Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets lipid-producing cells for viral tropism. In this review, we connect systemic lipid couriers, particularly high-density lipoproteins (HDLs) and exosomes, with the neurological facets of SARS-CoV-2 infection. We discuss how SARS-CoV-2 preferentially targets lipid-secreting cells and usurps host cell lipid metabolism for efficient replication and systemic spreading. Besides providing natural veils for viral materials against host immunity, the inherent properties of some of these endogenous lipid particles to traverse the blood–brain barrier (BBB) also offer alternative routes for SARS-CoV-2 neurotropism. Importantly, virus-driven neurological aberrations mediated by HDLs and exosomes are fueled by lipid rafts, which are implicated in the production and transmigration of these lipid particles across the BBB. Finally, we discuss how repurposing existing drugs targeting lipid rafts and cholesterol homeostasis may be beneficial toward alleviating the global coronavirus disease 2019 (COVID-19) disease burden.

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 主要针对产生病毒的脂质细胞。在这篇综述中，我们将全身脂质信使，特别是高密度脂蛋白 (HDL) 和外泌体，与 SARS-CoV-2 感染的神经方面联系起来。我们讨论了 SARS-CoV-2 如何优先靶向脂质分泌细胞并篡夺宿主细胞脂质代谢以实现有效复制和全身传播。除了为病毒物质提供抵抗宿主免疫的天然面纱外，这些内源性脂质颗粒中的一些具有穿越血脑屏障 (BBB) 的固有特性，也为 SARS-CoV-2 的神经趋向性提供了替代途径。重要的是，由 HDL 和外泌体介导的病毒驱动的神经畸变是由脂筏推动的，这与这些脂质颗粒在 BBB 中的产生和迁移有关。最后，我们讨论了重新利用针对脂筏和胆固醇稳态的现有药物如何有助于减轻 2019 年全球冠状病毒病 (COVID-19) 的疾病负担。