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

Pérez-García, Felipe; Bailén, Rebeca; Torres-Macho, Juan; Fernández-Rodríguez, Amanda; Jiménez-Sousa, Maria Ángeles; Jiménez, Eva; Pérez-Butragueño, Mario; Cuadros-González, Juan; Cadiñanos, Julen; García-García, Irene; Jiménez-González, María; Ryan, Pablo; Resino, Salvador

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 log(2)-transformed for analysis. Results: Log(2)-EASIX and log(2)-aEASIX-COVID were independently associated with an increased risk of death in both cohorts (p < 0.001). Log(2)-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 log(2)-EASIX (p < 0.001). For log(2) 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 log(2) aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log(2) 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.