SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies.

Background: Haemophilus influenzae (Hi) and Haemophilus parainfluenzae (Hpi) are common nasopharyngeal flora, yet both are potential lower airway pathogens, especially if mucociliary clearance is abnormal, such as in people with primary ciliary dyskinesia (pwPCD). Methods: Retrospective data analysis of medical records, between 2013 and 2023, collecting demographic, clinical and microbiological data to assess prevalence and clinical impact. Results: Throughout the observation period, the number of pwPCD attending the clinic increased from 19 to 49; median [interquartile range (IQR)] patient age was 10 years (5–15), and 28 (57%) were males. A total of 403 sputum cultures were tested, with a median (IQR) of 33 (11–52) per year and 7 (4–14) per patient. Hi prevalence increased from 0% to 35% (P = 0.01), and from 5% to 53% for Hpi (P < 0.01). Of all clinic patients, 27 (55%) ever had Hi and 36 (73%) ever had Hpi positive cultures. Co-infection occurred in 24 (49%) patients, while 11 patients (22.4%) never had either Hi or Hpi isolated. Median (IQR) age at first isolation was 9 years (4.5–16) for Hi, and 8 years (4–16) for Hpi, P = not significant. Both sexes were equally infected. Chronic infection occurred in 33% of pwPCD with Hi, and 34% for Hpi. Median forced expiratory volume in 1 second, percent predicted (FEV1%pred) was unaffected by infection with Hi or Hpi alone but decreased postcoinfection by a median (IQR) of −4% (−7 to −2), measured from 1 year before until 1 year after coinfection (P = 0.02). Conclusions: Hi and Hpi prevalence increased in our PCD cohort over time. One-third of patients were chronically infected, yet had an insignificant influence on lung function.

E-cigarette use, or vaping, is increasing in prevalence, especially among adolescents. There is a paucity of information on the impact of e-cigarette aerosols on lung health, particularly to the airway protective components. In this study, disruptions to airway protective functions in response to increasing repetitive exposure to nicotine-free e-cigarette aerosols were examined. The recovery capability of the airway defence was also investigated. Cultured primary nasal airway cells from five healthy individuals were exposed to repetitive exposures to e-cigarette aerosols. Cilia function was analysed via high-speed video microscopy, while epithelial barrier integrity was assessed through trans-epithelial electrical resistance measurements and immunofluorescence. Cytokine secretion was assessed using multiplex screening. Significant impairment in cilia function and epithelial barrier integrity was observed after 24 or more vaping exposures. Cilia beating frequency declined by 18.6% (6.78 ± 0.23 Hz) after 24 sessions and by 53.0% (3.91 ± 0.27 Hz) after 60 sessions (p < 0.01). Trans-epithelial electrical resistance values dropped by 45.6% (315.37 ± 13.38 Ωcm²) after 24 sessions and by 77.4% (131.29 ± 6.84 Ωcm²) after 60 sessions (p < 0.01). Nicotine-free aerosols disrupted Occludin-1 and ZO-1 expression but not E-cadherin. Cytokine analysis showed increased secretion of IL-1ra, IL-6, FGF-basic, IFN-γ, and VEGF following 36 vaping sessions. Recovery experiments indicated cilia function normalised within 48 h, while epithelial barrier required up to 72 h. Repetitive vaping progressively impairs airway protective functions in vitro. While cilia function and epithelial integrity recover in the short term, the delay may increase susceptibility to infections.