BACKGROUND: Community-acquired pneumonia (CAP) represents a significant public health concern due to its widespread prevalence and substantial healthcare costs. This study was to utilize an integrated proteomic and metabolomic approach to explore the mechanisms involved in severe CAP. METHODS: We integrated proteomics and metabolomics data to identify potential biomarkers for early diagnosis of severe CAP. Plasma samples were collected from 46 CAP patients (including 27 with severe CAP and 19 with non-severe CAP) and 19 healthy controls upon admission. A comprehensive analysis of the combined proteomics and metabolomics data was then performed to elucidate the key pathological features associated with CAP severity. RESULTS: The proteomic and metabolic signature was markedly different between CAPs and healthy controls. Pathway analysis of changes revealed complement and coagulation cascades, ribosome, tumor necrosis factor (TNF) signaling pathway and lipid metabolic process as contributors to CAP. Furthermore, alterations in lipid metabolism, including sphingolipids and phosphatidylcholines (PCs), and dysregulation of cadherin binding were observed, potentially contributing to the development of severe CAP. Specifically, within the severe CAP group, sphingosine-1-phosphate (S1P) and apolipoproteins (APOC1 and APOA2) levels were downregulated, while S100P level was significantly upregulated. CONCLUSION: The combined proteomic and metabolomic analysis may elucidate the complexity of CAP severity and inform the development of improved diagnostic tools.

Objective To measure the reads numbers of Human Herpes Virus in blood sample from patients with sepsis by using Next Generation sequencing (NGS) and explore the relationship between read number of virus and the severity, prognosis, immune status of septic patients.Methods Blood sample and clinical information from 150 patients with sepsis were enrolled in this study. All patients' blood samples were sent to perform NGS pathogenic test. According to the results of NGS, septic patients were divided into HHV-detected group and HHV-undetected group. Besides, patients were scored with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ ) on the day of blood collection. The counts of total leukocytes, lymphocytes and the levels of cytokines were also measured. Results 51.3 percent of septic patients were detected with HHV nucleic acid. The APACHE Ⅱ and SOFA scores were significantly higher in HHV-detected patients compared with patients in HHV-undetected group. Besides, patients who had a higher SOFA score might lead to a higher detection rate of HHV. Moreover, the 28-day and 90-day mortality rates were higher in detected group (P< 0.01). The detection of HHV nucleic acid was positively correlated with a high 90-day mortality rate (P= 0.0056). One-way analysis of variance revealed that the counts of total lymphocyte and different types of lymphocyte (CD19+B、CD4+T、CD8+T、CD56+ lymphocyte) were significantly less in detected group than that in undetected group. Furthermore, both the levels of pro-inflammatory cytokines (TNF-α、IL-2R、IL-6、IL-8) and anti-inflammatory cytokines (IL-10) in detected group were significantly higher than those in undetected group. Gender, age, APACHE Ⅱ , SOFA, IL-2R, IL-10, CD19+B lymphocyte and T cells, were still significant even after multivariate logistic analyses. Conclusions The detection rate of HHV nucleic acid in patients with sepsis was high. The detection of HHV was a high-risk factor of death in patients with sepsis. The cut-off value which is more than 100 had a significant clinical value. The infection of HHV could be conducted by dysfunction of immunity.