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

Abstract

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.

EASIX, Modified EASIX and Simplified EASIX as an Early Predictor for Intensive Care Unit Admission and Mortality in Severe COVID-19 Patients

“…Patients in the high EASIX (≥2.36), high mEASIX (≥704.05) and high sEASIX (≥3.81) groups compared to the “low” groups had significantly lower SpO 2 values, shorter time of use of a non-rebreather mask 10–15 L/min, which resulted from disease progression and the need to intensify the treatment as well as the differences in the values of inflammatory parameters. The results of our analysis, in terms of laboratory parameters, are consistent with the results of studies by other researchers—they correspond to the pathology of the endothelium, which is associated with an intense inflammatory and thrombotic process in patients with severe COVID-19 [ 27 , 28 , 29 , 33 , 34 , 35 ]. Significantly, the modified indices (mEASIX and sEASIX) showed no differences when the “high” and “low” groups were compared with respect to comorbidities, and sEASIX also with respect to gender.…”

“…The high effectiveness of EASIX with regard to the stratification of COVID-19 patients was demonstrated in the study by Garcia et al where, with the use of a retrospective analysis of more than 3000 patients, it was shown that the age-adjusted coefficient (aEASIX-COVID) has an even higher predictive value for mortality. It was also proved that, based on the values of both indices, EASIX and aEASIX, the chances of patient survival rather than death can be assessed more reliably, as illustrated by the significantly higher NPV (negative predictive value) compared to PPV (positive predictive value) [ 29 ]. In other words, with low values of EASIX and aEASIX, there is a greater probability of patient survival than death with high values.…”

“…The values of PPV were also significantly greater than those of NPV, which should be understood as a greater probability of death with high values of the indices than the probability of survival with their low values. This is a somewhat surprising statistic, especially in the context of the publication by Garcia et al, in the case of which the obtained results are completely opposite (NPV higher than PPV) [ 29 ]. The cut-off value obtained in our study, which is significant for the prediction of death in the course of COVID-19 for EASIX (2.36), is greater than the one in the studies conducted by other researchers (Kalicińska et al EASIX ≥ 1.6, Luft et al EASIX ≥ 2.03) [ 27 , 28 ].…”

“…As in the case of haematological diseases, it shows a significant correlation with the concentration of endothelial and inflammatory markers (ANG2, sTM, ST2, CXCL8, CXCL9, IL-18) [ 27 ]. To date, there are only three publications on such an assessment and in each of them statistically significant results were achieved justifying further research in that direction [ 27 , 28 , 29 ].…”

EASIX is an effective marker in predicting mortality of traumatic brain injury patients

“…Researchers found it was associated with levels of endothelial activation markers such as interleukin-18, chemokine-X-C-ligand 8, insulin like-growth-factor-1, suppressor of tumorigenicity-2 [8,9]. Furthermore, the EASIX has been confirmed related with mortality of various patients such as multiple myeloma, COVID-19, diffuse large B-cell lymphoma, small cell lung cancer, sepsis [10][11][12][13][14]. While the prognostic effect of the EASIX has not been testified in TBI patients, we design this study to analyze the relationship between the EASIX and mortality of TBI.…”