Urine-based multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS), a life-threatening condition during critical illness, is a common complication of COVID-19. It can originate from various disease etiologies, including severe infections, major injury, or inhalation of irritants. ARDS poses substantial clinical challenges due to a lack of etiology-specific therapies, multisystem involvement, and heterogeneous, poor patient outcomes. A molecular comparison of ARDS groups holds the potential to reveal common and distinct mechanisms underlying ARDS pathogenesis. METHODS: We performed a comparative analysis of urine-based metabolomics and proteomics profiles from COVID-19 ARDS patients (n = 42) and bacterial sepsis-induced ARDS patients (n = 17). To this end, we used two different approaches, first we compared the molecular omics profiles between ARDS groups, and second, we correlated clinical manifestations within each group with the omics profiles. RESULTS: The comparison of the two ARDS etiologies identified 150 metabolites and 70 proteins that were differentially abundant between the two groups. Based on these findings, we interrogated the interplay of cell adhesion/extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis through a multi-omic network approach. Moreover, we identified a proteomic signature associated with mortality in COVID-19 ARDS patients, which contained several proteins that had previously been implicated in clinical manifestations frequently linked with ARDS pathogenesis. CONCLUSION: In summary, our results provide evidence for significant molecular differences in ARDS patients from different etiologies and a potential synergy of extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis. The proteomic mortality signature should be further investigated in future studies to develop prediction models for COVID-19 patient outcomes.

COVID-19 in Patients with CKD in New York City.

BACKGROUND: COVID-19 has affected millions of people, and several chronic medical conditions appear to increase the risk of severe COVID-19. However, our understanding of COVID-19 outcomes in patients with CKD remains limited. METHODS: This was a retrospective cohort study of patients with and without CKD consecutively admitted with COVID-19 to three affiliated hospitals in New York City. Pre-COVID-19 CKD diagnoses were identified by billing codes and verified by manual chart review. In-hospital mortality was compared between patients with and without underlying CKD. Logistic regression was used to adjust this analysis for confounders and to identify patient characteristics associated with mortality. RESULTS: We identified 280 patients with CKD, and 4098 patients without CKD hospitalized with COVID-19. The median age of the CKD group was 75 (65-84) years, and age of the non-CKD group 62 (48-75) years. Baseline (pre-COVID-19) serum creatinine in patients with CKD was 1.5 (1.2-2.2) mg/dl. In-hospital mortality was 30% in patients with CKD versus 20% in patients without CKD (P<0.001). The risk of in-hospital death in patients with CKD remained higher than in patients without CKD after adjustment for comorbidities (hypertension, diabetes mellitus, asthma, and chronic obstructive pulmonary disease), adjusted OR 1.4 (95% CI,1.1 to 1.9), P=0.01. When stratified by age, elderly patients with CKD (age >70 years) had higher mortality than their age-matched control patients without CKD. In patients with CKD, factors associated with in-hospital mortality were age (adjusted OR, 1.09 [95% CI, 1.06 to 1.12]), P<0.001, baseline and admission serum phosphorus (adjusted OR, 1.5 [95% CI, 1.03 to 2.1], P=0.03 and 1.4 [95% CI, 1.1 to 1.7], P=0.001), serum creatinine on admission >0.3 mg/dl above the baseline (adjusted OR 2.6 [95% CI, 1.2 to 5.4]P=0.01), and diagnosis of acute on chronic kidney injury during hospitalization (adjusted OR 4.6 [95% CI, 2.3 to 8.9], P<0.001). CONCLUSIONS: CKD is an independent risk factor for COVID-19-associated in-hospital mortality in elderly patients. Acute-on-chronic kidney injury increases the odds of in-hospital mortality in patients with CKD hospitalized with COVID-19.