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Modeling suggests #SARS-CoV-2 #rebound after #nirmatrelvir-ritonavir #treatment is driven by target cell preservation coupled with incomplete viral clearance

ABSTRACT In a subset of SARS-CoV-2-infected individuals treated with the antiviral nirmatrelvir -ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded. Target cell preservation , either by a robust innate immune response or initiation of N-R near the time of symptom onset, coupled with incomplete viral clearance , appears to be the main factor leading to viral rebound. Moreover, the occurrence of viral rebound is likely influenced by the time of treatment initiation relative to the progression of the infection, with earlier treatments leading to a higher chance of rebound . A comparison with an untreated cohort suggests that early treatments with nirmatrelvir-ritonavir may be associated with a delay in the onset of an adaptive immune response . Nevertheless, our model demonstra...

Highly pathogenic avian #influenza virus (#H5N5) detected in an Atlantic #walrus (Odobenus rosmarus rosmarus) in the #Svalbard Archipelago, #Norway, 2023

ABSTRACT We present the first documented case of highly pathogenic avian influenza virus (HPAIV) subtype H5N5 in an Atlantic walrus (Odobenus rosmarus rosmarus). The animal was found dead in Svalbard , Norway, in 2023. Sequence analysis revealed the highest genetic similarity with virus isolates from different avian hosts. Source: Emerging Microbes and Infections,  https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2456146 _____

Groundbreaking #Ebola #vaccination #trial launches today in #Uganda

{Excerpt} In a global first, Uganda’s Ministry of Health, the World Health Organization (WHO) and other partners today launched a first ever vaccine trial for Ebola from the Sudan species of the virus, and at an unprecedented speed for a randomized vaccine trial in an emergency . The principal investigators from Makerere University and the Uganda Virus Research Institute (UVRI), with support from WHO and other partners, have worked tirelessly to get the trial ready in 4 days since the outbreak was confirmed on 30 January. It is the first trial to assess the clinical efficacy of a vaccine against Ebola disease due to Sudan virus . The speed was achieved through advanced research preparedness, while ensuring full compliance with national and international regulatory and ethical requirements. The candidate vaccine was donated by IAVI , with financial support from WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), Canada’s International Development Research Centre (IDRC), and...

Development of avian #influenza A(#H5) virus #datasets for #Nextclade enables rapid and accurate clade assignment

Abstract The ongoing panzootic of highly pathogenic avian influenza (HPAI) A(H5) viruses is the largest in history , with unprecedented transmission to multiple mammalian species . Avian influenza A viruses of the H5 subtype circulate globally among birds and are classified into distinct clades based on their hemagglutinin (HA) genetic sequences. Thus, the ability to accurately and rapidly assign clades to newly sequenced isolates is key to surveillance and outbreak response. Co-circulation of endemic, low pathogenic avian influenza (LPAI) A(H5) lineages in North American and European wild birds necessitates the ability to rapidly and accurately distinguish between infections arising from these lineages and epizootic HPAI A(H5) viruses. However, currently available clade assignment tools are limited and often require command line expertise, hindering their utility for public health surveillance labs. To address this gap, we have developed datasets to enable A(H5) clade assignments with...

The Emergence of #Coxsackievirus A16 Subgenotype B1c: A Key Driver of the #HFMD #Epidemic in #Guangdong, #China

Abstract Background :  In 2024, mainland China witnessed a significant upsurge in Hand, Foot, and Mouth Disease (HFMD) cases. Coxsackievirus A16 (CVA16) is one of the primary causative agents of HFMD. Long-term monitoring of theCVA16 infection rate and genotype changes is crucial for the prevention and control of HFMD.  Methods :  A total of 40,673 clinical specimens were collected from suspected HFMD cases in Guangdong province from 2018 to 2024, including rectal swabs (n = 27,954), throat swabs (n = 6791), stool (n = 5923), cerebrospinal fluid (n = 3), and herpes fluid (n = 2). A total of 24,410 samples were detected as EV-positive and further typed by RT-PCR. A total of 872 CVA16-positive samples were isolated and further sequenced to obtain the full-length VP1 sequence. Phylogenetic analysis was performed based on viral protein 1 gene (VP1).  Results :  In the first 25 weeks of 2024 , reported cases of HFMD were 1.36 times higher than the mean rates of 2023 ...

The Madonna of the Pesaro Family, Titian (1519-26)

 Public Domain. Source: WikiArt,  https://www.wikiart.org/en/titian/pesaros-madonna-1526 _____

Distal #protein-protein #interactions contribute to #nirmatrelvir #resistance

Abstract SARS-CoV-2 main protease, Mpro , is responsible for processing the viral polyproteins into individual proteins, including the protease itself. Mpro is a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component of Paxlovid). Resistance mutants identified clinically and in viral passage assays contain a combination of active site mutations (e.g., E166V, E166A, L167F), which reduce inhibitor binding and enzymatic activity, and non-active site mutations (e.g., P252L, T21I, L50F), which restore the fitness of viral replication. To probe the role of the non-active site mutations in fitness rescue, here we use an Mpro triple mutant (L50F/E166A/L167F) that confers nirmatrelvir drug resistance with a viral fitness level similar to the wild-type. By comparing peptide and full-length Mpro protein as substrates, we demonstrate that the binding of Mpro substrate involves more than residues in the active site. Particularly, L50F and other non-active site mutations...

#Pandemic #preparedness: analyzing national #plans for respiratory #pathogen pandemics in the #Americas region

Abstract Background The International Health Regulations (2005) (IHR), requires that States Parties develop their capacities to detect, assess, and respond to public health threats and report to the World Health Assembly through the States Parties Annual Report (SPAR). The National Pandemic Preparedness and Response Plans (PPRP) contribute to countries capacities however there are some discrepancies between both tools. To identify gaps and define priority actions to strengthen pandemic plans, we assessed the concordance between national pandemic preparedness and response plans for respiratory pathogens against the pandemic checklist published in 2023 and the SPAR. Methods In this retrospective, semi-quantitative study , conducted in August 2024, we reviewed the most recent respiratory pandemic plans for 35 PAHO member states and assessed their concordance with (1) actionable guidelines in the World Health Organization pandemic checklist and (2) IHR (2005) core capacities using the late...

Structurally convergent #antibodies derived from different #vaccine #strategies target the #influenza virus HA anchor epitope with a subset of VH3 and VK3 genes

Abstract H1N1 influenza viruses are responsible for both seasonal and pandemic influenza . The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their VH and VK genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against...

#Sudan virus disease - #Uganda

Situation at a glance On 30 January 2025, the Ministry of Health of Uganda declared an outbreak of Sudan virus disease (SVD) following confirmation from three national reference laboratories.  The case presented with signs and symptoms between 20 and 21 January and died on 29 January at the National Referral Hospital in Kampala.  As of 30 January 2025, 45 contacts have been identified , including 34 healthcare workers and 11 family members.  Sudan virus disease belongs to the same family as Ebola virus disease. It is caused by Sudan virus (SUDV). It is a severe disease with high case fatality from 41% to 70% in past outbreaks.  In the absence of licensed vaccines and therapeutics for the prevention and treatment of SVD, the risk of potential serious public health impact is high.  Early supportive patient care and treatment may increase the chance of survival from severe disease. Description of the situation On 30 January 2025, the Ministry of Health of Uganda de...

#Coronavirus Disease Research #References (by AMEDEO, February 1 '25)

  Antiviral Res WU Q, Wu H, Hu Y, Zheng X, et al Immune evasion of Omicron variants JN.1, KP.2, and KP.3 to the polyclonal and monoclonal antibodies from COVID-19 convalescents and vaccine recipients. Antiviral Res. 2025 Jan 24:106092. doi: 10.1016/j.antiviral.2025.106092. PubMed           Abstract available Infect Control Hosp Epidemiol HANKINS RJ, Handke L, Fey PD, Cavalieri RJ, et al Prospective, crossover, comparative study of two methods of chlorhexidine bathing. Infect Control Hosp Epidemiol. 2025 Jan 30:1-6. doi: 10.1017/ice.2024. PubMed           Abstract available PISCHEL L, Aguolu OG, Ahmed N, Campbell MM, et al Social mixing patterns of United States healthcare personnel at a quaternary health center: a prospective observational study. Infect Control Hosp Epidemiol. 2025 Jan 30:1-9. doi: 10.1017/ice.2024. PubMed           Abstract availab...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, February 1 '25)

  Biochemistry (Mosc) KOROLEVA ON, Kuzmina NV, Tolstova AP, Dubrovin EV, et al Effect of C- and N-Terminal Polyhistidine Tags on Aggregation of Influenza A Virus Nuclear Export Protein. Biochemistry (Mosc). 2024;89:2238-2251. PubMed           Abstract available BMC Pediatr ZHANG P, Xin M, Bai Y, Ren X, et al Severe central nervous system injury in 9 children with COVID-19. BMC Pediatr. 2025;25:63. PubMed           Abstract available Epidemiol Infect BEDNARSKA NG, Smith S, Bardsley M, Loveridge P, et al Trends in general practitioner consultations for hand foot and mouth disease in England between 2017 and 2022. Epidemiol Infect. 2025;153:e22. PubMed           Abstract available J Virol KIRKPATRICK ROUBIDOUX E, Meliopoulos V, Livingston B, Brigleb PH, et al Intraductal infection with H5N1 clade 2.3.4.4b influenza virus. J Virol. 2025 Jan 31:e0192724....

Emergence of a novel #reassortant highly pathogenic avian #influenza clade 2.3.4.4b A(#H5N2) Virus, 2024

ABSTRACT Reassortant highly pathogenic avian influenza A(H5N2) clade 2.3.4.4.b viruses were detected from ducks and environmental samples in Egypt , June 2024. Genomic and phylogenetic analyses revealed a novel genotype produced by the reassortment of an A( H5N1 ) clade 2.3.3.4b virus with an A( H9N2 ) G1-like virus. Monitoring the spread of this virus is important. Source: Emerging Microbes and Infections,  https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2455601#abstract _____

No #Evidence of Anti - #influenza #Nucleoprotein #Antibodies in Retail #Milk from Across #Canada (April to July 2024)

Abstract Following reports of HPAI H5N1 infections of dairy cattle in the United States (US) in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies , as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the US has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact. Source: MedRxIV,  https://www.medrxiv.org/content/10.1101/2025.01...

Intraductal #infection with #H5N1 clade 2.3.4.4b #influenza virus

LETTER In March 2024, highly pathogenic avian influenza (HPAI) H5N1 of the clade 2.3.4.4b was detected in dairy cows in Texas and has since been detected in several other U.S. states (1). Virus has been detected within cow’s milk , indicating that the mammary epithelium may support viral replication (2). Virus has also been detected on milking machines , leading to a hypothesis that influenza is spreading through fomites from udder to udder instead of the intranasal route (3, 4). There have been studies using cows to better understand mammary infections; however, the cow model is costly and limited (1, 5). We sought to establish a model for intramammary infections of H5N1 and H1N1 influenza virus in mice . (...) Source: Journal of Virology,  https://journals.asm.org/doi/full/10.1128/jvi.01927-24?af=R _____

Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater, January 19-25 2025

{Excerpt} Time Period: January 19 - January 25, 2025 -- H5 Detection : 33 sites ( 10.1% ) -- No Detection : 295 sites ( 89.9% ) -- No samples in last week : 61 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html _____

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

The laboratory diagnosed type H5 on Thursday, January 23 in one of the sick birds that was sampled in the framework of passive surveillance , on January 24 all birds were culled, on January 29 the laboratory confirmed the detection of Neuraminidase 1 and identification of hemagglutinin genes found in the cleavage site of avian influenza virus type A lineage Goose/Guangdong (Gs/GD) subtype H5, clade 2.3.4.4. highly pathogenic. Out of the 408 backyard birds, one died and two became sick in Chiriquí Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6225 ____