Chronic Inflammation Might Protect Hemodialysis Patients From Severe COVID-19

Prietl, Barbara; Odler, Balázs; Kirsch, Alexander H.; Artinger, Katharina; Eigner, Manfred; Schmaldienst, Sabine; Pfeifer, Verena; Stanzer, Stefanie; Eberl, Anita; Raml, Reingard; Pieber, Thomas R.; Rosenkranz, Alexander R.; Brodmann, Marianne; Eller, Philipp; Eller, Kathrin

doi:10.3389/fimmu.2022.821818

Cited by 8 publications

(20 citation statements)

References 47 publications

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“…Some previously published reports showed high mortality rates among maintenance hemodialysis patients hospitalized for SARS-CoV-2 [ 33 – 36 ]. Some other studies demonstrated that chronic inflammation, a salient feature in HD patients, might protect those patients from severe COVID-19-related symptoms, ICU admission, and mortality [ 9 , 16 ]. These discordant results are accepted because of the limitations known in the observational studies and multiple confounders which can affect the patient prognosis like age [ 37 ], associated comorbidities, and selection bias.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of regulatory T cells in SARS-CoV-2 infected hemodialysis patients: relation to clinical and radiological severity

et al. 2022

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Background Disordered Treg counts and function have been observed in patients with SARS-Cov-2 and are thought to contribute to disease severity. In hemodialysis patients, scarce data are available on the Treg response to SARS-CoV-2 or its relation to the clinical presentation. Methods A cross-sectional study included one hundred patients divided into three groups, thirty SARS-CoV-2-infected hemodialysis patients (COV-HD), and thirty confirmed SARSCoV-2 infected patients (COV), and forty non-infected hemodialysis patients (HD). Flow cytometric analysis of CD4, CD25, FoxP3, and CD39+ Tregs was done for all patients and tested for correlation to in-hospital mortality, clinical, radiological severity indices. Results COV-HD and COV patients had significantly lower Treg cell count than HD patients (Median value of 0.016 cell/ μl vs 0.28 cell/ μl, respectively- P: 0.001). COV-HD patients had higher CD39+ Tregs (median value of 0.006 cell/ μl vs 0.002 cell/ μl, respectively- P: 0.04). COV-HD patients had significantly lower hospital stay (median value of 3 vs 13 days, P:0.001), ICU admission rates (26.5% vs 46.7%, P:0.005) and in-hospital mortality (20.7% versus 43.3%, P:0.003) than COV patients. Treg and CD39 expressing Treg counts were not correlated to severity indices in both groups. A high neutrophil to lymphocyte ratio is strongly correlated to disease severity in COV-HD patients. Conclusions This study provides evidence of T-cell, particularly T-regulatory cell decline in SARS-CoV-2 and suggests that hemodialysis per se does not distinctively impact the T-cell response. COV-HD patients exhibited a higher CD39+ Treg count and a better clinical profile, however, larger studies are needed to extrapolate on these findings.

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Section: Discussionmentioning

confidence: 99%

“…( www.ncss.com ). Calculation relied upon a previous study that characterized Tregs in HD patients [ 16 ]. Group sample sizes of 30 and 30 achieve 85% power to reject the null hypothesis of zero effect size when the population effect size is 0.8 and the significance level (alpha) is 0.050 using a two-sided two-sample equal-variance t-test.…”

Section: Methodsmentioning

confidence: 99%

Characterization of regulatory T cells in SARS-CoV-2 infected hemodialysis patients: relation to clinical and radiological severity

et al. 2022

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“…In the present study, GDF-15 emerged as the only biomarker independently associated with poor outcomes in non-dialysis renal patients affected by SARS-CoV-2 infection, out of the other 19 molecules responsive to inflammatory stimuli. Notably, the panel of cytokines, chemokines and uremic toxins that were investigated was built according to the literature review on the more promising biomarkers dysregulated in the course of COVID-19 and/or renal disease [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Growth Differentiation Factor 15 (GDF-15) Levels Associate with Lower Survival in Chronic Kidney Disease Patients with COVID-19

et al. 2022

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A cytokine storm drives the pathogenesis of severe COVID-19 infection and several biomarkers have been linked to mortality. Chronic kidney disease (CKD) emerged as a risk factor for severe COVID-19. We investigated the association between selected biomarkers and mortality in 77 patients hospitalized for COVID-19, and whether they differ in patients with eGFR higher and lower than 45 mL/min. The association between patients’ characteristics, plasma biomarkers and mortality was conducted by univariate logistic regression models and independent predictors of mortality were then used to create a multivariate prediction model through Cox regression. Patients with lower eGFR had a significant increase of GDF-15, CD-25 and RAGE, with higher plasma levels in non-survivors and in patients who needed ventilation. At univariate analysis, low and mid-low GDF-15 quartiles (<4.45 ng/mL) were associated with lower mortality risk, while mid-high and high quartiles (>4.45 ng/mL) were associated with higher mortality risk. Independent association between GDF-15 quartiles and mortality risk was confirmed in the Cox model and adjusted for eGFR, age, fever and dyspnea (HR 2.28, CI 1.53–3.39, p < 0.0001). The strength of the association between GDF-15 quartiles and mortality risk increased in patients with lower compared to higher eGFR (HR 2.53, CI 1.34–4.79 versus HR 1.99, CI 1.17–3.39). Our findings may suggest a further investigation of the effect of GDF-15 signaling pathway inhibition in CKD.

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“…While the use of complex research biomarkers, such as metabolomic analyses ( 12 ) or deep immune phenotyping ( 13 ), is of great interest to understand the pathophysiology of this disease better, especially in vulnerable patient groups, the clinical applicability of such complex biomarkers and scores is currently limited due to lack of availability and high costs. A review of 76 different coring systems, ranging from existing scores to newly developed scores, artificial intelligence algorithms and novel biomarker came to the conclusion that all of these scores have limitations but that the combination of single laboratory parameters may have the greatest potential for implementation ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Validation of a simple risk stratification tool for COVID-19 mortality

et al. 2022

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Risk prediction is an essential part of clinical care, in order to allocate resources and provide care appropriately. During the COVID-19 pandemic risk prediction became a matter of political and public debate as a major clinical need to guide medical and organizational decisions. We previously presented a simplified risk stratification score based on a nomogram developed in Wuhan, China in the early phase of the pandemic. Here we aimed to validate this simplified risk stratification score in a larger patient cohort from one city in Austria. Age, oxygen saturation, C-reactive protein levels and creatinine levels were used to estimate the in-hospital mortality risk for COVID-19 patients in a point based score: 1 point per age decade, 4 points for oxygen saturation <92%, 8 points for CRP > 10 mg/l and 4 points for creatinine > 84 μmol/l. Between June 2020 and March 2021, during the “second wave” of the pandemic, 1,472 patients with SARS-CoV-2 infection were admitted to two hospitals in Graz, Austria. In 961 patients the necessary dataset to calculate the simplified risk stratification score was available. In this cohort, as in the cohort that was used to develop the score, a score above 22 was associated with a significantly higher mortality (p < 0.001). Cox regression confirmed that an increase of one point in the risk stratification score increases the 28-day-mortality risk approximately 1.2-fold. Patients who were categorized as high risk (≥22 points) showed a 3–4 fold increased mortality risk. Our simplified risk stratification score performed well in a separate, larger validation cohort. We therefore propose that our risk stratification score, that contains only two routine laboratory parameter, age and oxygen saturation as variables can be a useful and easy to implement tool for COVID-19 risk stratification and beyond. The clinical usefulness of a risk prediction/stratification tool needs to be assessed prospectively (https://www.cbmed.at/covid-19-risk-calculator/).

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Chronic Inflammation Might Protect Hemodialysis Patients From Severe COVID-19

Cited by 8 publications

References 47 publications

Characterization of regulatory T cells in SARS-CoV-2 infected hemodialysis patients: relation to clinical and radiological severity

Characterization of regulatory T cells in SARS-CoV-2 infected hemodialysis patients: relation to clinical and radiological severity

Growth Differentiation Factor 15 (GDF-15) Levels Associate with Lower Survival in Chronic Kidney Disease Patients with COVID-19

Validation of a simple risk stratification tool for COVID-19 mortality

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