PDF(Pubmed)
Abstract：
The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs that suppress virus replication are in clinical use. However, despite strong evidence for the role of virus-induced inflammation in severe COVID-19, no effective anti-inflammatory drug is available to control fatal inflammation as well as efficiently clear the virus. Therefore, there is an urgent need to identify biologically derived immunomodulators that suppress inflammation and promote antiviral immunity. In this study, we evaluated acellular human amniotic fluid (acAF) containing extracellular vesicles (hAF-EVs) as a potential non-toxic and safe biologic for immunomodulation during COVID-19. Our in vitro results showed that acAF significantly reduced inflammatory cytokine production in TLR2/4/7 and SARS-CoV-2 structural protein-stimulated mouse macrophages. Importantly, an intraperitoneal administration of acAF reduced morbidity and mortality in SARS-CoV-2-infected mice. A detailed examination of SARS-CoV-2-infected lungs revealed that the increased protection in acAF-treated mice was associated with reduced viral titers and levels of inflammatory myeloid cell infiltration. Collectively, our results identify a novel biologic that has potential to suppress excessive inflammation and enhance survival following SARS-CoV-2 infection, highlighting the translational potential of acAF against COVID-19.
摘要：
由SARS-CoV-2引起的持续COVID-19大流行与急性呼吸窘迫综合征（ARDS）和致命肺炎有关。SARS-CoV-2引起的过度炎症是ARDS和致命疾病的关键驱动因素。几种FDA批准的抑制病毒复制的药物正在临床使用。然而,尽管有强有力的证据表明病毒诱导的炎症在重症COVID-19中的作用，但目前尚无有效的抗炎药物控制致命性炎症以及有效清除病毒。因此,迫切需要鉴定抑制炎症和促进抗病毒免疫的生物来源的免疫调节剂。在这项研究中,我们评估了含有细胞外囊泡(hAF-EV)的无细胞人羊水(acAF)作为COVID-19期间免疫调节的潜在无毒且安全的生物制剂.我们的体外结果表明，acAF显着降低了TLR2/4/7和SARS-CoV-2结构蛋白刺激的小鼠巨噬细胞中炎症细胞因子的产生。重要的是,腹膜内施用acAF可降低SARS-CoV-2感染小鼠的发病率和死亡率。对SARS-CoV-2感染的肺部的详细检查表明，在acAF治疗的小鼠中，保护作用的增强与病毒滴度的降低和炎性骨髓细胞浸润的水平有关。总的来说，我们的结果确定了一种新的生物制剂，它有可能抑制过度炎症并提高SARS-CoV-2感染后的存活率，突出了acAF对COVID-19的翻译潜力。
