Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19.

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.

A combined immune and inflammatory indicator predict the prognosis of severe Pneumocystis jirovecii pneumonia patients: a 12-year, retrospective, observational cohort.

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.

Two- and 3-year outcomes in convalescent individuals with COVID-19: A prospective cohort study.

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.

Comparison of relapsing polychondritis patients with and without respiratory involvement based on chest computed tomography: a retrospective cohort study.

BACKGROUND: Relapsing polychondritis (RP) patients with tracheal cartilage involvement are different from other patients. The objective of this study was to compare the clinical features and disease patterns between a respiratory involvement subgroup and a non-respiratory involvement subgroup according to chest computed tomography. METHOD: We performed a retrospective cohort study collecting RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 and August 2021. RESULTS: Respiratory involvement affected 59.7% of patients in our cohort. The incidence of costochondritis was more common in RP patients with respiratory involvement (p = 0.03); the incidence of inflammatory eye disease (p = 0.001) and auricular chondritis (p = 0.001) was less frequent in RP respiratory involvement patients.. Compared with the non-respiratory involvement subgroup the incidence of pulmonary infection marginally increased in the respiratory involvement subgroup (p = 0.06). Inflammatory indexes except for C-reactive protein to albumin ratio (CAR) were significantly higher in the respiratory involvement subgroup; analysis revealed no significant relationship between inflammatory indexes and pulmonary infection. CONCLUSION: RP patients with respiratory involvement had a greater incidence of costochondritis and pulmonary infectionand lesser incidence of inflammatory eye diseases and auricular chondritis compared to non-respiratory involvement. Increasing inflammatory indexes suggests that patients with respiratory involvement had a higher disease activity index of RP. The difference in probability of survival was insignificant between subgroups.