Daily Respiratory Research Analysis

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are closely related pathogens responsible for a significant burden of acute respiratory infections. Interactions between RSV and hMPV have been hypothesized, but the mechanisms of interaction are largely unknown. Here, we use a mathematical model to quantify the likelihood of interactions from population-level surveillance data and investigate whether interactions could lead to increases in hMPV burden under RSV medical interventions, including active and passive immunization. In Scotland, Korea, and three regions of Canada, annual hMPV outbreaks lag RSV outbreaks by up to 18 weeks; two Canadian regions show patterns consistent with out-of-phase biennial outbreaks. Using a two-pathogen transmission model, we show that a negative effect of RSV infection on hMPV transmissibility can explain these dynamics. We use post-pandemic RSV-hMPV rebound dynamics as an out of sample test for our model, and the model with interactions better predicts this period than a model where the pathogens are assumed to be independent. Finally, our model suggests that hMPV peak timing and magnitude may change under RSV interventions. Our analysis provides a foundation for detecting possible RSV-hMPV interactions at the population level, although such a model oversimplifies important complexities about interaction mechanisms.

BACKGROUND: Our study addresses the pressing need for safe and effective treatments for pneumonia in young children caused by respiratory syncytial virus (RSV) and bacterial co-infections. This issue is particularly urgent given the absence of targeted RSV therapies and the growing threat of antibiotic resistance associated with managing bacterial co-infections. METHODS: We conducted a double-blind, randomized clinical trial (ClinicalTrials.gov: NCT05929599) at Vietnam National Children's Hospital to evaluate nasal-spraying Bacillus spore probiotics (LiveSpo Navax containing B. subtilis ANA4 and B. clausii ANA39 at ≥1 billion CFU/mL) in children aged 1-24 months with pneumonia due to RSV and bacterial co-infection. Participants were randomly assigned in a 1:1 ratio to receive standard care plus either LiveSpo Navax or physiological saline solution, using a simple sealed-number draw at enrollment. Primary outcomes were the median duration required to resolve common pneumonia symptoms, duration of oxygen therapy, and total treatment days. RESULTS: A total of 120 children are enrolled (60 per group). In the final analysis, 50 participants in the Control group and 51 in the Navax group are included. The trial is completed with no serious adverse events or treatment-related side effects in either group. Navax treatment shortens the duration of eight symptoms associated with RSV pneumonia by one day, oxygen therapy by two days, and overall treatment by one day. CONCLUSIONS: The nasal-spraying Bacillus spore approach presents a safe, effective, and fast treatment for young children with pneumonia due to RSV and bacterial co-infections, making it especially a promising strategy for resource-limited settings. Pneumonia is a common lung infection caused by both respiratory syncytial virus (RSV) and harmful bacteria. While antibiotics are generally effective in treating the infection, their overuse has contributed to growing antibiotic resistance. In this study, we show that LiveSpo Navax-a probiotic spray containing billions of Bacillus spores (beneficial bacteria that can survive tough conditions)-is safe and helpful for children with pneumonia. Spraying LiveSpo Navax directly into the noses of children helped reduce their symptoms, RSV and bacterial infections, as well as the need for antibiotics. This affordable, simple, and fast treatment offers a promising way to support recovery from pneumonia, especially in areas with limited access to healthcare.

BACKGROUND: Pneumocystis jirovecii pneumonia (PjP) is a rising cause of acute respiratory failure in immunocompromised patients, often requiring Intensive Care Unit (ICU) admission. However, optimal ventilatory strategies remain unclear. METHODS: For the present study, we conducted an ancillary analysis of the PRONOCYSTIS study, a large multicenter cohort of PjP patients. Patients admitted to the ICUs were compared according to initial respiratory management (High-Flow Nasal Cannula (HFNC), standard Oxygen (SO) or Non-Invasive Ventilation (NIV). A propensity score adjustment [inverse probability of treatment weighting (IPTW) analysis] was implemented to account for potential confounders. The primary outcome was intubation rate. Univariable and multivariable Cox regressions were also used to assess variables associated with survival. RESULTS: Over the study period, 248 patients with PjP were included in the present analysis. Of those, 70 were treated by HFNC while 118 and 60 received SO and NIV, respectively. HFNC patients had a decreased intubation rate (28.6% versus 45.0% in NIV and 55.4% in SO patients; p = 0.003). When assessing the impact of respiratory management on intubation by IPTW, HFNC remained an independent protective factor (weighted Hazard Ratio (HR) 0.41 (95% CI 0.24-0.69); p < 0.001). While, NIV was not associated with intubation (HR 0.62 (95% CI 0.37-1.02); p = 0.056). Through adjusted survival analysis, long-term corticosteroids treatment (aHR 4.03 (95% CI 2.01-8.08); p < 0.001), Solid tumor (aHR 3.37 (95% CI 1.45-7.86); p = 0.005) and the Sequential Organ Failure Assessment score (aHR 1.24 (95% CI 1.15-1.35); p < 0.001) were found to be independent predictor for death. Initial respiratory support was not associated with survival either in the Cox multivariable analysis or in the IPTW analysis. CONCLUSION: Through this multicenter observational study of severe PjP patients, although oxygenation strategy was not associated with D90 survival, HFNC support appeared to be associated with a lower intubation rate. Further prospective studies are warranted to refine respiratory management in critically ill PjP patients.