Background/Objectives: Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Nirsevimab has demonstrated to be a promising tool for preventing severe RSV disease. Although clinical trials have demonstrated the efficacy of Nirsevimab in preventing severe RSV disease, evidence regarding its performance in real-world clinical settings is still limited due to its recent introduction. This study aims to fill this knowledge gap by evaluating the impact of Nirsevimab in a cohort of infants and determining its effectiveness in reducing the burden of RSV disease. Methods: A retrospective study of RSV hospitalizations was conducted in children under six months of age, between 1 October and 31 March, across four seasons: pre-COVID (2018–2019), COVID (2019–2020), post-COVID pre-Nirsevimab (2022–2023), and Nirsevimab season (2023–2024). Results: Nirsevimab demonstrated significant efficacy in reducing RSV-related hospitalizations in infants under six months of age. During the 2023/2024 season, following the introduction of Nirsevimab, there was a substantial reduction in RSV-related lower respiratory tract infection (LRTI) hospitalizations. Among infants under 3 months of age, hospitalizations decreased by 79.3% (IRR: 0.21, 95% CI: 0.12–0.34). In infants aged 3 to 6 months, there was a 66.9% reduction (IRR: 0.33, 95% CI: 0.15–0.64). Additionally, Nirsevimab decreased the severity of RSV cases with LRTI who required the support of equipment for sanitary use, further reducing overall healthcare burden. Conclusions: These results underscore Nirsevimab’s vital role in preventing severe RSV infections and hospitalizations, especially among the most vulnerable infants, positioning it as a critical advancement in pediatric respiratory care.

Background Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children aged ≤ 5 years and adults aged ≥ 60 years worldwide. Despite this, RSV-specific therapeutic options are limited. Rilematovir is an investigational, orally administered inhibitor of RSV fusion protein-mediated viral entry. Objective To establish the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir (low or high dose) in children aged ≥ 28 days and ≤ 3 years with RSV disease. Methods CROCuS was a multicenter, international, double-blind, placebo-controlled, randomized, adaptive phase II study, wherein children aged ≥ 28 days and ≤ 3 years with confirmed RSV infection who were either hospitalized (Cohort 1) or treated as outpatients (Cohort 2) were randomized (1:1:1) to receive rilematovir (low or high dose) or placebo. Study treatment was administered daily as an oral suspension from days 1 to 7, with dosing based on weight and age groups. The primary objective was to establish antiviral activity of rilematovir by evaluating the area under the plasma concentration–time curve of RSV viral load in nasal secretions from baseline through day 5. Severity and duration of RSV signs and symptoms and the safety and tolerability of rilematovir were also assessed through day 28 (± 3). Results In total, 246 patients were randomized, treated, and included in the safety analysis population (Cohort 1: 147; Cohort 2: 99). Of these, 231 were included in the intent-to-treat-infected analysis population (Cohort 1: 138; Cohort 2: 93). In both cohorts, demographics were generally similar across treatment groups. In both cohorts combined, the difference (95% confidence interval) in the mean area under the plasma concentration–time curve of RSV RNA viral load through day 5 was - 1.25 (- 2.672, 0.164) and - 1.23 (- 2.679, 0.227) log₁₀ copies∙days/mL for the rilematovir low-dose group and the rilematovir high-dose group, respectively, when compared with placebo. The estimated Kaplan–Meier median (95% confidence interval) time to resolution of key RSV symptoms in the rilematovir low-dose, rilematovir high-dose, and placebo groups of Cohort 1 was 6.01 (4.24, 7.25), 5.82 (4.03, 8.18), and 7.05 (5.34, 8.97) days, respectively; in Cohort 2, estimates were 6.45 (4.81, 9.70), 6.26 (5.41, 7.84), and 5.85 (3.90, 8.27) days, respectively. A similar incidence of adverse events was reported in patients treated with rilematovir and placebo in Cohort 1 (rilematovir: 61.9%; placebo: 58.0%) and Cohort 2 (rilematovir: 50.8%; placebo: 47.1%), with most reported as grade 1 or 2 and none leading to study discontinuation. The study was terminated prematurely, as the sponsor made a non-safety-related strategic decision to discontinue rilematovir development prior to full recruitment of Cohort 2. Conclusions Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need. Clinical Trial Registration EudraCT Number: 2016-003642-93; ClinicalTrials.gov Identifier: NCT03656510. First posted date: 4 September, 2018.

Background/Objectives: Respiratory illnesses frequently lead to hospitalization in adults aged 60 and older, especially due to respiratory viral infectious (RVI). This study investigates hospitalization patterns and characteristics of RVI at HM Hospitals from October 2023 to March 2024; Methods: We retrospectively explored hospitalizations of patients aged 60 years and older with RVIs, gathering data on demographics, clinical profiles, comorbidities, and treatments. Outcomes included hospitalization, ICU admissions, and mortality, and independent factors associated with outcomes were identified using a multi-state model; Results: From October 2023 to March 2024, from a total of 3258 hospitalizations, 1933 (59.3%) were identified as positive for RVIs. Overall, SARS-CoV-2 was the most prevalent (52.6%), followed by influenza (32.7%), and RSV (11.8%). Most RVI involved single infections (88.2%). Hospitalization rates increased with age for SARS-CoV-2 (333.4 [95% CI: 295.0–375.2] to 651.6 [95% CI: 532.1–788.4]), influenza (169.8 [95% CI: 142.6–200.7] to 518.6 [95% CI: 412.1–643.1]), and RSV (69.2 [95% CI: 52.2–90.0] to 246.0 [95% CI: 173.8–337.5]), with SARS-CoV-2 showing the highest rate, followed by influenza and RSV. In the multi-state model, RSV infection significantly increased ICU admission risk (HR: 2.1, 95%, p = 0.037). Age on admission (HR: 1.1, 95%, p < 0.001) and Charlson score (HR: 1.4, 95%, p = 0.001) were associated with transitioning from admission to death. ICU to death risks included age at admission (HR: 1.7, 95%, p < 0.001); Conclusions: RVI in adults 60 years and older are associated with high hospitalization and mortality rates, primarily driven by influenza and SARS-CoV-2, followed by RSV. Age and comorbidities significantly impact disease severity, emphasizing the need for targeted prevention and management strategies for RSV in this vulnerable population.

Background/Objectives: Respiratory syncytial virus (RSV) represents a significant cause of acute respiratory infections (ARIs) in adults aged 60 years and older, often leading to severe clinical outcomes and high healthcare costs. This study aimed to evaluate the clinical and economic burden of RSV compared to other ARIs, focusing on specific age groups, comorbidities, and demographic factors. Methods: A retrospective observational study was conducted using the electronic medical records of adults aged ≥60 years hospitalized for ARIs, including RSV, in Spain. Direct costs related to hospitalizations, intensive care unit (ICU) admissions, and treatments were analyzed. The study also assessed demographic, clinical, and comorbidity-related factors influencing the economic burden. Results: RSV infections resulted in significantly higher direct costs compared to other ARIs, particularly in patients aged 70–80 years. Comorbidities such as asthma and smoking history were associated with increased costs in RSV cases. Although ICU costs were comparable between groups, hospitalizations for RSV required longer stays and more intensive treatments, amplifying the overall economic burden. Differences in costs by age and sex highlighted the need for tailored clinical management strategies. Conclusions: RSV poses a substantial economic and clinical burden on adults aged 60 years and older, particularly in those with comorbidities. Preventive measures, such as vaccination, could reduce healthcare costs and improve outcomes in this vulnerable population. These findings support the inclusion of RSV vaccines in immunization programs, especially in aging populations like Spain, to alleviate healthcare pressures during peak respiratory disease seasons.

(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate.

In this phase III, open label, single arm, multicenter clinical study, we report safety, tolerability and immunogenicity of PHH-1V as a booster dose in subjects primary vaccinated against COVID-19 with the BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S vaccines, with or without previous COVID-19 infection. A total of 2661 subjects were included in this study and vaccinated with the PHH-1V vaccine. Most treatment-emergent adverse events (TEAE) were solicited local and systemic reactions with grade 1 (58.70%) or grade 2 (27.58%) intensity, being the most frequently reported injection site pain (82.83%), fatigue (31.72%) and headache (31.23%). Additionally, immunogenicity was assessed at Baseline and Days 14, 91, 182 and 365 in a subset of 235 subjects primary vaccinated. On Day 14, geometric mean triter (GMT) in neutralizing antibody against SARS-CoV-2 Wuhan and Beta, Delta and Omicron BA.1 variants increased in all primary vaccination with a geometric mean fold raise (GMFR) of 6.90 (95% CI 4.96-9.58), 12.27 (95% CI 8.52-17.67), 7.24 (95% CI 5.06-10.37) and 17.51 (95% CI 12.28-24.97), respectively. Despite GMT decay after day 14, it remains in all cases significatively higher from baseline up to 1 year after PHH-1V booster administration and GMFR against Beta and Omicron BA.1 variants over 3 at 1 year after booster compared to baseline. PHH-1V booster vaccination elicited also a significant RBD/Spike-specific IFN-γ ⁺ T-cell responses on Day 14. Overall, PHH-1V vaccine was immunogenic and well-tolerated regardless of the previous primary vaccination scheme received with no reported cases of severe COVID-19 infection throughout the entire study.