EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

Luft, Thomas; Wendtner, Clemens‐Martin; Kosely, Florentina; Radujkovic, Aleksandar; Benner, Axel; Korell, Felix; Kihm, Lars; Bauer, Matthias; Dreger, Peter; Merle, Uta

doi:10.3389/fimmu.2021.634416

Cited by 22 publications

(17 citation statements)

References 53 publications

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“…On the other hand, IL-33 increased moderately in critically ill COVID-19 patients but did not change in deceased ones [28]. Serum sST2 also associated to worse outcomes (severity and death) in a cohort of 100 patients hospitalized for COVID-19 being evaluated for endothelial activation and stress [29]. Our study also analyzed secondary outcomes such as need for additional therapy or oxygen/ventilatory support.…”

Section: Discussionmentioning

confidence: 90%

Early Measurement of Blood sST2 Is a Good Predictor of Death and Poor Outcomes in Patients Admitted for COVID-19 Infection

Sánchez‐Marteles

Rubio-Gracia

Peña-Fresneda

et al. 2021

JCM

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Although several biomarkers have shown correlation to prognosis in COVID-19 patients, their clinical value is limited because of lack of specificity, suboptimal sensibility or poor dynamic behavior. We hypothesized that circulating soluble ST2 (sST2) could be associated to a worse outcome in COVID-19. In total, 152 patients admitted for confirmed COVID-19 were included in a prospective non-interventional, observational study. Blood samples were drawn at admission, 48–72 h later and at discharge. sST2 concentrations and routine blood laboratory were analyzed. Primary endpoints were admission at intensive care unit (ICU) and mortality. Median age was 57.5 years [Standard Deviation (SD: 12.8)], 60.4% males. 10% of patients (n = 15) were derived to ICU and/or died during admission. Median (IQR) sST2 serum concentration (ng/mL) rose to 53.1 (30.9) at admission, peaked at 48–72 h (79.5(64)) and returned to admission levels at discharge (44.9[36.7]). A concentration of sST2 above 58.9 ng/mL was identified patients progressing to ICU admission or death. Results remained significant after multivariable analysis. The area under the receiver operating characteristics curve (AUC) of sST2 for endpoints was 0.776 (p = 0.001). In patients admitted for COVID-19 infection, early measurement of sST2 was able to identify patients at risk of severe complications or death.

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Section: Discussionmentioning

confidence: 90%

Early Measurement of Blood sST2 Is a Good Predictor of Death and Poor Outcomes in Patients Admitted for COVID-19 Infection

Sánchez‐Marteles

Rubio-Gracia

Peña-Fresneda

et al. 2021

JCM

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“…Widespread endotheliitis and coagulopathy are also keys in the pathophysiology of COVID-19 ( 1 ). Recently, Luft et al ( 22 ) have reported in two cohorts of 100 and 126 patients that EASIX predicts COVID19 outcome and may discriminate patients who need intensive surveillance. Besides, high EASIX values correlated with increased serum values of endothelial (angiopoietin-2, CXCL8, soluble thrombomodulin, and suppressor of tumorigenicity-2) and inflammatory (CXCL9, IL18, and IL18BPa) biomarkers ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Luft et al ( 22 ) have reported in two cohorts of 100 and 126 patients that EASIX predicts COVID19 outcome and may discriminate patients who need intensive surveillance. Besides, high EASIX values correlated with increased serum values of endothelial (angiopoietin-2, CXCL8, soluble thrombomodulin, and suppressor of tumorigenicity-2) and inflammatory (CXCL9, IL18, and IL18BPa) biomarkers ( 22 ). In our study, EASIX showed reasonable accuracy in predicting death within 28 days in hospitalized COVID-19 patients despite its simplicity and the fact that it was developed in a different setting.…”

Section: Discussionmentioning

confidence: 99%

Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019

et al. 2021

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Background: Endothelial Activation and Stress Index (EASIX) predict death in patients undergoing allogeneic hematopoietic stem cell transplantation who develop endothelial complications. Because coronavirus disease 2019 (COVID-19) patients also have coagulopathy and endotheliitis, we aimed to assess whether EASIX predicts death within 28 days in hospitalized COVID-19 patients.Methods: We performed a retrospective study on COVID-19 patients from two different cohorts [derivation (n = 1,200 patients) and validation (n = 1,830 patients)]. The endpoint was death within 28 days. The main factors were EASIX [(lactate dehydrogenase * creatinine)/thrombocytes] and aEASIX-COVID (EASIX * age), which were log2-transformed for analysis.Results: Log2-EASIX and log2-aEASIX-COVID were independently associated with an increased risk of death in both cohorts (p < 0.001). Log2-aEASIX-COVID showed a good predictive performance for 28-day mortality both in the derivation cohort (area under the receiver-operating characteristic = 0.827) and in the validation cohort (area under the receiver-operating characteristic = 0.820), with better predictive performance than log2-EASIX (p < 0.001). For log2 aEASIX-COVID, patients with low/moderate risk (<6) had a 28-day mortality probability of 5.3% [95% confidence interval (95% CI) = 4–6.5%], high (6–7) of 17.2% (95% CI = 14.7–19.6%), and very high (>7) of 47.6% (95% CI = 44.2–50.9%). The cutoff of log2 aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log2 aEASIX-COVID = 7 showed a positive predictive value of 47.6% and negative predictive value of 89.8%.Conclusion: Both EASIX and aEASIX-COVID were associated with death within 28 days in hospitalized COVID-19 patients. However, aEASIX-COVID had significantly better predictive performance than EASIX, particularly for discarding death. Thus, aEASIX-COVID could be a reliable predictor of death that could help to manage COVID-19 patients.

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“…Plus, multiple investigations found elevated levels of NLRP3 independent IL-18 processing enzymes, particularly granzyme B and proteinase 3, suggesting roles of other inflammatory mechanisms in SARS-CoV-2-induced production of IL-18 [ 140 , 141 ]. Second, several studies documented significantly increased levels of the IL-18BP alongside the IL-18 in COVID-19 patients [ 136 , 142 , 143 ]. However, it seems that enhanced production of IL-18BP in response to IFN-γ and other stimulators is insufficient for inhibiting the IL-18–IFN-γ axis, leading to immune dysregulation, particularly during the final stages of the disease.…”

Section: Il-18 and Covid-19mentioning

confidence: 99%

The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19

et al. 2022

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A global pandemic has erupted as a result of the new brand coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has been consociated with widespread mortality worldwide. The antiviral immune response is an imperative factor in confronting the recent coronavirus disease 2019 (COVID-19) infections. Meantime, cytokines recognize as crucial components in guiding the appropriate immune pathways in the restraining and eradication of the virus. Moreover, SARS-CoV-2 can induce uncontrolled inflammatory responses characterized by hyper-inflammatory cytokine production, which causes cytokine storm and acute respiratory distress syndrome (ARDS). As excessive inflammatory responses are contributed to the severe stage of the COVID-19 disease, therefore, the pro-inflammatory cytokines are regarded as the Achilles heel during COVID-19 infection. Among these cytokines, interleukin (IL-) 1 family cytokines (IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38) appear to have a strong inflammatory role in severe COVID-19. Hence, understanding the underlying inflammatory mechanism of these cytokines during infection is critical for reducing the symptoms and severity of the disease. Here, the possible mechanisms and pathways involved in inflammatory immune responses are discussed.

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EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

Cited by 22 publications

References 53 publications

Early Measurement of Blood sST2 Is a Good Predictor of Death and Poor Outcomes in Patients Admitted for COVID-19 Infection

Early Measurement of Blood sST2 Is a Good Predictor of Death and Poor Outcomes in Patients Admitted for COVID-19 Infection

Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019

The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19

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