Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

Relationship Between Endogenous Hydrogen Sulfide and Pulmonary Vascular Indexes on High-Resolution Computed Tomography in Patients with Chronic Obstructive Pulmonary Disease.

Objective: To explore the relationship between endogenous hydrogen sulfide (H2S) and high-resolution computed tomography (HRCT) indexes in pulmonary vascular remodeling. Methods: A total of 94 stable chronic obstructive pulmonary disease (COPD) patients were recruited for the study．Plasma H2S levels were measured using fluorescence probe. Fluorescence quantitative polymerase chain reaction was used to measure H2S synthase cystathionine-γ-lyase (CSE) mRNA and cystathionine-ß-synthesis enzyme (CBS) mRNA. The main pulmonary artery diameter (mPAD), axial diagonal mPAD, coronal mPAD, sagittal mPAD, right pulmonary artery diameter (RPAD), left pulmonary artery diameter (LPAD), and ascending aortic diameter (AAD) and the percentage of total cross-sectional area of vessels less than 5 mm2 of total lung area (%CSA <5) on HRCT were measured. Pulmonary arterial systolic pressure (PASP) of echocardiography, blood gas analysis, and routine blood tests were performed. Correlation analysis and multivariate linear regression were performed using SPSS 22.0. Results: H2S was negatively correlated with mPAD, axial diagonal mPAD, and sagittal mPAD (r = -0.25~-0.32) and positively correlated with PaO2 (r = 0.35). Relative expression of CSE mRNA was positively correlated with PASP, coronal mPAD, sagittal mPAD, white blood cell count (WBC), and neutrophil count (N) (r = 0.30~0.44). The relative expression of CBS mRNA was positively correlated with PASP, WBC, and N (r = 0.34~0.41). In separate models predicting pulmonary vascular indexes, a 1µmol/L increase in H2S predicted lower pulmonary artery diameter (for axial diagonal mPAD, 0.76mm lower; for mPAD/AAD, 0.68mm lower). All P values were less than 0.05. Conclusion: Endogenous H2S may be involved in pulmonary vascular remodeling, providing a new method for the diagnosis and treatment of COPD. The generation of H2S may be inhibited by hypoxia, inflammation, etc.

Impact of obstructive sleep apnea on pulmonary hypertension in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) syndrome are highly prevalent respiratory conditions. Their coexistence is referred to as the overlap syndrome. They are both related to pulmonary hypertension (PH) development. This study investigated the effects of OSA on PH in patients with COPD and the associated factors. METHODS: Consecutive patients with stable COPD were recruited for an observational cross-sectional study from September 2016 to May 2018 at Peking University Third Hospital. In total, 106 patients with COPD were enrolled and performed home portable monitoring and echocardiography. OSA was defined by an apnea hypopnea index (AHI) ≥10 events/h. Based on OSA absence or presence, patients were divided into the COPD with OSA and COPD without OSA groups. Factors affecting pulmonary artery pressure (PAP) and PH were identified using univariate analysis and logistic regression models. RESULTS: In the 106 patients with COPD, the mean age was 69.52 years, 91.5% were men, and the mean forced expiratory volume in 1 s (FEV1) percentage of predicted was 56.15%. Fifty-six (52.8%) patients with COPD were diagnosed with OSA, and 24 (22.6%) patients with COPD were diagnosed as PH. Compared with COPD without OSA group, the median PAP in COPD with severe OSA group increased by 5 mmHg (36.00 [26.00-50.00] mmHg vs. 31.00 [24.00-34.00] mmHg, P = 0.036). COPD with percent of night-time spent with oxygen saturation below 90% (T90) > 10% group had higher PAP than COPD with T90 ≤ 1% group (36.00 [29.00-50.00)] mmHg vs. 29.00 [25.50-34.00] mmHg, F = 7.889, P = 0.007). Univariate analysis revealed age, FEV1% predicted, T90, and Charlson index had statistically significant effects on PH. Multiple regression analysis showed a significant and independent effect of both FEV1% predicted (odds ratio [OR] = 3.46; 95% confidence interval [CI]: 1.15-10.46; P = 0.028) and AHI (OR = 3.20; 95% CI: 1.09-19.35; P = 0.034) on PH. CONCLUSIONS: Patients with COPD with OSA are more susceptible to PH, which is associated with declining lung function and increased severity of OSA. Thus, nocturnal hypoxemia and OSA in elderly patients with COPD should be identified and treated.

Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with Non-alcoholic Fatty Liver Disease and Chronic Hepatitis B.

Chronic liver disease is associated with lipid metabolic disruption. We carried out a study to determine serum lipidomic features of patients with non-alcoholic fatty liver disease (NAFLD) and active chronic hepatitis B (CHB) and explored the biomarkers for non-alcoholic steatohepatitis (NASH). Serum lipidomic profiles of healthy controls (n = 23) and of biopsy-proven NAFLD (n = 42), CHB with NAFLD (n = 22) and without NAFLD (n = 17) were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. There were distinct serum lipidome between groups of NAFLD and CHB without NAFLD. Most of the neutral lipids and ceramide were elevated in the NAFLD group but were decreased in the CHB without NAFLD group. Plasmalogens were decreased in both groups. Triacylglycerols (TAGs) with lower carbon numbers and double bonds were increased in subjects with NASH. Serum monounsaturated TAG was a significant predictor of NASH (OR = 3.215; 95%CI 1.663-6.331) and positively correlated with histological activity (r = 0.501; P < 0.001). It showed good predictability for NASH in the NAFLD group [area under the receiver operating characteristic curves (AUROC) = 0.831] and was validated in the CHB group (AUROC = 0.833); this characteristic was superior to that of cytokeratin-18 and alanine transaminase. The increase in monounsaturated TAG might be a specific marker for NASH in both NAFLD and CHB patients.

Association between non-invasively diagnosed hepatic steatosis and chronic kidney disease in Chinese adults on their health check-up.

OBJECTIVE: To explore the association between chronic kidney disease (CKD), graded by the estimated glomerular filtration rate (eGFR), and non-alcoholic fatty liver disease (NAFLD) using controlled attenuation parameter (CAP) and fatty liver index (FLI) values in Chinese adults undergoing routine health examinations. METHODS: A total of 731 adult participants without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included. Their eGFR, CAP, FLI and abdominal ultrasonography results were assessed. RESULTS: The prevalence of ultrasound-diagnosed NAFLD and CKD (eGFR <60 mL/min per 1.73 m2 ) was 36.1% and 6.6%, respectively. CKD was more common in NAFLD patients than in those without (10.6% vs 4.3%, P < 0.001). The CAP and FLI values were significantly higher in the NAFLD group than in those without, but the change in the eGFR was negligible between the two groups. eGFR was negatively correlated with CAP (r = -0.189, P = 0.003) and FLI values (r = -0.130, P = 0.045). Moreover, eGFR was significantly lower in participants with CAP >292 dBm or FLI ≥60 than in those with CAP <238 dBm or FLI <30, respectively (both P < 0.05). The CAP value (odds ratio [OR] 1.099, 95% confidence interval [CI] 1.091-1.108, P = 0.021) was an independent risk factor for CKD. CONCLUSIONS: A diagnosis of hepatic steatosis is related to an increased risk of CKD among non-alcoholic and non-diabetic Chinese adults regardless of whether the diagnosis was acquired via ultrasound, CAP or FLI. Increased hepatic lipid content may contribute to CKD development.

Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B.

AIM: To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD). METHODS: A cohort of Han patients with biopsy-proven CHB, with or without NAFLD (CHB group, n = 51; CHB + NAFLD group, n = 57), and normal controls (normal group, n = 47) were recruited from Northern (Tianjin), Central (Shanghai), and Southern (Zhangzhou) China. Their PNPLA3 polymorphisms were genotyped by gene sequencing. The association between PNPLA3 polymorphisms and susceptibility to NAFLD, and clinical characteristics of NAFLD were evaluated on the basis of physical indices, liver function tests, glycolipid metabolism, and histopathologic scoring. The association of PNPLA3 polymorphisms and hepatitis B virus (HBV) load was determined by the serum level of HBV DNA. RESULTS: After adjusting for age, sex, and body mass index, we found that four linked single nucleotide polymorphisms (SNPs) of PNPLA3, including the rs738409 G allele (CHB + NAFLD group vs CHB group: odds ratio [OR] = 2.77, 95% confidence interval [CI]: 1.18-6.54; P = 0.02), rs3747206 T allele (CHB + NAFLD group vs CHB group: OR = 2.77, 95%CI: 1.18-6.54; P = 0.02), rs4823173 A allele (CHB + NAFLD group vs CHB group: OR = 2.73, 95%CI: 1.16-6.44; P = 0.02), and rs2072906 G allele (CHB + NAFLD group vs CHB group: OR = 3.05, 95%CI: 1.28-7.26; P = 0.01), conferred high risk to NAFLD in CHB patients. In patients with both CHB and NAFLD, these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis (NASH) (NAFLD activity score ≥ 3; P = 0.01-0.03) and liver fibrosis (> 1 Metavir grading; P = 0.01-0.04). As compared to those with C/C and C/G at rs738409, C/C and C/T at rs3747206, G/G and G/A at rs4823173, and A/A and A/G at rs2072906, patients in the CHB + NAFLD group with G/G at rs738409, T/T at rs3747206, A/A at rs4823173, and G/G at rs2072906 showed significantly lower serum levels of HBV DNA (P < 0.01-0.05). CONCLUSION: Four linked SNPs of PNPLA3 (rs738409, rs3747206, rs4823173, and rs2072906) are correlated with susceptibility to NAFLD, NASH, liver fibrosis, and HBV dynamics in CHB patients.