Alterations in the Kynurenine-Tryptophan Pathway and Lipid Dysregulation Are Preserved Features of COVID-19 in Hemodialysis.

Coronavirus disease 2019 (COVID-19)-induced metabolic alterations have been proposed as a source for prognostic biomarkers and may harbor potential for therapeutic exploitation. However, the metabolic impact of COVID-19 in hemodialysis (HD), a setting of profound a priori alterations, remains unstudied. To evaluate potential COVID-19 biomarkers in end-stage kidney disease (CKD G5), we analyzed the plasma metabolites in different COVID-19 stages in patients with or without HD. We recruited 18 and 9 asymptomatic and mild, 11 and 11 moderate, 2 and 13 severely affected, and 10 and 6 uninfected HD and non-HD patients, respectively. Plasma samples were taken at the time of diagnosis and/or upon admission to the hospital and analyzed by targeted metabolomics and cytokine/chemokine profiling. Targeted metabolomics confirmed stage-dependent alterations of the metabolome in non-HD patients with COVID-19, which were less pronounced in HD patients. Elevated kynurenine levels and lipid dysregulation, shown by an increase in circulating free fatty acids and a decrease in lysophospholipids, could distinguish patients with moderate COVID-19 from non-infected individuals in both groups. Kynurenine and lipid alterations were also associated with ICAM-1 and IL-15 levels in HD and non-HD patients. Our findings support the kynurenine pathway and plasma lipids as universal biomarkers of moderate and severe COVID-19 independent of kidney function.

Chronic Inflammation Might Protect Haemodialysis Patients from Severe COVID-19

BACKGROUND AND AIMS Patients on haemodialysis (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and decreased ICU admissions when hospitalized with COVID-19. It was speculated that an altered immune system due to chronic inflammation might protect HD patients from severe COVID-19. Therefore, we designed a study to describe the peripheral blood immune phenotype in HD patients and respective controls with COVID-19. METHOD Sixty-four patients (31 HD, 33 non-HD) with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 16 control patients (10 HD, 6 non-HD) were prospectively included. According to symptoms, COVID-19 patients were categorized as asymptomatic/mild and moderate/severe COVID-19 phenotypes. Cytokine profiling and immune phenotyping were performed. RESULTS Th1 and Th17 plasma cytokine levels were highly increased in HD patients without SARS-CoV-2 infection and were not significantly regulated during COVID-19. In non-HD COVID-19 patients, these cytokines increased significantly with disease severity. While all patients with moderate/severe COVID-19 showed hallmarks of COVID-19 such as decreased CD3+ CD4+ and CD8+ and CD4+CD25hiFoxP3+ regulatory T cells, significantly increased CD38+CD8+ effector memory and CD38+CD8+ TEMRA T cells were detected in HD compared to non-HD patients with moderate/severe COVID-19. Furthermore, CD161+CD8+ T cells decreased significantly in non-HD COVID-19 patients dependent on disease severity, but not in HD patients. Dynamics of B cells and subtypes were comparable in HD and non-HD COVID-19 patients. Significantly fewer moderate/severe COVID-19 HD patients needed ICU treatment [1/13 (7.7%) HD, 12/24 (50%) non-HD], whereas no difference in mortality was observed [4/31 (12.9%) HD, 6/33 non-HD (18.2%)]. CONCLUSION HD patients might be protected from severe COVID-19 due to their chronic inflammatory state with increased CD38+CD8+ effector memory and TEMRA T cells as well as CD161+CD8+ T cells.

COVID-19 In-Hospital Mortality in People with Diabetes Is Driven by Comorbidities and Age-Propensity Score-Matched Analysis of Austrian National Public Health Institute Data.

BACKGROUND: It is a matter of debate whether diabetes alone or its associated comorbidities are responsible for severe COVID-19 outcomes. This study assessed the impact of diabetes on intensive care unit (ICU) admission and in-hospital mortality in hospitalized COVID-19 patients. METHODS: A retrospective analysis was performed on a countrywide cohort of 40,632 COVID-19 patients hospitalized between March 2020 and March 2021. Data were provided by the Austrian data platform. The association of diabetes with outcomes was assessed using unmatched and propensity-score matched (PSM) logistic regression. RESULTS: 12.2% of patients had diabetes, 14.5% were admitted to the ICU, and 16.2% died in the hospital. Unmatched logistic regression analysis showed a significant association of diabetes (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.15-1.34, p < 0.001) with in-hospital mortality, whereas PSM analysis showed no significant association of diabetes with in-hospital mortality (OR: 1.08, 95%CI: 0.97-1.19, p = 0.146). Diabetes was associated with higher odds of ICU admissions in both unmatched (OR: 1.36, 95%CI: 1.25-1.47, p < 0.001) and PSM analysis (OR: 1.15, 95%CI: 1.04-1.28, p = 0.009). CONCLUSIONS: People with diabetes were more likely to be admitted to ICU compared to those without diabetes. However, advanced age and comorbidities rather than diabetes itself were associated with increased in-hospital mortality in COVID-19 patients.