses to classify these henipa-like viruses into a distinct genus, Parahenipavirus (5), acknowledging their genetic difference from the highly pathogenic Hendra and Nipah virus.

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Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0401_article

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#Nipah Virus #Antibodies in #Bats, the #Philippines, 2013–2022

Abstract

In 2014, an outbreak of zoonotic Nipah virus (NiV) occurred on Mindanao Island, the Philippines. We investigated the prevalence of NiV in Philippine bats. Because neutralizing antibodies were detected in insectivorous bats on Siargao Island, public health officials should consider that the distribution range of NiV is not limited to Mindanao Island.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0210_article

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Isolation of Highly Pathogenic Avian #Influenza #H5N1 Virus from #Cat #Urine after Raw #Milk Ingestion, #USA

Abstract

In 2024, 3 domestic cats in California, USA consumed raw milk contaminated with highly pathogenic avian influenza A(H5N1) virus. Fever and neurologic signs developed; 2 cats died. The surviving cat’s urine tested positive for H5N1 virus by reverse transcription PCR. Raw dairy products pose a risk to both animal and human health.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0309_article

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Community-Scale Surveillance of #SARS-CoV-2 and #Influenza A Viruses in Wild #Mammals, #USA, 2022–2023

Abstract

Sampling of mammal communities across the United States during 2022–2023 detected evidence of SARS-CoV-2 antibodies in 3 new species and 2 previously described species and evidence of influenza A antibodies in 2 previously described species. Our analysis provides surveillance and sampling guidance for detection of rare exposure events.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/24-1671_article

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Multidisciplinary #Tracking of Highly Pathogenic Avian #Influenza #H5N1 #Outbreak in Griffon #Vultures, Southern #Europe, 2022

Abstract

Since 2021, highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus has affected wild bird populations globally. Griffon vultures (Gyps fulvus), a species hitherto considered unexposed, experienced an HPAI H5N1 outbreak in 2022 in southern Europe, leading to moderate mortality and reduced breeding success. The integration of virological, serologic, phylogenetic, and ecologic data revealed a short yet intense viral circulation and a probable common source of infection. The dissemination across Spain and France was likely caused by frequent interpopulation movements of birds. This integrated overview of the 2022 HPAI outbreak in vultures provides novel insights into the role of large-scale movements of wild birds in the spread of such disease. Understanding the epidemiologic dynamics of HPAI H5N1 in these scavenger species is crucial because the birds play vital roles in ecosystem functioning. Their susceptibility to this virus highlights potential broader ecologic effects of the ongoing outbreaks.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/24-1456_article

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Laboratory #Diagnosis of #Hendra and #Nipah: Two Emerging Zoonotic Diseases with One Health Significance

Abstract

Hendra virus (HeV) and Nipah virus (NiV) are two highly pathogenic RNA viruses with zoonotic potential, which can cause severe diseases with high mortality rates (50–100%) in humans and animals. Given this context, these viruses are classified as Biosafety Level 4 (BSL-4) pathogens, thus limiting research studies. Despite the high case fatalities, there are currently no human vaccines available for either virus, owing in part to the limitations in research and hesitancy in funding. In the absence of widespread vaccination, diagnostic tests are crucial for the rapid identification of cases and disease surveillance. This review synthesizes current knowledge on the epidemiology, transmission dynamics, and pathogenesis of NiV and HeV to contextualize a detailed assessment of the available diagnostic tools. We examined molecular and serological assays, including RT-PCR, ELISA, and LAMP, highlighting sample sources, detection windows, and performance. Diagnostic considerations across human and animal hosts are discussed, with emphasis on outbreak applicability and field-readiness, given the need for diagnostic assays that are suitable for use in low-income areas. Further development of diagnostic assays, including isothermal amplification tests and other next-generation approaches, is recommended to fill the gap in rapid, point-of-care diagnostics.

Source: Viruses, https://www.mdpi.com/1999-4915/17/7/1003

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Anthropozoonotic #spillovers reveal sustained long-term cryptic #circulation of #SARS-CoV-2 within and between #Lithuanian #mink farms

Abstract

Several studies have documented reverse zoonotic transmission of SARS-CoV-2, including in farmed mink which are susceptible to human respiratory viruses and are known for serving as a reservoir capable of generating new virus variants in densely populated farms. Here, we present the results of a genomic investigation launched in response to detected human infections with mink-origin SARS-CoV-2 lineages, and show evidence of at least 14 high-confidence introductions of SARS-CoV-2 from humans into farmed mink in Lithuania where sustained transmission in farmed mink lasted up to a year. We estimated the most likely timeframes for these introductions encompassing at least six SARS-CoV-2 lineages, some of which were already extinct in humans, with Bayesian phylogenetic and molecular clock analyses. This study highlights the public health risks posed by fur farms and underscores that passive genomic surveillance systems are ineffective without the active involvement and expertise of responsible institutions.


Competing Interest Statement

The authors have declared no competing interest.


Funding Statement

Gytis Dudas was supported by EMBO installation grant EMBO-IG-5305-2023.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.15.25331253v1

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Wednesday, July 16, 2025

Detection of low pre-existing humoral #immunity against #influenza virus #H5N1 clade 2.3.4.4b in unexposed individuals

Abstract

The spill-over of Influenza A virus H5N1 clade 2.3.4.4b from cattle to humans highlights the risk of a human H5N1 pandemic. Given the impact of pre-existing immunity on the course and severity of viral infections, we comprehensively assessed the humoral immunity against the H5N1 A/Texas/37/2024 isolate in H5N1-naive individuals. To this end, we performed complementary binding and neutralization assays on 66 subjects and ranked activities among a panel of 76 influenza A virus isolates. We detected low but distinct cross-neutralizing titers against A/Texas/37/2024 with a 3.9 to 15.6-fold reduction compared to selected H1N1 or H3N2 strains. By cloning and evaluating 136 monoclonal antibodies from memory B cells, we identified potent A/Texas/37/2024-neutralizing monoclonal antibodies in five out of six investigated individuals. These antibodies cross-neutralize H1, compete with antibodies targeting the HA stem, and protect mice from lethal H5N1 challenge. Our findings demonstrate partial pre-existing humoral immunity to A/Texas/37/2024 in H5N1-naive individuals.


Competing Interest Statement

DR, MM, CK, FK, and ML are members of the non-profit Center for Predictive Analysis of Viral Evolution (Previr). LG, HG, CK and FK are inventors on patent applications on virus neutralizing antibodies filed by the University of Cologne and have received payments from the University of Cologne for licensed patents.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.22.634277v2

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Development of #DNA and #mRNA-LNP #vaccines against an #H5N1 clade 2.3.4.4b #influenza virus

ABSTRACT

Effective vaccines are an important public health tool which may be needed to combat the emerging, highly pathogenic H5N1 avian influenza viruses currently circulating in cattle and poultry in the United States. While nucleic acid-based vaccines such as mRNA-lipid nanoparticles (LNPs) have several potential advantages during a viral epidemic compared to traditional seasonal influenza vaccines, their utility and efficacy against H5N1 viruses remain incompletely defined. Here, we developed novel DNA- and mRNA-LNP-based vaccines encoding both hemagglutinin (HA) and neuraminidase (NA) proteins from the human-isolated highly pathogenic avian influenza H5N1 strain, A/Texas/37/2024, in a single open reading frame. This dual-antigen expression approach elicited strong protective immune responses targeting both the HA and NA proteins and provided complete protection against lethal viral challenges in a murine model. The pre-clinical data described in this work suggest that these multi-valent, adaptable, and scalable vaccine approaches may represent practical and rapid solutions to mediate robust protection from emerging zoonotic influenza virus threats.


IMPORTANCE

Vaccines capable of protecting from infection with the H5N1 influenza viruses actively circulating in dairy cattle could be deployed to protect livestock and potentially also be used to protect human health. Here, we describe the development of protective DNA and mRNA-lipid nanoparticle vaccines targeting hemagglutinin and neuraminidase proteins from the highly pathogenic avian influenza (HPAI) H5N1 A/Texas/37/2024 virus and show that they are both protective against severe morbidity and mortality in a mouse model. Thus, the vaccines described in this work represent effective approaches to limit the current circulation of H5N1 viruses in animals and may represent practical solutions for human vaccination in the event of sustained human transmission of HPAI H5N1 viruses.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00795-25?af=R

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Low levels of #H5N1 HA and NA #antibodies in the #human population are boosted by seasonal #H1N1 #infection but not by #H3N2 infection or influenza #vaccination

Abstract

An increase in the number of human cases of influenza A/H5N1 infection in the US has raised concerns about the pandemic potential of the virus. Preexisting population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody responses were detected in a cohort of 73 individuals. Conversely, bovine A/H5N1 NA binding and neuraminidase-inhibiting antibody responses were comparable to those against a human A/H1N1 NA at baseline. Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1 neutralizing antibody, as well as increases in NA-binding and NA-inhibiting antibodies to bovine A/H5N1 NA. While the degree of protection afforded by these A/H5N1 cross-reactive antibodies is not known, incorporating NA or enhancing current seasonal vaccine formulations to increase NA-specific antibody responses may increase antibody breadth and protection against both seasonal and pandemic influenza viruses.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.13.664638v1

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

 



By Scott Wieman - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=24620634


A wild Herring Gull in Nordland Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6621

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#Russia - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification


Di dierat-stock - Crow-1, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=33155653


A wild Carrion Crow in Khabarovsk Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6622

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The #impact of highly pathogenic avian #influenza #H5N1 virus infection on dairy #cows

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 virus has been associated with severe mastitis in dairy cows, leading to decreased milk production. Here we investigated the impact of H5N1 virus infection in health and production parameters in an affected dairy herd in Ohio. Clinical disease, which lasted for about three weeks, was recorded in 20.0% (777/3876) of the adult cows. Milk losses of ~900 kg per cow were recorded in affected cows during a 60 day-post-outbreak period. Seroprevalence was 89.4% (570/637) in the herd, with 76.1% (485/637) of seropositive animals being subclinically infected. Clinically affected cows presented an increased risk of death (6 times) and of premature herd removal (3.6 times) when compared to non-clinical cows. Economic losses due to decreased milk production, mortality, and early herd removal were estimated at $950 per clinically affected cow for a total cost of ~$737,500 for the herd during the observation period. Our results demonstrate a production impact lasting at least 60 days post-clinical diagnosis and major financial consequences of HPAI H5N1 virus infection to dairy farms.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61553-z

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#Surveillance and follow up #outcomes of #myocarditis after #mRNA #COVID19 #vaccination in #Australia

Abstract

Clinical progression and medium-long term morbidity from myocarditis following mRNA COVID-19 vaccinations remains an important but undefined public health concern. We conducted prospective follow-up of individuals with either confirmed or probable myocarditis following monovalent Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccination between 21 April 2021 and 5 July 2022 in Australia. Of 256 individuals who consented to follow up, mostly males following a second dose, 60% (133/221) had ongoing symptoms at 3-6 months and 35% (81/231) at 12-18 months. Self-reported ongoing exercise restrictions, medication requirements, and hospital re-presentations were associated with ongoing symptoms, as was a lower self-reported health status and quality of life. Clinical severity remained mild, with low hospitalisation rates and no deaths in the follow-up period and health-related quality of life improved over time. These findings support ongoing use of mRNA COVID-19 vaccines in at-risk individuals to prevent disease caused by SARS-CoV-2 infection.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01206-w

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Tuesday, July 15, 2025

Emergence of #Parechovirus-A5 #CNS #infections in #children from #Kansas City, #Missouri, #USA

HIGHLIGHTS

• PeV-A5 was the predominant PeV-A genotype detected from CSF/blood in 2024 at CM-KC.

• CM-KC PeV-A5 sequences resemble PeV-A5 sequences reported in Sapporo City, Japan, in 2018.

• The highest number of PeV-A5 detections within a single year in the USA.


ABSTRACT

Background

Parechovirus-A5 (PeV-A5) blood and central nervous system (CNS) infections are rare in the United States of America (USA) and globally. We report an emergence of PeV-A5 infections among infants in Kansas City, Missouri, in 2024.

Methods

Cerebrospinal fluid (CSF) and blood samples from infants were tested for Parechovirus (PeV-A) in 2024 as a part of standard of care at Children's Mercy Kansas City (CM-KC). PeV-A testing included a two-step reverse transcriptase-polymerase chain reaction, and genotyping was conducted using Sanger sequencing. We analyzed the amino acid sequences and phylogeny of the 2024 PeV-A viruses and described the clinical characteristics of PeV-A infected infants.

Results

Among 211 CSF and 46 blood samples from 248 patients, 10 (4%) PeV-A infected patients were detected (8 CSF, 2 blood). Genotyping was successful for viruses from 9 PeV-A infected patients, with 8 identified as PeV-A5 (6 CSF, 2 blood) and 1 as PeV-A4 (CSF). PeV-A5 viral sequences from CM-KC clustered with other known PeV-A5 sequences, being most similar (>97%) to a PeV-A5 viral sequence from Sapporo City, Japan, in 2018. PeV-A5 detections from CM-KC occurred with a summer-fall seasonality. All 8 PeV-A5 infected patients had symptoms of rash with less irritability and lower maximum temperature when compared to previous PeV-A3 and PeV-A4 infected patients at CM-KC.

Conclusions

PeV-A5 emerged as the predominant PeV-A genotype detected from sterile sites (CSF, blood) in infants in Kansas City, Missouri in 2024, representing the highest number of PeV-A5 systemic illness in infants in the USA within a year.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000770?dgcid=rss_sd_all

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Co-circulation of distinct high pathogenicity avian #influenza virus #subtypes in a mass #mortality event in wild #seabirds and co-location with dead #seals

Abstract

H5Nx clade 2.3.4.4b high pathogenicity avian influenza viruses (HPAIV) have been detected repeatedly in Great Britain (GB) since autumn 2020, with H5N1 dominating detections but with low level detection of H5N5 during 2025. Globally, these viruses have caused mass mortalities in captive and wild avian and mammalian populations, including terrestrial and marine mammals. H5N1 has been the dominant subtype, and whilst incursions have overlapped temporally, occurrences have often been spatially distinct. Here, we report the detection of a mortality event in wild birds on the Norfolk coastline in the east of England, where H5N1 HPAIV was detected in five Great Black-backed Gulls (Larus marinus) and a Northern Fulmar (Fulmarus glacialis). Interestingly, at the same site, and as part of the same mortality event, a total of 17 Great Black-backed Gulls, one Herring Gull (Larus argentatus), one Atlantic Puffin (Fratercula arctica) and one Northern Fulmar tested positive for H5N5 HPAIV. Additionally, H5N5 was also detected in 17 co-located Grey Seal carcases (Halichoerus grypus). The H5N1 HPAIV from an infected bird belonged to genotype DI.2, closely related to contemporaneous detections in GB wild birds and poultry. In contrast, all H5N5 HPAIVs from birds and seals were genotype I with a 22-amino acid stalk deletion in NA and the 627K polymorphism in PB2. This represents the first recorded instance in GB of two subtypes being detected within the same avian population at the same location. It is also the first mass detection of HPAIV H5N5 in mammals within GB. Potential infection mechanisms are discussed.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.11.664278v1

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Extended #nirmatrelvir–ritonavir #treatment durations for immunocompromised #patients with #COVID19 (EPIC-IC): a placebo-controlled, randomised, double-blind, phase 2 trial

Summary

Background

Nirmatrelvir–ritonavir is approved for adults with mild-to-moderate COVID-19 who are at risk of severe disease. There are little clinical data to guide the duration of therapy in patients who are immunocompromised. We aimed to compare the approved 5-day regimen of nirmatrelvir–ritonavir with 10-day and 15-day regimens.

Methods

This placebo-controlled, randomised, double-blind, phase 2 trial enrolled non-hospitalised, immunocompromised individuals aged 12 years or older with symptomatic COVID-19 from 73 sites across nine countries. Participants were randomly assigned (1:1:1) to receive 300 mg nirmatrelvir and 100 mg ritonavir orally twice per day for 5, 10, or 15 days. Randomisation was stratified according to whether participants were considered immunocompromised due to use of corticosteroids or tumour necrosis factor blockers. Investigators, participants, and caregivers were masked to the assigned study group. The primary endpoint was proportion of randomly assigned and dosed participants with sustained nasopharyngeal SARS-CoV-2 RNA concentrations below the lower limit of quantification (2·0 log10 copies per mL) from days 15 to 44. Secondary endpoints included the incidence of viral rebound after the end of treatment up to day 44. Safety, a secondary endpoint, was assessed in all randomly assigned participants who received at least one dose of nirmatrelvir–ritonavir. This trial was registered with ClinicalTrials.gov (NCT05438602) and is completed.

Findings

Among 156 participants (84 female, 72 male) randomly assigned from Aug 3, 2022 to July 17, 2023, 150 comprised the analysis population. The primary endpoint was reached in 32 (61·5%, 95% CI 48·3–74·8) of 52 participants in the 5-day treatment group, 34 (70·8%, 58·0–83·7) of 48 participants in the 10-day treatment group, and 33 (66·0%, 52·9–79·1) of 50 participants in the 15-day treatment group. Viral rebound occurred in 17·3% (95% CI 8·2–30·3) of participants in the 5-day group, 2·1% (0·1–11·1) in the 10-day group, and 2·0% (0·1–10·6) in the 15-day group. Adverse events occurred in 28 (52·8%) of 53, 34 (66·7%) of 51, and 31 (60·8%) of 51 participants across the 5-day, 10-day, and 15-day groups, respectively. Two COVID-19-related hospitalisations were reported, both in the 5-day treatment group.

Interpretation

No difference was observed between the three treatment durations in the primary endpoint. Extending nirmatrelvir–ritonavir treatment beyond 5 days resulted in a nominal improvement in the frequency of viral rebound and was generally well tolerated.

Funding

Pfizer.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00221-X/fulltext?rss=yes

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