Circulating a-sACE2 correlates with mortality in COVID-19
(A and B) Concentration of a-sACE2 in (A) 82 severe and (B) 45 moderate patients up to 50 days post-symptom onset (PSO). Patients who donated blood more than once are selected here, WHO severity class corresponds to the highest severity level that a patient reached over the whole disease course. Black lines represent median values for the selected patients calculated as a trend over the whole course with five days binning; healthy donors (HD) median sACE2 level over the whole recruitment period is depicted in blue.
(C) Levels of a-sACE2 in healthy donors (151 samples, one sample per donor, no time-based selection performed), COVID-19 patients (717 samples from 295 patients), patients with commonly acquired pneumonia (CAP, 69 samples from 25 patients), and persons with self-reported history of diabetes mellitus and/or myocardial infarction (DM/MI, 91 samples, one sample per donor, NAKO study). WHO severity class is assessed at the time of sampling. Rec denotes recovered COVID-19 patients. For COVID-19 and CAP patients, a mean level within a time frame 10–20 days PSO is depicted. Time frame selection is based on the a-sACE2 level change over the disease course and samples availability, depicted in (A) and (B). Minimum (Min), maximum (Max), and median values by patient/donor group are shown.
(D) Receiver operating characteristic (ROC) curves for predicting death in all patients. Area under curve (AUC) calculated for maximum a-sACE2-concentrations within indicated days post-hospital admission.
(E and F) Cox regression models with two-sided 95% confidence interval for a-sACE2 and IL-6 showing overall survival probability based on maximum marker concentrations within 15 days post-admission (gray area). N = 12 patients in (E) and (F) are chosen independently based on a-sACE2 and IL-6 level and do not represent the same group. Statistical analyses by two-sided Mann–Whitney test (∗∗∗∗p < 0.0001, ∗∗∗p < 0.001, ∗∗p < 0.01, and ∗p < 0.05; ns, not significant). In (A–C), sample mean is calculated from technical duplicates. Boxplots depict median +/− interquartile range. Whisker length is 1.5 interquartile ranges.