The role of cholesterol metabolism in predicting clinical outcome of patients with severe COVID-19

Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway in lethal COVID-19. Last data suggested the possible role of extracellular vesicles and exomeres in COVID-19 pathogenesis. The aim of the present study was to retrospectively evaluate parameters of cholesterol metabolism as possible predictors of fatal outcome of COVID-19. Blood from 39 patients with severe COVID-19 (the main cohort) were collected at the time of admission to the intensive care unit (ICU) (T1) and 7 days after admission to the ICU (T2). After 30 days patients were divided into two subgroups according to outcome-21 non-survivors and 18 survivors. 28 patients (13 non-survivors and 15 survivors) with severe COVID-19 were included as the replication cohort. The study demonstrated that plasma low-and high-density lipoprotein cholesterol levels (LDL-C and HDL-C) were decreased and CCL20/MIP3[a], IL-10, IL-15, IL-27 concentrations were increased in non-survivors compared to controls in T1. STAB1 gene expression was higher in non-survivors than in survivors (p=0.017) in T2. The conjoint fraction of exomeres and LDL particles measured by dynamic light scattering (DLS) was decreased in non-survivors com-pared to survivors in both the main and replication cohorts. We first showed that change of exomeres fraction may be critical in fatal outcome of COVID-19.