Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre «Kurchatov Institute», Gatchina, Russia.
Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russia.
PLoS One. 2023 Feb 9;18(2):e0278083. doi: 10.1371/journal.pone.0278083. eCollection 2023.
Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway in lethal COVID-19 caused by SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2). Last data suggested the possible role of extracellular vesicles in COVID-19 pathogenesis. The aim of the present study was to retrospectively evaluate parameters of cholesterol metabolism and newly identified EVs, exomeres, as possible predictors of fatal outcome of COVID-19 patients infected by the Alpha and the Delta variants of SARS-CoV-2 virus. Blood from 67 patients with severe COVID-19 were collected at the time of admission to the intensive care unit (ICU) and 7 days after admission to the ICU. After 30 days patients were divided into two subgroups according to outcome-34 non-survivors and 33 survivors. This study demonstrated that plasma low- and high-density lipoprotein cholesterol levels (LDL-C and HDL-C) were decreased in non-survivors compared to controls at the time of admission to the ICU. The conjoint fraction of exomeres and LDL particles measured by dynamic light scattering (DLS) was decreased in non-survivors infected by the Alpha and the Delta variants compared to survivors at the time of admission to the ICU. We first showed that reduction of exomeres fraction may be critical in fatal outcome of COVID-19.
我们之前进行的转录组分析显示，在由 SARS-CoV-2 病毒（严重急性呼吸综合征冠状病毒 2）引起的致死性 COVID-19 中，参与低密度脂蛋白颗粒受体 (LDLR) 活性途径的基因上调。最新数据表明，细胞外囊泡可能在 COVID-19 发病机制中发挥作用。本研究的目的是回顾性评估胆固醇代谢参数和新发现的 EVs（外切体）作为 SARS-CoV-2 病毒的 Alpha 和 Delta 变体感染 COVID-19 患者致命结局的可能预测因子。在入住重症监护病房 (ICU) 时和入住 ICU 后 7 天，采集了 67 名重症 COVID-19 患者的血液。30 天后，根据患者的预后将患者分为两组-34 名非幸存者和 33 名幸存者。本研究表明，与对照组相比，入住 ICU 时非幸存者的血浆低和高密度脂蛋白胆固醇水平（LDL-C 和 HDL-C）降低。与幸存者相比，入住 ICU 时感染 Alpha 和 Delta 变体的非幸存者的外切体和 LDL 颗粒的联合分数（通过动态光散射 (DLS) 测量）降低。我们首次表明，外切体分数的降低可能是 COVID-19 致命结局的关键。
