Background: Patients with COVID-19 may experience hypoxemic Acute Respiratory Failure (hARF) requiring O2-therapy by High-Flow Nasal Cannula (HFNO). Although Prone Positioning (PP) may improve oxygenation in COVID-19 non-intubated patients, the results on its clinical efficacy are controversial. The present study aims to prospectively investigate whether PP may reduce the need for endotracheal intubation (ETI) in patients with COVID-19 receiving HFNO. Methods: All consecutive unselected adult patients with bilateral lung opacities on chest X-ray receiving HFNO after admission to a SARS-CoV-2 Respiratory Intermediate Care Unit (RICU) were considered eligible. Patients who successfully passed an initial PP trial (success group) underwent PP for periods ≥ 2 h twice a day, while receiving HFNO. The study’s primary endpoint was the intubation rate during the stay in the RICU. Results: Ninety-three patients were included in the study. PP was feasible and safe in 50 (54%) patients. Sixteen (17.2%) patients received ETI and 27 (29%) escalated respiratory support, resulting in a mortality rate of 9/93 (9.7%). The length of hospital stay was 18 (6–75) days. In 41/50 (80%) of subjects who passed the trial and underwent PP, its use was associated with clinical benefit and survival without escalation of therapy. Conclusions: PP is feasible and safe in over 50% of COVID-19 patients receiving HFNO for hARF. Randomized trials are required to confirm that PP has the potential to reduce intubation rate.

IntroductionAir pollution is a risk factor for respiratory infections and asthma exacerbations. We previously reported impaired Type-I and Type-III interferons (IFN-β/λ) from airway epithelial cells of preschool children with asthma and/or atopy. In this study we analyzed the association between rhinovirus-induced IFN-β/λ epithelial expression and acute exposure to the principal outdoor air pollutants in the same cohort.MethodsWe studied 34 children (17asthmatics/17non-asthmatics) undergoing fiberoptic bronchoscopy for clinical indications. Bronchial epithelial cells were harvested by brushing, cultured and experimentally infected with Rhinovirus Type 16 (RV16). RV16-induced IFN-β and λ expression was measured by quantitative real time PCR, as was RV16vRNA. The association between IFNs and the mean exposure to PM10, SO2 and NO2 in the day preceding bronchoscopy was evaluated using a Generalized Linear Model (GLM) with Gamma distribution.ResultsAcute exposure to PM10 and NO2 was negatively associated to RV16-induced IFNβ mRNA. For each increase of 1ug/m3 of NO2 we found a significative decrease of 2.3x103 IFN-β mRNA copies and for each increase of 1ug/m3 of PM10 a significative decrease of 1x103 IFN-β mRNA copies. No significant associations were detected between IFN-λ mRNA and NO2 nor PM10. Increasing levels of NO2 (but not PM10) were found to be associated to increased RV16 replication.ConclusionsShort-term exposure to high levels of NO2 and PM10 is associated to a reduced IFN-β expression by the airway epithelium, which may lead to increased viral replication. These findings suggest a potential mechanism underlying the link between air pollution, viral infections and asthma exacerbations.

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SARS-CoV-2 may lead to a large spectrum of respiratory manifestations, including pulmonary sequelae. We conducted a single-center longitudinal study of survivors from severe COVID-19 cases who underwent a chest CT during hospitalization (CTH). Three months after being discharged, these patients were evaluated by a clinical examination, pulmonary function tests and a chest-CT scan (CTFU). Sixty-two patients were enrolled. At follow-up, 27% complained of exertional dyspnoea and 12% of cough. Dyspnoeic patients had a lower forced expiratory flow (FEF)25–75 (p = 0.015), while a CT scan (p = 0.016 showed that patients with cough had a higher extent of bronchiectasis. Lung volumes and diffusion of carbon monoxide (DLCO) at follow-up were lower in patients who had been invasively ventilated, which correlated inversely with the length of hospitalization and ground-glass extension at CTH. At follow-up, 14.5% of patients had a complete radiological resolution, while 85.5% presented persistence of ground-glass opacities, and 46.7% showed fibrotic-like alterations. Residual ground-glass at CTFU was related to the length of hospitalization (r = 0.48; p = 0.0002) and to the need for mechanical ventilation or high flow oxygen (p = 0.01) during the acute phase. In conclusion, although patients at three months from discharge showed functional impairment and radiological abnormalities, which correlated with a prolonged hospital stay and need for mechanical ventilation, the persistence of respiratory symptoms was related not to parenchymal but rather to airway sequelae.