Daily Respiratory Research Analysis

UNLABELLED: The epithelial cilia are the first line of defense against respiratory pathogens. For the first time, we found that Kallikrein-related peptidase 13 (KLK13), a serine protease expressed in airway ciliated epithelial cells with cell type specificity, was secreted into nasal mucus. KLK13 efficiently cleaved the spike of SARS-CoV-2, resulting in the inhibition of SARS-CoV-2 cell entry and spike protein-mediated cell-cell fusion. Recombinant KLK13 protease efficiently cleaved the spike protein as well as virus particles IMPORTANCE: Epithelial cilia directly come into contact with inhaled pathogens. The nasal mucus functions as a formidable barrier against penetration of viral particles. KLK13 is secreted into nasal mucus and efficiently cleaves the spike proteins across different coronavirus species. KLK13-mediated cleavage of spike inhibits SARS-CoV-2 entry and syncytium formation. Intranasally delivered KLK13 also restricts SARS-CoV-2 infection

IMPORTANCE: Long COVID is characterized by persistent symptoms after SARS-CoV-2 infection, with inflammation playing a key role in pathogenesis. Colchicine, an established anti-inflammatory agent, may reduce these symptoms by targeting inflammatory pathways. OBJECTIVE: To evaluate the superiority of colchicine over placebo in improving functional outcome at 52 weeks from baseline. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, 1:1 randomized clinical trial recruited participants with confirmed SARS-CoV-2 infection and persistent symptoms from 8 hospitals in 6 states in India between January 2022 and July 2023. Individuals were eligible if they had functional limitation (Post-COVID-19 Functional Status scale grade 2 or more) and/or elevated inflammatory markers (high-sensitivity C-reactive protein >0.20 mg/dL and/or neutrophil to lymphocyte ratio >5). Outcomes were assessed at 12, 26, and 52 weeks after randomization. Data were analyzed from January to February 2025. INTERVENTIONS: Participants were randomly assigned to receive colchicine, 0.5 mg, once or twice daily, based on body weight, or placebo for 26 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in distance walked during a 6-minute walk test from baseline to 52 weeks. Secondary outcomes included changes in inflammatory markers and patient-reported outcome measures, such as quality of life, anxiety, depression, fatigue, dyspnea, measured using validated instruments. RESULTS: Of 346 participants included in the modified intention-to-treat analysis, 209 (60.4%) were female, 137 (39.6%) were male, and the mean (SD) age was 46 (12) years. At 52 weeks, there was no difference in mean (SD) change in 6-minute walk test distance between the colchicine and placebo groups (colchicine, 35.5 [19.76] m; placebo, 29.96 [19.83] m; mean difference, 5.59 m; 95% CI, -9.00 to 20.18; P = .45). Similar null findings were seen across all predefined outcomes, except for a small, nonclinically relevant difference in the mean (SD) ratio of forced expiratory volume in 1 second to forced vital capacity (colchicine, -0.02 [0.03]; placebo, -0.06 [0.03]; mean difference, 0.04; 95% CI, 0.02 to 0.07; P = .001). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among adults with long COVID, colchicine did not improve functional capacity, respiratory function, or inflammatory markers. These findings underscore the need to explore alternative therapeutic approaches for long COVID. TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI/2021/11/038234.

OBJECTIVES: Older adults are vulnerable to infection and are difficult to diagnose. This study assessed the performance of MeMed BV (MMBV), a host-protein test for differentiating bacterial from viral infection, in adults ≥65 years. METHODS: Post hoc pooled and meta-analysis of adults with suspected acute infections enrolled in 3 prospective studies. MMBV results were interpreted as bacterial/viral/equivocal per manufacturer's instructions. Reference standard infection etiology was adjudicated by experienced physicians who were blinded to MMBV. Diagnostic accuracy for bacterial infection was calculated for MMBV results (area under the receiver operating characteristic curve [AUC], bin analysis) and for unequivocal MMBV results (sensitivity/specificity). MMBV's potential impact on antibiotic use was estimated by comparing MMBV-guided decisions to actual practice. RESULTS: A total of 754 younger (18-64 years) and 248 older (≥65 years) adults were included. Among older adults, the median age was 75.0 years (IQR, 69.0, 82.0), 53.2% were male, 68.1% were hospitalized, and 79.0% had ≥3 comorbidities. Respiratory tract infections were common (76.2%), and 85.1% were prescribed antibiotics. A total of 111 patients were assigned a bacterial reference standard infection etiology, 77 a viral etiology, and 60 an indeterminate etiology. In pooled analysis, MMBV attained comparable AUC in older (0.95; 95% CI, 0.92-0.98) vs younger adults (0.95; 0.93-0.97). Focusing on older adults, 96.2% (90.3-98.8) sensitivity and 85.7% (74.8-92.5) specificity with 10.6% equivocal results were observed. MMBV could reduce potentially unwarranted antibiotic prescriptions 2.5-fold (from 62.3% to 24.7%; CONCLUSIONS: MMBV demonstrated high diagnostic accuracy in older adults, supporting its potential to optimize antibiotic use in this population. Further studies are needed to evaluate real-world utility.