Ann Intern Med MARCUCCI M, Chan MTV, Painter TW, Efremov S, et al Effects of a Hypotension-Avoidance Versus a Hypertension-Avoidance Strategy on Neurocognitive Outcomes After Noncardiac Surgery. Ann Intern Med. 2025 Jun 3. doi: 10.7326/ANNALS-24-02841. PubMed Abstract available GOLDMAN JM, Moyer DV Flying the Plane While Building It: Lessons From the COVID-19 Pandemic. Ann Intern Med. 2025 Jun 3. doi: 10.7326/ANNALS-25-02436. PubMed Antiviral Res MALUNE P, Esposito F, Tramontano E Unveiling SARS-CoV-2's heart: role, structure and inhibition of SARS-CoV-2 RNA-dependent RNA polymerase. Antiviral Res. 2025 Jun 3:106208. doi: 10.1016/j.antiviral.2025.106208. PubMed Abstract available BMJ MURPHY F Covid-19: New variant spreading across Asia is found in UK. BMJ. 2025;389:r1161. PubMed LOOI MK Trump wa...
BMC Pediatr ALRASHED R, Almeshawi I, Alshammari A, Alhamoud W, et al Burden of bronchiolitis post-COVID-19 pandemic in children less than 2 years old in 2021-2024: experience from a tertiary center in Saudi Arabia. BMC Pediatr. 2025;25:453. PubMed Abstract available BIGLARI HN, Ahmadi A, Alidousti K, Pouredalati M, et al Growth in the first two years in children born to mothers infected with COVID-19 during pregnancy: a cohort study. BMC Pediatr. 2025;25:448. PubMed Abstract available CHENG J, Wu Y, Ma H, Tang M, et al C-reactive protein and serum amyloid A protein as complementary biomarkers in differentiating viral and bacterial community-acquired pneumonia in children. BMC Pediatr. 2025;25:445. PubMed Abstract available J Gen Virol CAPELASTEGUI F, Goldhill DH H5N1 2.3.4.4b: a review of mammalian adaptations and risk of pandemic e...
Summary Background Onradivir (ZSP1273) is a potent inhibitor of the PB2 subunit of influenza A virus (IAV) polymerase . Our previous, phase 2 clinical trial showed that a 600 mg regimen of onradivir initiated within 48 h of symptom onset can expedite the recovery of adult patients from acute, uncomplicated influenza. Here, we aimed to evaluate the safety and therapeutic efficacy of onradivir in a larger group with acute, uncomplicated influenza. Methods This randomised, double-blind, multicentre, placebo-controlled and oseltamivir-controlled, phase 3 trial was conducted at 68 clinical sites in China . Eligible participants were adults (aged 18–64 years) with an influenza-like illness who screened positive by rapid IAV antigen testing at the first clinical visit, and had a fever (axillary temperature ≥38·0°C) with at least one moderate systemic and one moderate respiratory symptom within 48 h of symptom onset. Patients were randomly assigned into three treatment groups, stratified by in...
{Excerpt} After the spread of SARS-CoV-2 JN.1, its subvariants, such as KP.3 (JN.1.11.1.3)1 and KP.3.1.1 (JN.1.11.1.3.1.1),2 and XEC (a recombinant lineage of two JN.1 subvariants),3 emerged and rapidly spread globally. Subsequently, LP.8.1 (JN.1.11.1.1.1.3.8.1),4 a descendant lineage of KP.1.1.3 (JN.1.11.1.1.1.3), accounts for approximately 30% of all global infections as of April, 2025 , as per data from Nextstrain. Thereafter, NB.1.8.1 (XDV.1.5.1.1.8.1), a descendant lineage of XDV , has started to spread worldwide. XDV is a recombinant lineage of XDE (a recombinant lineage of GW.5.1 [XBB.1.19.1.5.1] and FL.13.4 [XBB.1.9.1.13.4]) and JN.1. NB.1.8.1 has acquired seven spike substitutions and 23 non-spike substitutions compared with JN.1 (appendix pp 15–16). Compared with the XEC spike protein, the NB.1.8.1 spike bears four substitutions : G184S, K478I, A435S, and L1104V (appendix pp 15–16). We estimated the relative effective reproduction number (Re) of NB.1.8.1 using a Bayesian mult...
Abstract Seasonal influenza viruses continue to pose a significant threat, causing substantial morbidity and mortality in the US and worldwide despite the availability of vaccines and antivirals. These challenges may be addressed by improving vaccine immunogenicity through the inclusion of adjuvants that enhance immune responses against key antigens including influenza hemagglutinin (HA). BECC (Bacterial Enzymatic Combinatorial Chemistry) adjuvants are novel Toll-like Receptor 4 (TLR4) ligands created by modifying enzymes from lipid A synthesis pathways in Gram-negative bacteria. This study compares the ability of the biological and synthetic versions of these adjuvants to enhance the efficacy of recombinant HA (rHA) antigens in mouse influenza virus challenge . Mice immunized with rHA adjuvanted with BECCs stimulate the humoral and cell-mediated arms of the immune system without exhibiting cytotoxicity/pyrogenicity. A robust HA-specific immunoglobulin subtype, especially IgG2a, respon...
Abstract The influenza A virus polymerase, consisting of a heterotrimer of three viral proteins, carries out both transcription and replication of the viral RNA genome . These distinct activities are regulated by viral proteins that vary in abundance during infection, and by various co-opted host cell proteins, which serve as targets for the development of novel antiviral interventions . However, little is known about which host proteins direct transcription and which replication. In this report, we performed a differential interactome screen to identify host proteins co-opted as either transcription- or replication-specific factors. We found that distinct sets of host proteins interact with the influenza polymerase as it carries out the different activities. We functionally characterised HMGB2 and RUVBL2 as replication-specific cofactors and RPAP2 as a transcription-specific cofactor. Our data demonstrate that comparative proteomics can be used as a targeted approach to uncover virus-...
{Excerpt} Time Period: May 25, 2025 - May 31, 2025 - H5 Detection : 10 sites ( 2.5% ) - No Detection : 389 sites ( 97.5% ) - No samples in last week : 52 sites (...) Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/nwss/rv/wwd-h5.html ____
{Excerpt} The SARS-CoV-2 saltation variant BA.3.2 , harbouring over 50 mutations relative to its ancestral BA.3 lineage , has recently drawn global attention (figure A). Notably, BA.3.2 exhibits 44 mutations distinct from the currently dominant LP.8.1/LP.8.1.1 variant (appendix p 4), raising speculation about its potential to drive an outbreak similar to BA.2.86 /JN.1, particularly following its first detection outside South Africa in the Netherlands on April 2, 2025.1–5 A critical evaluation of its antigenic profile and infectivity is essential to establish its likelihood of prevailing. (...) Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00308-1/fulltext?rss=yes ____
Abstract Introduction Middle East respiratory syndrome (MERS) is a zoonotic viral respiratory disease caused by the Middle East respiratory syndrome coronavirus (MERS-CoV), associated with severe clinical outcomes and high mortality. Objectives Our study examined the kinetics of anti-MERS-CoV IgM and IgG antibodies during the acute and convalescent phases of infection, focusing on their correlations with clinical variables such as age and viral load. Methods Serum samples were collected from PCR-confirmed MERS-CoV patients (n = 23) during both phases and compared to healthy controls (n = 23) using validated ELISA-based assays. Results IgM levels peaked in the acute phase and declined significantly in the convalescent phase , while IgG levels were sustained and markedly higher during recovery . Correlation analyses revealed positive relationships between antibody levels and patient age (acute IgM: r = 0.56, p < 0.01; convalescent IgG: r = 0.59, p < 0.01) and viral loads (acute IgM...
Abstract The highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b has rapidly disseminated globally , with mammalian infections reported in multiple species. Recent evidence of mammal-to-mammal transmission has heightened concerns about the virus’s potential adaptation to mammals . The polymerase basic 2 (PB2) protein E627K mutation appears to be of key importance for mammalian adaptation. We isolated an HPAI H5N1 clade 2.3.4.4b virus from wild birds in Korea with 96% E and 4% K at amino acid position 627 of PB2 . To investigate the genomic characteristics of this clade regarding mammalian adaptation, we studied the replication and transmission of the H5N1 virus in mice. Two experiments with different challenge-to-contact ratios were conducted to assess transmission dynamics and mutation development . In experiment 1, a 4:1 challenge-to-contact ratio resulted in 100% transmission among direct-contact mice , with all mice succumbing to the infection. In experiment 2, a 1:...
Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...
Abstract Nationwide surveillance of avian influenza viruses (AIVs) in live poultry markets across China has occurred since 2014, providing a resource for AIV prevalence and genetic diversity studies . Here we report that 3,237 of 18,425 samples from poultry were AIV positive (17.57%) between 2019 and 2023, with H9N2 being the dominant subtype . We developed an automated phylogeny-based nomenclature system to classify genetic clades of the dominant H9N2 lineage, the BJ94 lineage. Using this model, we found that ten haemagglutinin (HA) sub-subclades cocirculated in poultry and showed antigenic variation. In addition, 99.46% and 96.17% of H9N2 AIVs in 2021–2023 possessed human-receptor binding-related HA-L226 and human MxA-resistance-related NP-N52 mutations , respectively. H9N2 strains with these two mutations preferred human-type receptors and increased replication in human cells in vitro, regardless of the presence of PB2-V/K/E627. Moreover, H9N2 AIVs containing HA-L226, PB2-V/K627 and...
Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...
Abstract Highly pathogenic avian influenza virus (HPAIV) of H5 and H7 subtypes has emerged as one of the most important zoonotic pathogens in the 21st century with significant economic consequences. The recent outbreak of H5N1 avian influenza (AI) in dairy cattle highlighted the importance of early detection in managing and mitigating HPAIV outbreaks. A successful high-speed diagnostic response requires rapid site and specimen access, minimal time for test protocols, and prompt communication of the diagnostic results to government officials. A new diagnostic paradigm that consists of miniaturized extractor and qPCR instruments (EZextractor and EZcycler MiniQ), designed for mobile, on-site testing has been compared with a platform of benchtop instruments (QIAGEN RNeasy and QuantStudio 5) for detecting inactivated H5 avian influenza virus (AIV) spiked in raw milk samples. Two sets of experiments were performed: 1) 15 raw milk samples, obtained from 15 different farms, diluted with phosph...
Abstract Background A surge of cases of Corynebacterium diphtheriae infection was observed in reception centers for migrants in Europe beginning in the summer of 2022. Most of the cases were cutaneous , although some respiratory cases as well as one death were reported. A pan-European consortium was created to assess the clinical, epidemiologic, and microbiologic features of this outbreak. Methods We assessed cases of toxigenic C. diphtheriae infection that were reported in 10 European countries from January through November 2022. Data regarding countries of origin and transit routes were obtained from interviews with the patients. Whole-genome sequencing and antimicrobial-susceptibility testing were performed on bacterial isolates that were obtained from the patients. The phylogenetic relationships of the isolates and their antimicrobial-resistance genes were evaluated. Results A total of 363 toxigenic C. diphtheriae isolates were identified among 362 patients during the study period....
Abstract The global spread of the A/goose/Guangdong/1/96-lineage H5N1 highly pathogenic avian influenza (HPAI) viruses is accompanied by an expanded host range and the establishment of sustained viral transmission among dairy cattle . To evaluate if the evolving H5N1 viruses have changed tissue tropism over time, we compared the binding patterns of recombinant hemagglutinin (HA) proteins derived from clade 1 (A/Vietnam/1203/04, H5VN) and circulating clade 2.3.4.4b viruses detected from a wild bird (A/Eurasian Teal/Hong Kong/AFCD-HKU-23-14009-01020/2023, H5HK) and dairy cattle (A/bovine/Ohio/B24OSU-439/2024, H5OH). The HA protein of A(H1N1)pdm09 virus was included for comparison. Using bio-layer interferometry, H1 protein preferentially bound to the 2,6-linked sialoside 6'SLNLN while H5 proteins preferentially bound to the 2,3-linked sialoside 3'SLN. H5OH showed higher binding affinity to 3'SLN than H5HK and H5VN. The attachment pattern of H1 and H5 proteins to the respirato...
ABSTRACT Severe coronavirus disease 2019 (COVID-19) patients who require hospitalization are at high risk of invasive pulmonary mucormycosis . Amphotericin B (AmB), which is the first-line therapy for invasive pulmonary mucormycosis, has been shown to promote or inhibit replication of a spectrum of viruses. In this study, we first predicted that AmB and nystatin had strong interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins using in silico screening, indicative of drugs with potential therapeutic activity against this virus. Subsequently, we investigated the impact of AmB, nystatin, natamycin, fluconazole, and caspofungin on SARS-CoV-2 infection and replication in vitro. Results showed that AmB and nystatin actually increased SARS-CoV-2 replication in Vero E6, Calu-3, and Huh7 cells . At optimal concentrations, AmB and nystatin increase SARS-CoV-2 replication by up to 100- and 10-fold in Vero E6 and Calu-3 cells, respectively. The other antifungals t...
ABSTRACT H1 and H3 influenza A viruses (IAVs) circulating in European pigs are markedly distinct from those circulating in other global swine populations . These viruses exhibit significant genetic diversity , further expanded by periodic interspecies transmission of IAVs from humans into pigs , followed by sustained circulation. Several zoonotic IAV infections in humans in Europe have been associated with the 1C lineage of H1 IAVs . Given the predominance of H1 detections in pigs and their zoonotic potential, we quantified antigenic evolution of H1 viruses in European pigs using ferret and pig models and assessed diversity relative to swine IAV vaccine strains. Ferret and swine antisera comparisons revealed no significant differences in antibody responses . Viruses of the 1A.3.3.2 clade exhibited reduced cross-reactivity to human seasonal vaccine strains from 2009. Viruses of the 1B.1.2.2 clade showed no cross-reactivity to the 1978 human seasonal influenza viruses nor to candidate va...