Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening cardiovascular disorder characterized by complex multisystem disturbances. Although alterations in the gut microbiota have been reported in IPAH, how the gut virome interacts with bacterial communities and host metabolism remains unclear. We enrolled 28 patients with IPAH and 30 age-matched healthy controls (HCs). Fecal viromes and bacteriomes were profiled by metagenomic sequencing, and serum metabolomic data were integrated to construct virus–bacterium–metabolite interaction networks. Random forest models were used to evaluate the diagnostic potential of virome features. IPAH patients exhibited markedly reduced gut virome diversity (Shannon, Simpson, and Pielou indices, p < 0.05) and distinct community structures from HCs (p < 0.01). A total of 499 differential viral operational taxonomic units (vOTUs) were identified, accompanied by extensive reorganization of interaction networks. At the phylum level, Hofneiviricota was enriched and Phixviricota depleted, both correlating with clinical indicators. Virus–bacterium associations were markedly increased in IPAH (44,894 vs. 17,920, r > 0.5). Notably, vOTU2967, vOTU1924, and vOTU4522 were elevated and inversely related to Bacteroides, whose depletion was associated with increased lactic acid levels. Mediation analysis confirmed significant indirect virus–bacterium–metabolite effects (p < 0.05). Random forest models based on vOTUs or viral families effectively distinguished IPAH patients from controls, highlighting the exploratory potential of gut virome features for mechanistic insights. IPAH is characterized by reduced virome diversity, altered viral taxa, and reorganized virus–bacterium–metabolite networks. These findings suggest that gut viruses may influence disease progression by modulating bacterial metabolism, providing a potential avenue for biomarker discovery and therapeutic intervention.

OBJECTIVES:To compare the function of positive end-expiratory pressure (PEEP) titration guided by transpulmonary pressure (Ptp) with traditional lung-protective ventilation to optimize pulmonary arterial compliance (Cpa) in acute respiratory distress syndrome (ARDS) patients. DESIGN:A single center, randomized controlled pilot pathophysiological study. SETTING:A respiratory ICU in China. PATIENTS/SUBJECTS:Adult patients diagnosed with ARDS who had received invasive mechanical ventilation for less than 72 hours. INTERVENTIONS:Patients were randomized to the Ptp group or empirical low tidal volume lung-protective group. MEASUREMENTS AND MAIN RESULTS:The primary endpoint was the difference in the Cpa dynamic changes between the two groups during the first 72 hours of intervention following enrollment. A total of 40 patients were included in the study, with 20 patients in the Ptp group and 20 patients in the control group. The Cpa in the Ptp group was 3.98 ± 0.46 mL/mm Hg at randomization, which was not significantly different from that in the control group (3.89 ± 0.40 mL/mm Hg). The Cpa in the Ptp group was significantly higher than that in the control group (p = 0.039) during the 72 hours of dynamic monitoring performed after enrollment. However, Cpa did not change significantly over time, and there was no significant difference in the trend between the two groups. There was a significant difference in the dynamic change of the right ventricular ejection fraction and oxygen delivery index between the two groups within 72 hours after randomization (p < 0.05). The change in the right ventricular end-diastolic transverse diameter/left ventricular end-diastolic transverse diameter ratio and in the tricuspid annular plane systolic excursion was significantly different between the two groups (p < 0.05). CONCLUSIONS:Ptp-guided PEEP titration was superior to traditional lung-protective ventilation in maintaining a higher Cpa and preserving right ventricular function in patients with moderate-to-severe ARDS caused by pneumonia.

Pneumocystis is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised hosts, with increasing incidence in HIV-negative individuals. Although the gut mycobiota has emerged as a critical regulator of distal immunity, its role in HIV-negative Pneumocystis pneumonia (PCP) remains entirely unexplored. We established a murine model of Pneumocystis murina infection and performed full-length internal transcribed spacer (ITS) sequencing to characterize longitudinal changes in gut fungal communities over five weeks. Untargeted metabolomics was conducted on plasma samples to identify systemic metabolic alterations. To investigate causality, gut fungal communities were depleted using fluconazole, and fecal microbiota transplantation (FMT) was performed in germ-free mice to assess the functional role of gut fungi in modulating pulmonary immune responses. While α diversity of the gut mycobiota remained unchanged, β diversity analysis revealed significant structural alterations beginning week 3 (w3) post-infection, coinciding with peak pulmonary fungal burden. Linear discriminant analysis effect size identified Purpureocillium lilacinum and Talaromyces verruculosus as enriched opportunistic taxa. Untargeted metabolomics demonstrated marked metabolic reprogramming at w3, with significant perturbations in glycine, serine, and threonine metabolism, as well as the tricarboxylic acid cycle. Fluconazole-mediated depletion of gut fungi significantly increased pulmonary Pneumocystis burden and exacerbated lung inflammation, accompanied by reduced pulmonary Th1 cell responses. Critically, FMT from fluconazole-treated donors into germ-free mice recapitulated the exacerbated phenotype, confirming that gut fungal dysbiosis is sufficient to impair Th1-mediated antifungal immunity and worsen disease severity. This study establishes, for the first time, that gut fungal dysbiosis actively contributes to the pathogenesis of HIV-negative PCP via the gut-lung axis. Our findings reveal that commensal gut fungi support pulmonary Th1 immune responses essential for controlling PCP, and their disruption exacerbates disease. These results provide new insights into the gut mycobiota as a potential therapeutic target in PCP and caution against indiscriminate antifungal use in susceptible populations.

Background The use of extracorporeal membrane oxygenation (ECMO) has expanded significantly, especially during the COVID-19 pandemic, but membrane lung (ML) function at high altitudes remains unexplored. This study aimed to determine whether ML oxygen delivery (V’O2ML) capacity during ECMO is lower in high-altitude Xining than at low-altitude Beijing in China. Methods In this prospective observational study, patients who received ECMO were categorized into the Xining or Beijing group based on treatment center. Patients were monitored for ML gas transfer on the third day of ECMO, and clinical outcomes were compared between the two groups. Results Sixty patients were enrolled, 30 in each group. V'O2ML was significantly lower in the Xining group than in the Beijing group (171 [130-203] ml/min vs. 210 [178-255] ml/min, p = 0.002). Mortality at 60 days showed no significant difference, but ML failure was higher in the Xining group (26.7% vs 6.7%, p = 0.038). V'O2ML was positively correlated with post-ML arterial partial pressure of oxygen (PaO2), hemoglobin, and fibrinogen and negatively correlated with D-dimer (all p < 0.001). Older age (OR, 1.075; 95% CI, 1.020-1.132, p = 0.007) and lower V’O2ML capacity (OR, 0.984; 95% CI, 0.974-0.995, p = 0.005) were independent risk factors for 60-day mortality. The optimal V'O2ML cutoff for survival was ≥205ml/min, with higher V'O2ML associated with better outcomes (p < 0.001). Conclusions High altitude is associated with lower V’O2ML capacity during ECMO, although it does not appear to increase short-term mortality. V'O2ML is an essential prognostic factor, and further research with larger cohorts and dynamic monitoring of V'O2ML across different altitudes is recommended. Trial Registration ClinicalTrials.Gov: NCT06152744. Registered 22 November 2023

Background Long COVID (coronavirus disease) poses a substantial challenge to individual and global public health. In the context of China's Omicron wave, key aspects such as its long-impact on non-hospitalized adults, the role of reinfection and other pathogenic infections during recovery require updated evidence. Therefore, the aim of this study is to delineate factors associated with long COVID and create a robust predictive model for primary-care to identify individuals at high risk of long COVID, utilizing data collected during the Omicron wave. Methods This study employed an online survey to assess SARS-CoV-2 infection status and track long COVID symptoms 9 to 15 months post-initial infection in 2099 participants. Associated factors of long COVID were identified through univariable and multivariable logistic regression analyses.The long COVID risk prediction model was visualized using a nomogram, and its performance was evaluated using the area under the curve (AUC) and a calibration curve. Results An analysis of 1,408 valid responses revealed that 35.9% of participants reported persistent long COVID symptoms 9 to 15 months after their initial SARS-CoV-2 infection. During the rehabilitation period, SARS-CoV-2 re-infection and other respiratory infections were reported in 32.4% and 34.3% of cases, respectively. The most prevalent long COVID symptoms were as follows: fatigue (16.2%), cough (9.0%), decreased activity tolerance (7.3%), shortness of breath (6.0%), expectoration (5.8%), and forgetfulness (5.7%). Multivariable analysis identified the factors independently associated with long COVID: female gender, absence of comorbidities, frequency of SARS-CoV-2 infections, history of other respiratory infections, and the presence of seven acute symptoms. Using logistic regression analysis, we developed a nomogram for long COVID prediction, which achieved an AUC of 0.731. Additional subgroup analysis revealed that participants with either SARS-CoV-2 reinfection or other pathogenic respiratory infections were more likely to report both a higher number of long COVID symptoms and increased symptom severity. Conclusions In summary, to mitigate the risk of long COVID, it is critical to prevent SARS-CoV-2 reinfection and other respiratory infections during the post-infection period. We developed a user-friendly nomogram model with satisfactory predictive performance to evaluate the risk of long COVID among COVID-19 patients.

Background The coronavirus disease 2019 (COVID-19) pandemic increased the demand for reliable tests to predict disease severity and mortality. Methods In training cohort, we obtained traditional clinical data and plasma proteomics performed using the Olink proteomics platform from 52 fatal COVID-19 cases (COVID-19-F), 50 severe COVID-19 cases (COVID-19-S), 55 moderate/mild COVID-19 cases (COVID-19-M), and 54 healthy controls. Receiver operating characteristic (ROC) curves and logistic regression were applied to judge the accuracy of biomarkers to predict in-hospital mortality and build combined panel. An independent external cohort was used for validation. Results In total, 19 clinical parameters and 92 proteins were assessed. Traditional clinical indices did not show adequate predictive value of short-term mortality in severe COVID-19. In proteomics analysis, 75 proteins were differentially expressed among the four groups. Pathway analysis revealed an imbalance of inflammatory responses and excessive immunity in COVID-19-F. Subsequently, a novel plasma biomarker panel (including interleukin 8 and osteoprotegerin) was developed, with AUC values of 0.791 and 0.781 when comparing COVID-19-F to COVID-19-M or COVID-19-S, respectively. The predictive power of the panel was verified in an external cohort. Conclusions Our standardized assays yielded a prediction panel of mortality during hospitalization in patients with COVID-19.

BACKGROUND:Tuberculosis (TB) is one of the deadliest infectious diseases worldwide, causing millions of new cases and deaths annually. Rapid and accurate TB diagnostics are essential for TB control, yet current methods do not fully meet global needs. Peripheral blood neutrophils play a critical role in TB infection and represent a promising source of diagnostic markers. METHODS:We conducted a cross-sectional proteomic analysis to characterise neutrophil protein profiles in individuals with active TB (ATB), latent TB infection (LTBI), and healthy controls (HC). Stringent criteria were applied to identify differentially expressed proteins (DEPs) among these groups. Transcriptomic data were integrated to perform pathway enrichment analysis of DEPs. Three DEPs (B2M, TXN, and PRDX5) were further validated as candidate diagnostic biomarkers for Mycobacterium tuberculosis (MTB) infection using automated western blotting in a cohort of 319 individuals, including 71 ATB, 142 LTBI, and 106 HC. FINDINGS:Hundreds of DEPs were identified across the three groups. Integrated transcriptomic analysis revealed significant enrichment of DEPs in the NOD-like receptor signalling pathway. Receiver operating characteristic analysis of the three-protein combination (B2M, TXN, and PRDX5) yielded an area under the curve of 0.9847, with a sensitivity of 95.11% and a specificity of 96.23% for detecting MTB infection. INTERPRETATION:This study presents a comprehensive proteomic profile of neutrophils under different MTB infection states, and this three-protein combination may assist in the diagnosis of MTB infection. FUNDING:This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-037) and the National Science and Technology Major Project of China (20212017ZX10201301-002-003).

Nirmatrelvir-ritonavir (NMV-r) has been widely used to treat coronavirus disease 2019 (COVID-19) for a standard period of 5-days. However, there are increasing reports of patients with persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity after the standard 5-day course of NMV-r treatment. Moreover, the clinical characteristics of these patients and the efficacy of extending NMV-r treatment duration are not fully understood. We conducted a prospective study involving hospitalized patients with COVID-19. In total, 310 patients were included: 133 with SARS-CoV-2 RNA positivity after completion of the standard course of NMV-r (positive group) and 177 without SARS-CoV-2 positivity (negative group). A subset of patients (n = 37) in the positive group extended the treatment with NMV-r. Patients in the positive group had higher severity scores, neutrophil counts, lactate dehydrogenase levels, and viral loads at admission. Following the standard 5-day NMV-r course, the positive group showed a significantly increased risk of composite disease progression outcomes (hazard ratio [HR] 3.35, 95% confidence interval [CI]: 2.07-5.44; p < 0.0001). This group also demonstrated higher risks of 28-day all-cause mortality, initiation of invasive mechanical ventilation, intensive care unit (ICU) admission and prolonged hospitalization. However, no significant differences in clinical outcomes were observed between the standard and the extended treatment groups in the unadjusted analysis. After adjustment for baseline characteristics, the extended treatment group demonstrated significantly better outcomes compared with the standard treatment group. Specifically, the extended treatment group had lower rates of composite disease progression (HR: 0.39, 95% CI: 0.20-0.79; p = 0.009), invasive mechanical ventilation (HR: 0.24, 95% CI: 0.08-0.73; p = 0.01), and ICU admission (HR: 0.15, 95% CI: 0.02-0.94; p = 0.04), along with a shorter length of hospital stay (HR: -13.54, 95% CI: -26.01 to -1.07; p = 0.033). SARS-CoV-2 positivity after NMV-r treatment is common and associated with worse clinical outcomes. Extending NMV-r therapy may reduce disease progression risk; this finding requires confirmation in future studies.

BACKGROUND:Approximately 10-30% of individuals continue to experience symptoms classified as post-acute sequelae of coronavirus disease 2019 (COVID-19 (PASC)). PASC is a multisystem condition primarily characterized by respiratory symptoms, such as reduced diffusing capacity for carbon monoxide (DLco). Although many studies have investigated the pathogenesis of acute COVID-19, the long-term molecular changes in COVID-19 convalescents with PASC remain poorly understood. METHODS:We prospectively recruited 70 individuals who had been diagnosed with COVID-19 from 7 January 2020 to 29 May 2020 (i.e., COVID-19 convalescents); we performed follow-up visits at 6 months, 1 year, 2 years, and 3 years after hospital discharge. Thirty-five healthy controls (CONs), recruited from a physical examination center before the COVID-19 pandemic, served as a comparison group. We explored the proteomic and metabolomic profiles of 174 plasma samples from the 70 COVID-19 convalescents and 35 CONs. RESULTS:We performed a comprehensive molecular analysis of COVID-19 convalescents to investigate host changes up to 3 years after hospital discharge. Our multi-omics analysis revealed activation of cytoskeletal organization and glycolysis/gluconeogenesis, as well as suppression of gas transport and adaptive immune responses, in COVID-19 convalescents. Additionally, metabolites involved in glutathione metabolism; alanine, aspartate, and glutamate metabolism; and ascorbate and aldarate metabolism were significantly upregulated in COVID-19 convalescents. Pulmonary and molecular abnormalities persisted for 3 years in COVID-19 convalescents; impaired diffusing capacity for carbon monoxide (DLco) was the most prominent feature. We used this multi-omics profile to develop a model involving one protein (heterogeneous nuclear ribonucleoprotein K (HNRNPK)) and two metabolites (arachidonoyl-EA and 1-O-(2r-hydroxy-pentadecyl)-sn-glycerol)) for identification of COVID-19 convalescents with abnormal DLco. CONCLUSIONS:These data provide insights concerning molecular sequelae among COVID-19 convalescents up to 3 years after hospital discharge, clarify mechanisms driving respiratory sequelae, and support the development of a novel model to predict reduced DLco. This longitudinal multi-omics analysis may illuminate the trajectory of altered lung function in COVID-19 convalescents.

BACKGROUND:Severe pneumonia has a poor prognosis and high mortality. Current severity scores such as Acute Physiology and Chronic Health Evaluation (APACHE-II) and Sequential Organ Failure Assessment (SOFA), have limited ability to help clinicians in classification and management decisions. The goal of this study was to analyse the clinical characteristics of severe pneumonia and develop a machine learning-based mortality-prediction model for patients with severe pneumonia. METHODS:Consecutive patients with severe pneumonia between 2013 and 2022 admitted to Beijing Chaoyang Hospital affiliated with Capital Medical University were included. In-hospital all-cause mortality was the outcome of this study. We performed a retrospective analysis of the cohort, stratifying patients into survival and non-survival groups, using mainstream machine learning algorithms (light gradient boosting machine, support vector classifier and random forest). We aimed to construct a mortality-prediction model for patients with severe pneumonia based on their accessible clinical and laboratory data. The discriminative ability was evaluated using the area under the receiver operating characteristic curve (AUC). The calibration curve was used to assess the fit goodness of the model, and decision curve analysis was performed to quantify clinical utility. By means of logistic regression, independent risk factors for death in severe pneumonia were figured out to provide an important basis for clinical decision-making. RESULTS:A total of 875 patients were included in the development and validation cohorts, with the in-hospital mortality rate of 14.6%. The AUC of the model in the internal validation set was 0.8779 (95% CI, 0.738 to 0.974), showing a competitive discrimination ability that outperformed those of traditional clinical scoring systems, that is, APACHE-II, SOFA, CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥65 years), Pneumonia Severity Index. The calibration curve showed that the in-hospital mortality in severe pneumonia predicted by the model fit reasonably with the actual hospital mortality. In addition, the decision curve showed that the net clinical benefit was positive in both training and validation sets of hospitalised patients with severe pneumonia. Based on ensemble machine learning algorithms and logistic regression technique, the level of ferritin, lactic acid, blood urea nitrogen, creatine kinase, eosinophil and the requirement of vasopressors were identified as top independent predictors of in-hospital mortality with severe pneumonia. CONCLUSION:A robust clinical model for predicting the risk of in-hospital mortality after severe pneumonia was successfully developed using machine learning techniques. The performance of this model demonstrates the effectiveness of these techniques in creating accurate predictive models, and the use of this model has the potential to greatly assist patients and clinical doctors in making well-informed decisions regarding patient care.

Background: Adjuvant corticosteroids are effective in patients with human immunodeficiency virus (HIV)-associated Pneumocystis jirovecii pneumonia (PCP) patients, but the effectiveness of adjuvant corticosteroids in non-HIV PCP remained controversial. This study aimed to evaluate the effectiveness of standard-dose compared with low-dose steroids in non-HIV PCP patients with acute respiratory distress syndrome (ARDS). Methods: This retrospective observational study included non-HIV PCP patients with ARDS admitted to the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital from 2015 to 2022. Demographics, clinical characteristics, and outcomes were compared between patients receiving standard-dose and those receiving low-dose steroids. Survival times were assessed using Kaplan-Meier curves and compared with the Log rank test. Cox proportional hazards regression analysis was conducted to identify independent risk factors for 28-day and 60-day mortality. Results: A total of 105 non-HIV PCP with ARDS were included, with 48 patients in the standard-dose steroid group (66.7% male, 50.5 +/- 12.6 years) and 57 in the low-dose steroid group (61.4% male, 55.5 +/- 14.2 years). The 60-day mortality was lower in the standard-dose group than in the low-dose group (63.2% vs 48.3%, p=0.04), while 28-day mortality showed no significant difference (50.8% vs 35.4%, p=0.11). After adjusting for confounders, standard-dose steroids reduced 28-day mortality (aHR: 0.339, 95% CI: 0.147- 0.780) and 60-day mortality (aHR: 0.328, 95% CI: 0.152- 0.709), particularly in patients aged < 65 years, non-smokers, those requiring mechanical ventilation, with albumin< 30 g/L, or a PaO2/FiO(2) ratio < 150 mmHg. No differences in co-infections or gastrointestinal bleeding were observed. Conclusion: The standard-dose steroid therapy significantly reduced 28-day and 60-day mortality without major complications in the non-HIV immunocompromised population with severe PCP with ARDS. These findings highlight the potential survival benefit of standard-dose corticosteroid regimen in this population.

Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP). Therefore, we aimed to investigate the correlation between the combined immune and inflammatory indicator: the neutrophil-to-lymphocyte ratio (NLR) and prognosis of non-human immunodeficiency virus (non-HIV) PjP. In the retrospective analysis conducted in ICUs at Beijing Chao-Yang Hospital, we examined data from 157 patients diagnosed with non-HIV PjP. Our findings reveal a concerning hospital mortality rate of 43.3%, with the 28-day mortality rate reaching 47.8%. Through multivariable logistic and Cox regression analyses, we established a significant association between elevated NLR levels and hospital mortality (adjusted odd ratio, 1.025; 95% CI, 1.008-1.043; p = 0.004) or 28-day mortality (adjusted hazard ratio, 1.026; 95% CI, 1.008-1.045; p = 0.005). Specifically, patients with an NLR exceeding 20.3 demonstrated markedly lower overall survival rates, underscoring the biomarker's predictive value for both hospital and 28-day mortality. In conclusion, non-HIV PjP patients in the ICU still have a high rate of mortality and a poor short-term prognosis after discharge. A high level of NLR was associated with an increased risk of hospital mortality and 28-day mortality.

Abstract Objective To verify whether the bleeding risk assessment guidelines from the 9th American College of Chest Physicians (ACCP) are prognostic for respiratory intensive care unit (RICU) patients and to explore risk factors for hemorrhages, we conducted a secondary data analysis based on our previously published cohort study of venous thromboembolism. Patients and methods We performed a secondary data analysis on the single-center prospective cohort from our previous study. Patients admitted to the RICU at Beijing Chao-Yang Hospital from August 1, 2014 to December 31, 2020 were included and followed up until discharge. Results The study enrolled 931 patients, of which 715 (76.8%) were at high risk of bleeding, while the remaining were at low risk. Of the total, 9.2% (86/931) suffered major bleeding, and no significant difference was found between the two risk groups (p = 0.601). High-risk patients had poor outcomes, including higher mortality and longer stays. Independent risk factors for major bleeding were APACHE II score ≥ 15; invasive pulmonary aspergillosis; therapeutic dose of anticoagulants; extracorporeal membrane oxygenation; and continuous renal replacement therapy. Blood transfusion not related to bleeding appeared to be an independent protective factor for major bleeding (OR 0.099, 95% CI 0.045–0.218, p < 0.001). Conclusion Bleeding risk assessment models from the 9th ACCP guidelines may not be suitable for patients in RICU. Building a bleeding risk assessment model that is suitable for patients in all RICUs remains a challenge. Trial registration ClinicalTrials.gov: NCT02213978.

Background Adjuvant corticosteroids are effective in patients with human immunodeficiency virus (HIV)-associated Pneumocystis jirovecii pneumonia (PCP) patients, but the effectiveness of adjuvant corticosteroids in non-HIV PCP remained controversial. This study aimed to evaluate the effects of steroids in non-HIV PCP patients with acute respiratory distress syndrome (ARDS). Methods This retrospective observational study included non-HIV PCP patients with ARDS admitted to the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital from 2015 to 2022 were included. We compared demographics, clinical characteristics, and outcomes between patients who received a 21-day course of standard-dose steroids and those who received low-dose steroids. Kaplan-Meier curve and log-rank test were performed to compare the survival time between standard-dose steroid and low-dose steroid patients. Cox regression analysis was performed to identify risk factors for 28- and 60-day mortality. Results A total of 105 non-HIV PCP with ARDS were identified, 48 in the 21-day course of standard-dose steroid group (66.7% male, 50.5±12.6 years) and 57 in the low-dose steroid group(61.4% male, 55.5±14.2 years). 60-day mortality was significantly different between the two groups (63.2% vs 48.3%, p=0.04), but 28-day mortality was not (50.8% vs 35.4%, p=0.11). After adjustment for confounders, 60-day mortality (adjusted hazard ratio: 0.415, 95% confidence interval: 0.227-0.760) was lower in the 21-day standard-dose steroid group compared with those in the low-dose steroid group. 21-day standard-dose steroids were associated with lower 60-day mortality in patients aged<65 years, no smokers, requiring mechanical ventilation, lactic dehydrogenase≥ 495U/L, and PaO2/FiO2 ratio<150mmHg. There were no differences in co-infections and gastrointestinal bleeding between the two groups. Conclusions In conclusion, the 21-day standard-dose steroids therapy significantly reduced 60-day mortality without major complications in the non-HIV immunocompromised population with severe PCP with ARDS.

IntroductionSystematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS).MethodThis was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument.ResultA total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn’t continue improving after 3 months. Health-related quality of life didn’t change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening.ConclusionThe improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

Abstract Background A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. Methods In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. Results A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). Conclusions Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. Trial Registration ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019.

Background Severe community-acquired pneumonia (S-CAP) is a public health threat, making it essential to identify novel biomarkers and investigate the underlying mechanisms of disease severity. Methods Here, we profiled host responses to S-CAP through proteomics analysis of plasma samples from a cohort of S-CAP patients, non-severe (NS)-CAP patients, diseases controls (DCs), and healthy controls (HCs). Then, typical differentially expressed proteins were then validated by ELISA in an independent cohort. Metabolomics analysis was further performed on both the cohort 1 and cohort 2. Then, the proteomic and metabolomic signatures were compared between the adult and child cohorts to explore the characteristics of severe pneumonia patients. Results There were clear differences between CAP patients and controls, as well as substantial differences between the S-CAP and NS-CAP. Pathway analysis of changes revealed excessive inflammation, suppressed immunity, and lipid metabolic disorders in S-CAP cases. Interestingly, comparing these signatures between the adult and child cohorts confirmed that overactive inflammation and dysregulated lipid metabolism were common features of S-CAP patients, independent of age. The change proportion of glycerophospholipids, glycerolipids, and sphingolipids were obviously different in the adult and child S-CAP cases. Conclusion The plasma multi-omics profiling revealed that excessive inflammation, suppressed humoral immunity, and disordered metabolism are involved in S-CAP pathogenesis.

As the long-term consequences of coronavirus disease 2019 (COVID-19) have not been defined, it is necessary to explore persistent symptoms, long-term respiratory impairment, and impact on quality of life over time in COVID-19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID-19 were followed-up 2 and 3 years after discharge from hospital. Participants completed an in-person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high-resolution computed tomography, and the 6-min walking test. There were 762 patients at the 2-year follow-up and 613 patients at the 3-year follow-up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2-3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3-year follow-up. Persistent radiographic abnormalities, most commonly fibrotic-like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID-19 survivors at 3 years. Further studies are warranted to explore the long-term effects of COVID-19 and develop appropriate rehabilitation strategies.

Objective: To preliminarily analyze the application experience of veno-arterio-venous extracorporeal membrane oxygenation (VAV-ECMO).The VAV-ECMO is a rescue strategy for patients with extremely critical respiratory failure combined with refractory shock. Methods: From February 2016 to February 2022, the characteristics and outcomes of patients who were started on either veno-venous or veno-arterial ECMO due to respiratory or hemodynamic failure, and then converted to VAV-ECMO in respiratory intensive care unit (ICU) of Beijing Chaoyang Hospital were analyzed. Results: A total of 15 patients underwent VAV-ECMO, aged 53 (40, 65) years, and 11 of whom were male. Within the group, VV-ECMO was initially used in 12 patients due to respiratory failure, but then VAV-ECMO was used due to cardiogenic shock (7/12) and septic shock (4/12), while VAV-ECMO was established in two patients due to lung transplantation. One patient was diagnosed with pneumonia complicated by septic shock, which was initially determined to be VA-ECMO, but then switched to VAV-ECMO because it was difficult to maintain oxygenation. The time from the establishment of VV or VA-ECMO to the switch to VAV-ECMO was 3 (1, 5) days and the VAV-ECMO support time was 5 (2, 8) days. ECMO-related complications were bleeding, mostly in the digestive tract (n=4) and airway hemorrhage (n=4), without intracranial hemorrhage, and poor arterial perfusion of the lower limbs (n=2). Among these 15 patients, the overall ICU mortality was 53.3%. The mortality of patients who received VAV-ECMO due to septic shock and cardiogenic shock was 100% (4/4) and 42.8% (3/7), respectively. Two patients who received VAV-ECMO due to lung transplantation all survived. Conclusion: VAV-ECMO may be a safe and effective treatment for carefully selected patients with critical respiratory failure associated with cardiogenic shock or end-stage lung disease lung transplantation transition, however, patients with septic shock may benefit the least.