This study evaluated the effectiveness of Moderna's updated mRNA-1273 vaccine targeting the KP.2 variant, compared to people who did not receive any 2024-2025 COVID-19 vaccine, in preventing COVID-19-associated hospitalizations and medically-attended COVID-19 among adults aged≥18years in the United States during the 2024-2025 season. Data were extracted from linked administrative healthcare claims and electronic health records (EHR) for vaccinations from 23 August 2024 through 23 April 2025 and followed through 30 April 2025. We conducted a retrospective matched cohort study with propensity score weighting to adjust for differences between groups to assess vaccine effectiveness (VE) against COVID-19 outcomes. VE was calculated as 1 minus the hazard ratio (HR) from Cox proportional hazards models. Overall, 596,248 mRNA-1273 KP.2 vaccine recipients were matched 1:1 to unexposed adults. The mean (standard deviation) age was 63 (17) years, with more than half of the population being 65years or older. Approximately 70% of individuals had an underlying medical condition making them high-risk for severe outcomes for COVID-19. VE was 52.8% [95% confidence interval (CI) 34.8%, 65.8%] against COVID-19-related hospitalization and 39.4% (35.0%, 43.5%) against medically-attended COVID-19 over a median follow-up of 55 (interquartile range 32-77) days in an interim analysis. The VE was sustained throughout the entire study period and shown to be 45.2% (37.7%, 51.8%) against COVID-19-related hospitalizations and 33.1% (30.6-35.4%) against medically-attended COVID-19 over a median follow-up of 127 (interquartile range 84-173) days. The mRNA-1273 KP.2 vaccine demonstrated significant incremental effectiveness in preventing hospitalization with COVID-19 and medically-attended COVID-19 in adults during the 2024-2025 season to date. The VE was sustained with longer median follow up time. These findings support ongoing vaccination efforts to mitigate the public health impact of COVID-19.

Haemophilus influenzae is a human-specific Gram-negative bacterium responsible for respiratory tract infection, sepsis, and meningitis. The study aimed to investigate the epidemiology, serotypedistribution, and mechanisms of beta-lactam resistance among invasive H.influenzae strains isolated in Poland from 2018 to 2023. Invasive H.influenzae isolates were received from patients with positive culture results from blood, cerebrospinal fluid (CSF), and pleural fluid. Sample data were obtained from the Polish laboratory surveillance system. For all isolates screening test for beta-lactam resistance was performed and the minimum inhibitory concentrations (MICs) of clinically relevant antibiotics were determined using antibiotic gradient strips. For isolates with inhibition zone P1U < 12mm (n = 133), whole genome sequencing (WGS) analysis was performed. Most strains of H.influenzae were isolated from blood (90.7%). Non-typeable Hinf (NTHi) strains were responsible for most invasive disease in all age groups and accounted for 85.7% (342/399) of all cases. Capsulated isolates constituted 14.3%; among them the most common serotype was typef (Hif; 64.9%), followed by serotypes: e (Hie; 19.3%), b (Hib; 14.0%), and d (Hid; 1.8%). Of the 399 isolates collected between 2018 and 2023, 15.8% and 1.0% were resistant to ampicillin and cefotaxime, respectively. Resistance to meropenem and ciprofloxacin using the meningitis breakpoint was detected in 4.3% and 1.8% strains, respectively. All isolates showed susceptibility to chloramphenicol. Resistance to rifampicin characterized 3.8% of isolates tested. The Cefinase test revealed beta-lactamase production in 8.8% of isolates. In our study NTHi predominated among invasive cases across all age groups, especially among elderly patients, similarly to other countries. β-Lactam resistance among studies strains has remained stable over the years. Recently, however, resistance to third-generation cephalosporins has emerged. Continuous surveillance and a rational antibiotic policy are essential to address H.influenzae resistance.

The clinical presentation of critically ill patients with coronavirus disease 2019 (COVID-19) has evolved significantly with the emergence of the Omicron variant. Current intensive care unit (ICU) admissions involve patients with diverse comorbidities and immune statuses, highlighting the need to redefine homogeneous phenotypic subgroups within this population. This study aimed to characterize distinct clinical phenotypes among critically ill patients with COVID-19 and acute respiratory failure. This multicenter prospective substudy of the SEVARVIR cohort included adult patients from 39 French ICUs between December 2021 and October 2024 with acute respiratory failure and infected with the Omicron variant. Clustering analysis was conducted using Kohonen's self-organizing maps (SOMs) and validated with ClinTrajan, two unsupervised clustering methods, to identify homogeneous patient phenotypes. During the study period, 777 patients with Omicron infection were included, and 7 distinct clinical clusters were identified. Clusters 1 and 2 included patients with metabolic and cardiovascular comorbidities. Cluster 3 featured younger, mildly ill patients with isolated chronic respiratory failure, while cluster 4 comprised older male patients with isolated respiratory failure. Cluster 5 included patients with isolated hematologic malignancies, cluster 6 patients with multiorgan failure, and cluster 7 organ transplant recipients, with high severity scores and impaired renal function. ICU management varied substantially across clusters. Patients in clusters 5 and 7 had the highest requirements for organ support, with frequent use of invasive mechanical ventilation, vasopressors (cluster 6), and renal replacement therapy (cluster 7). Dexamethasone and tocilizumab were most commonly prescribed in cluster 4 (91.3% and 30.2%, respectively). Mortality at day 28 varied significantly across clusters, ranging from 13.1% in cluster 3 to 41.1% in cluster 6. This clustering analysis highlights, for the first time, the clinical heterogeneity of critically ill patients infected with Omicron, identifying seven distinct clusters with varying clinical presentations, management strategies and outcomes. These findings underscore the relevance of a phenotype-driven approach to support personalized treatment strategies and guide future clinical trials. Clinicaltrials.gov, NCT05162508. A Graphical Abstract is available for this article.

SARS-CoV-2, influenzaA and B, and respiratory syncytial virus (RSV) are the major seasonal viruses that can cause severe illness. Rapid and accurate diagnosis of these viruses may improve patient management and surveillance efforts. Here, we assessed the diagnostic performance of the STANDARD M10 Flu/RSV/SARS-CoV-2 Fast (M10Fast) real-time polymerase chain reaction assay for near-patient diagnosis of the four viruses. This retrospective validation study included 600 nasopharyngeal swab specimens previously tested using the standard-of-care laboratory-based Allplex Respiratory Panels1-4 and Allplex SARS-CoV-2/FluA/FluB/RSV reference assays. Of these samples, 300 were positive for SARS-CoV-2, influenzaA, influenzaB, or RSV, while the remaining 300 samples were negative for the four viruses. Positive and negative percent agreements between the M10Fast index and reference tests were the primary endpoints. Additionally, analytical sensitivity of the M10Fast in terms of 95% limit of detection was estimated via serial dilutions of a positive reference material. Of 600 samples processed in the M10Fast, 590 (98.3%) were fully concordant. Positive percent agreement coefficients were 98.7% for influenzaA and 100% for SARS-CoV-2, influenzaB, and RSV. Negative percent agreement was 99.2% for influenzaA, 99.4% for both SARS-CoV-2 and RSV, and 99.8% for influenzaB. Discordant results were characterized by low viral loads with cycle threshold values of 38 or greater. The rate of invalid M10Fast runs was low (1.2%). Limit of detection of the M10Fast varied from 189copies/mL for RSV to 541copies/mL for the N gene of SARS-CoV-2. The M10Fast, developed for near-patient settings, reliably detects SARS-CoV-2, FluA, FluB, and RSV in 36min and its performance is comparable to standard laboratory-based assays.

Infections caused by metallo-β-lactamase-producing Enterobacterales offer limited therapeutic options. Aztreonam-avibactam (ATM-AVI) provides a promising alternative, but its approved intermittent regimen is complex and can lead to substantial drug waste. We describe a case of mastoiditis with a retrotympanic abscess due to OXA-48- and NDM-1-producing Klebsiella pneumoniae, managed with continuous infusion (CI) of ATM-AVI after a full-vial loading dose, supported by therapeutic drug monitoring (TDM) and whole-genome sequencing (EPISEQ CS V2.0, bioMérieux). A 35-year-old man previously treated abroad for meningitis and brain abscesses presented with residual deep-seated infection caused by OXA-48- and NDM-1-producing K.pneumoniae. After initial treatment with ceftazidime-avibactam plus aztreonam, therapy was switched to ATM-AVI using a full-vial loading dose followed by CI. TDM demonstrated sustained plasma levels of both drugs, and the patient improved without adverse events. CI of ATM-AVI following a high loading dose was feasible, safe, and allowed optimized pharmacokinetic/pharmacodynamic (PK/PD) exposure while preventing drug wastage. Larger studies are warranted to determine the clinical utility of CI ATM-AVI across different MIC ranges.

Pertussis or whooping cough, caused by the bacteria Bordetella pertussis, is ahighly contagious respiratory disease. Over the past century, whole-cell pertussis (wP) and acellular pertussis (aP) vaccines were developed andwidely adopted, leading to a substantial reduction in the number of pertussis cases. Currently, various strategies are employed to protect different segments of the population, including primary immunization, toddler and school-age boosters, adult boosters, and vaccination in pregnancy (ViP). Nonetheless, pertussis remains a global health challenge with periodic outbreaks occurring every 2-5years. The non-pharmacological measures implemented during the COVID-19 pandemic resulted in a drastic reduction in the circulation of B. pertussis. However, post-pandemic, there has been a resurgence in pertussis cases. This review aims to explore the post-pandemic global pertussis outbreaks and identify underlying trends to gain insights into the potential contributing factors. As of June 2025, pertussis outbreaks with diverse epidemiological patterns have been reported in at least 42 countries, including 30 aP and 12 wP vaccine-using countries. Some common observations among these countries include low infant immunization rates and an absence of vaccination programs for specific populations such as school-aged children, adults, and pregnant individuals. Additionally, in countries with extensive immunization schedules and high vaccination uptake, outbreaks have occurred in regions with low vaccination coverage rates (VCRs). Multiple interrelated factors may have contributed to the post-pandemic pertussis outbreaks, such as the cyclic epidemiology of pertussis, low VCR, waning vaccine-derived immunity, low uptake of boosters, and lack of lifelong protection through regular boosters. To effectively mitigate the incidence of pertussis outbreaks, it is crucial to administer regular booster vaccinations throughout an individual's lifetime, with particular emphasis on at-risk populations and pregnant individuals.A Graphical Abstract is available for this article.

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with acute-on-chronic liver failure (ACLF). Cytokines play essential roles in the pathogenesis of IPA and have been identified as promising diagnostic biomarkers. This study aimed to conduct a comprehensive proof-of-concept evaluation of the diagnostic potential of cytokines for IPA in patients with ACLF. In this single-center prospective study, patients with HBV-ACLF were categorized into IPA (with diagnostic criteria of probable IPA, n = 16), bacterial pneumonia (BP, n = 32), and non-infection (n = 32) groups. Groups were matched for age, gender, and liver decompensation severity. Plasma cytokines, interleukin (IL)-33, IL-17A, IL-23, IL-31, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, interferon-γ, tumor necrosis factor alpha, and soluble IL-2 receptor, were quantified. Diagnostic accuracy was assessed via ROC analysis. IL-33 levels were markedly elevated in IPA vs. BP (163.07 [108.30-211.22] vs. 12.82 [4.24-50.55]pg/mL; P < 0.001) and non-infection groups (163.07 [108.30-211.22] vs. 4.24 [4.24-52.51]pg/mL; P < 0.001). ROC analysis identified IL-33 as a strong diagnostic marker for IPA (AUC =0.871; sensitivity 93.80%, specificity 84.40%; P < 0.001) with optimal cutoff at 66.97pg/mL. Furthermore, IL-33 levels were significantly elevated during IPA development compared to both the incubation phase (154.86 vs. 8.29pg/mL, P = 0.005) and the recovery phase (154.86 vs. 28.01pg/mL, P = 0.038). Plasma IL-33 demonstrates high accuracy in diagnosing IPA and differentiating it from bacterial infections in patients with HBV-ACLF, offering a minimally invasive diagnostic tool. Graphical abstract available for this article.

Antibiotic discovery and antibiotic prescribing represent two domains that both stand to benefit from artificial intelligence (AI)-driven progress in the near future. In this article, we discuss these parallel advances and the potential future synergy between AI-enabled antibiotic discovery and AI-assisted antibiotic prescribing. Although multiple challenges remain before these two domains meaningfully converge, their integration could amplify the strengths of each: discovery pipelines generating broader, more diverse classes of antibacterial agents, and prescribing tools capable of matching these agents to individual patients with unprecedented precision. Such a scenario could transform antibiotic therapy by enabling AI-supported, patient-specific treatment decisions while reinforcing the principles of precision medicine and antimicrobial stewardship.

Long COVID-related fatigue affects a large number of people across the world, with increasing numbers of people experiencing long-term disability as a consequence. We tested the feasibility of a self-help version of a manual osteopathic approach initially developed for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to treat people with long COVID-related fatigue. Our feasibility study assessed recruitment into a 1:1 randomized controlled trial (RCT) to receive (i) self-help intervention (self-massage, mobility, flexibility, and breathing exercises, and alternating cold and warm packs to the top of the spine) or (ii) wait-list control group. Follow-up was assessed by online surveys at 3 and 6months (indicating retention). Verbal feedback was obtained from participants. Of the 138 eligible survey participants, 126 (90.6%) agreed to participate in two RCTs, achieving the required sample size of 100. Follow-up rates of 79.3% and 59.4% were achieved at 3 and 6months, respectively. Improvements in Chalder Fatigue Questionnaire (CFQ) scores were observed in both groups between 0 and 3months (- 4.6 and - 2.9, respectively), to a greater degree in the intervention group (p = 0.01). Feedback showed a cohort keen to engage with the intervention, although some found the intervention onerous at times. We have reported the results of a feasibility study examining a potentially beneficial intervention for people with long COVID. There were indications of benefit in a patient group with often intractable symptoms. Based on this feasibility study, we believe that the low-cost self-help intervention in isolation could help support fatigue reduction in some people. This has implications for the treatment of both long COVID and ME/CFS. International Standard Randomized Controlled Trial Number (ISRCTN): 99840264.

There is a gap in the understanding of the burden of respiratory syncytial virus (RSV) among adults in low, lower-middle, and upper-middle income countries, particularly with regard to up-to-date epidemiological data. Meta-analyses were conducted to determine pooled estimates of RSV prevalence among high-risk 18-59-year-old adults and ≥ 50-year-old adults with or without risk factors or comorbidities, who present with respiratory illnesses in low, lower-middle, and upper-middle income countries. Using studies identified from a previously described systematic literature review, a random-effects model was used to determine pooled prevalence for each study population. Subgroup analyses and meta-regression were conducted using the moderator variables deemed most relevant a priori and a mixed-effects approach. Pooled RSV prevalence estimates were 5.1% (95% confidence interval [CI] 3.9-6.6%) and 3.9% (95% CI 3.3-4.7%) across 33 studies in 18-59-year-old high-risk adults with respiratory illnesses and 66 studies in ≥ 50-year-old adults with respiratory illnesses, respectively. Subgroup analyses for 18-59-year-old high-risk adults found geography, study setting, and respiratory illness to collectively explain ~ 54% of the variation in RSV prevalence estimates. The diagnostic method for RSV was found to explain ~ 8% of the variation in RSV prevalence estimates in ≥ 50-year-old adults; no other factors explored via subgroup analyses for ≥ 50-year-old adults had a notable effect on variation. For both populations, a substantial level of residual heterogeneity was observed using Higgin's I2 when studies were split for subgroup analyses. Overall, there is a considerable disease burden associated with RSV among 18-59-year-old high-risk and ≥ 50-year-old adults with respiratory illnesses in low, lower-middle, and upper-middle income countries, highlighting the need for improved prevention programs for RSV in these populations.