Plasma membrane cholesterol is required for proper trafficking and localization of receptors that facilitate severe acute respiratory syndrome coronavirus 2 infection. High-density lipoproteins (HDL) mobilize plasma membrane cholesterol, and HDL-cholesterol levels are associated with the severity of COVID-19 disease and mortality. However, HDL-cholesterol levels poorly reflect the function of this complex family of particles, and a detailed assessment of COVID-19-associated changes in HDL functionality and its prognostic value is lacking. In the present study, we assessed HDL cholesterol efflux capacity, HDL anti-inflammatory and antioxidant properties, and changes in HDL composition and metabolism in COVID-19 (n = 48) and non-COVID pneumonia patients (n = 32). COVID-19 infection markedly reduced the activity of lecithin-cholesteryl-acyltransferase and functional parameters of HDL, such as the cholesterol efflux capacity, arylesterase activity of paraoxonase 1, and anti-oxidative capacity of apoB-depleted serum when compared to non-COVID pneumonia at baseline, paralleled by markedly reduced levels of HDL-cholesterol. Of particular interest, low HDL cholesterol efflux capacity was associated with increased mortality risk in COVID-19 patients, independent of HDL-C levels. Our results highlight profound effects of COVID-19 infection on HDL function, metabolism, and composition. Low HDL cholesterol efflux capacity indicates a fatal course of COVID-19, independent of HDL-cholesterol levels.

中文翻译：

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低 HDL 胆固醇流出能力表明 COVID-19 的致命过程

促进严重急性呼吸系统综合症冠状病毒 2 感染的受体的正确运输和定位需要质膜胆固醇。高密度脂蛋白 (HDL) 可动员质膜胆固醇，而 HDL 胆固醇水平与 COVID-19 疾病的严重程度和死亡率有关。然而，HDL 胆固醇水平不能很好地反映这一复杂粒子家族的功能，并且缺乏对 COVID-19 相关 HDL 功能变化及其预后价值的详细评估。在本研究中，我们评估了 COVID-19（n = 48）和非 COVID 肺炎患者（n= 32）。与非 COVID 肺炎相比，COVID-19 感染显着降低了卵磷脂-胆固醇-酰基转移酶的活性和 HDL 的功能参数，例如胆固醇流出能力、对氧磷酶 1 的芳基酯酶活性和去除 apoB 的血清的抗氧化能力在基线时，HDL-胆固醇水平显着降低。特别有趣的是，低 HDL 胆固醇流出能力与 COVID-19 患者死亡风险增加相关，与 HDL-C 水平无关。我们的结果突出了 COVID-19 感染对 HDL 功能、代谢和组成的深远影响。低 HDL 胆固醇流出能力表明 COVID-19 的致命过程，与 HDL 胆固醇水平无关。