SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes.

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.

Respiratory syncytial virus prophylaxis in infants with congenital airway anomalies compared to standard indications and complex medical disorders.

An observational study was conducted of children < 2 years who received ≥ 1 dose of palivizumab in 32 Canadian institutions from 2005 to 2017. We compared respiratory illness (RIH) and respiratory syncytial virus-related hospitalization (RSVH) hazards in children with a congenital airway anomaly (CAA) versus those prophylaxed for standard indications (SI) and serious medical disorders (SMD). Data were assembled on neonatal course, demographics, palivizumab utilization and adherence, and respiratory illness events, and analyzed using ANOVA, chi-square tests and Cox proportional hazards. Twenty-five thousand three children (1219 CAA, 3538 SMD, and 20,246 SI) were enrolled. Palivizumab adherence was 74.8% overall and similar across groups. For 2054 respiratory-related events, 1724 children were hospitalized. RIH rates were 13.6% (CAA), 9.6% (SMD), and 6.0% (SI). RSVH rates were 2.4% (CAA), 1.6% (SMD), and 1.5% (SI). After adjustment for demographic and neonatal differences, children with a CAA had a significantly increased RIH and RSVH hazard relative to SI (RIH, HR = 1.6, 95% CI 1.2-2.2, p = 0.002; RSVH, HR = 2.1, 95% CI 1.0-4.4, p = 0.037) but similar to SMD (RIH, HR = 1.3, 95% CI 0.9-1.9, p = 0.190; RSVH, HR = 1.7, 95% CI 0.7-4.1, p = 0.277).Conclusion: Children with a CAA experience higher RIH risk. RSVH hazard was similar between CAA and SMD but higher for CAA compared to SI, implying that this population requires surveillance for RSV prophylaxis. What is Known: • Children with congenital airway anomalies (CAA) are at risk for respiratory tract illness and respiratory syncytial virus-related hospitalization (RSVH) with accompanying morbidity and mortality • RSV prophylaxis may be useful in children with a CAA, but is not routinely recommended What is New: • Children with a CAA had a 1.6-2.3 fold greater risk of respiratory-related hospitalization and RSVH compared to those prophylaxed for standard, approved indications and serious medical disorders. • RSVH risk in children aged < 2 years with either upper or lower airway anomalies is similar. Children with a CAA require careful surveillance during the RSV season and prophylaxis may be appropriate.