Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia(SCAP).We prospectively enrolled consecutive SCAP patients admitted to ICU.Bronchoscopy was performed at bedside within 48 h of ICU admission,and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid.The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy.Sixty-seven patients were included.Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota(R2=0.033;P=0.018),followed by acute kidney injury(AKI;R2=0.032;P=0.011)and plasma MIP-1βlevel(R2=0.027;P=0.044).Random forest identified that the families Prevotellaceae,Moraxellaceae,and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results.Multivariable Cox regression showed that the increase inα-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements.The positive bacteria lab test results,AKI,and plasma MIP-1βlevel were associated with patients’lung microbiota composition on ICU admission.The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.

Clinical Efficacy of Inhaled Nitric Oxide in Preventing the Progression of Moderate to Severe COVID-19 and Its Correlation to Viral Clearance:Results of a Pilot Study

Hypoxic patients with coronavirus disease 2019(COVID-19)are at high risk of adverse outcomes.Inhaled nitric oxide(iNO)has shown anti-viral and immunomodulatory effects in vitro.However,in vivo evidence of efficacy in hypoxic COVID-19 is sparse.This open label feasibility study was conducted at a single referral center in South India and evaluated the effectiveness of repurposed iNO in improving clinical outcomes in COVID-19 and its correlation with viral clearance.We recruited hypoxemic COVID-19 patients and allocated them into treatment(iNO)and control groups(1:1).Viral clearance on day 5 favored the treatment group(100%vs 72%,P<0.01).The speed of viral clearance as adjudged by normalized longitudinal cycle threshold(Ct)values was positively impacted in the treatment group.The proportion of patients who attained clinical improvement,defined as a≥2-point change on the World Health Organization ordinal scale,was higher in the iNO cohort(n=11,79%)as compared to the control group(n=4,36%)(odds ratio 6.42,95%confidence interval 1.09–37.73,P=0.032).The proportion of patients progressing to mechanical ventilation in the control group(4/11)was significantly higher than in the treatment group(0/14).The all-cause 28-day mortality was significantly different among the study arms,with 36%(4/11)of the patients dying in the control group while none died in the treatment group.The numbers needed to treat to prevent an additional poor outcome of death was estimated to be 2.8.Our study demonstrates the putative role of repurposed iNO in hypoxemic COVID-19 patients and calls for extended validation.