Coronavirus disease 2019 (COVID-19) has gained prominence as a global pandemic. Studies have suggested that systemic alterations persist in a considerable proportion of COVID-19 patients after hospital discharge. We used proteomic and metabolomic approaches to analyze plasma samples obtained from 30 healthy subjects and 54 COVID-19 survivors 6 months after discharge from the hospital, including 30 non-severe and 24 severe patients. Through this analysis, we identified 1019 proteins and 1091 metabolites. The differentially expressed proteins and metabolites were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Among the patients evaluated, 41% of COVID-19 survivors reported at least one clinical symptom and 26.5% showed lung imaging abnormalities at 6 months after discharge. Plasma proteomics and metabolomics analysis showed that COVID-19 survivors differed from healthy control subjects in terms of the extracellular matrix, immune response, and hemostasis pathways. COVID-19 survivors also exhibited abnormal lipid metabolism, disordered immune response, and changes in pulmonary fibrosis-related proteins. COVID-19 survivors show persistent proteomic and metabolomic abnormalities 6 months after discharge from the hospital. Hence, the recovery period for COVID-19 survivors may be longer.

BackgroundHuman infections with the H7N9 virus could lead to lung damage and even multiple organ failure, which is closely associated with a high mortality rate. However, the metabolic basis of such systemic alterations remains unknown.MethodsThis study included hospitalized patients (n = 4) with laboratory-confirmed H7N9 infection, healthy controls (n = 9), and two disease control groups comprising patients with pneumonia (n = 9) and patients with pneumonia who received steroid treatment (n = 10). One H7N9-infected patient underwent lung biopsy for histopathological analysis and expression analysis of genes associated with lung homeostasis. H7N9-induced systemic alterations were investigated using metabolomic analysis of sera collected from the four patients by using ultra-performance liquid chromatography-mass spectrometry. Chest digital radiography and laboratory tests were also conducted.FindingsTwo of the four patients did not survive the clinical treatments with antiviral medication, steroids, and oxygen therapy. Biopsy revealed disrupted expression of genes associated with lung epithelial integrity. Histopathological analysis demonstrated severe lung inflammation after H7N9 infection. Metabolomic analysis indicated that fatty acid metabolism may be inhibited during H7N9 infection. Serum levels of palmitic acid, erucic acid, and phytal may negatively correlate with the extent of lung inflammation after H7N9 infection. The changes in fatty acid levels may not be due to steroid treatment or pneumonia.InterpretationAltered structural and secretory properties of the lung epithelium may be associated with the severity of H7N9-infection-induced lung disease. Moreover, fatty acid metabolism level may predict a fatal outcome after H7N9 virus infection.

Background: Hyperphosphatemia is a common complication of late-stage chronic kidney disease (CKD). Nicotinamide (NAM) has been reported as an adjunctive therapy for hyperphosphatasemia, but the effect of NAM on fibroblast growth factor 23 (FGF23) and Klotho has rarely been reported. Methods:We randomly assigned 98 patients who underwent regular hemodialysis to received NAM (0.5-1.5 g per day, or 1-3 tablets per day) or placebo (1-3 tablets per day) as an add-on therapy of calcium-based phosphorus binders in a 1:1 ratio. All enrollments were followed-up for 52 weeks. We investigated the serum phosphorus as the primary outcome and serum FGF23 and Klotho as the secondary outcomes. Abdominal aortic calcification (AAC), which had a good correlation with coronary calcification was also compared between the two groups.Results: In total, 37 patients in the placebo group and 35 patients in the NAM group completed the 52-week follow-up. Compared with the placebo group, the NAM group showed a significant decrease of serum phosphorus at the 8 th , 12 th , 20 th , 44 th , and 52 nd week. There was a declining trend of FGF23 and Klotho in both the placebo and NAM groups. Linear mixed models (LMMs) for overall comparisons by repeated measures of analysis of variance (ANOVA) revealed a significant decrease of FGF23 and slower declining rate of Klotho in the NAM group. No significant difference of AAC was detected between the two groups (P=0.805).Conclusions: NAM can not only further decrease the phosphorus level but also reduce the FGF23 level and slow down the descending rate of Klotho in chronic hemodialysis patients.

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