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病例系列:马拉维若与普伐他汀作为治疗新冠后长期症状/新冠急性后遗症(PASC)的一种治疗选择。

Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC).

作者信息

Patterson Bruce K, Yogendra Ram, Guevara-Coto Jose, Mora-Rodriguez Rodrigo A, Osgood Eric, Bream John, Parikh Purvi, Kreimer Mark, Jeffers Devon, Rutland Cedric, Kaplan Gary, Zgoda Michael

机构信息

IncellDX Inc., San Carlos, CA, United States.

Department of Anesthesiology, Beth Israel Lahey Health, Burlington, MA, United States.

出版信息

Front Med (Lausanne). 2023 Feb 8;10:1122529. doi: 10.3389/fmed.2023.1122529. eCollection 2023.

Abstract

Post-acute sequelae of COVID (PASC), or long COVID, is a multisystem complication of SARS-CoV-2 infection that continues to debilitate millions worldwide thus highlighting the public health importance of identifying effective therapeutics to alleviate this illness. One explanation behind PASC may be attributed to the recent discovery of persistent S1 protein subunit of SARS-CoV-2 in CD16+ monocytes up to 15 months after infection. CD16+ monocytes, which express both CCR5 and fractalkine receptors (CX3CR1), play a role in vascular homeostasis and endothelial immune surveillance. We propose targeting these receptors using the CCR5 antagonist, maraviroc, along with pravastatin, a fractalkine inhibitor, could disrupt the monocytic-endothelial-platelet axis that may be central to the etiology of PASC. Using five validated clinical scales (NYHA, MRC Dyspnea, COMPASS-31, modified Rankin, and Fatigue Severity Score) to measure 18 participants' response to treatment, we observed significant clinical improvement in 6 to 12 weeks on a combination of maraviroc 300 mg per oral twice a day and pravastatin 10 mg per oral daily. Subjective neurological, autonomic, respiratory, cardiac and fatigue symptoms scores all decreased which correlated with statistically significant decreases in vascular markers sCD40L and VEGF. These findings suggest that by interrupting the monocytic-endothelial-platelet axis, maraviroc and pravastatin may restore the immune dysregulation observed in PASC and could be potential therapeutic options. This sets the framework for a future double-blinded, placebo-controlled randomized trial to further investigate the drug efficacy of maraviroc and pravastatin in treating PASC.

摘要

新冠后遗症(PASC),即长期新冠,是一种由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染引发的多系统并发症,它持续困扰着全球数百万人,凸显了寻找有效治疗方法以缓解该疾病的公共卫生重要性。PASC背后的一个原因可能归因于最近的一项发现,即感染后长达15个月,SARS-CoV-2的持续性S1蛋白亚基仍存在于CD16+单核细胞中。表达趋化因子受体5(CCR5)和 fractalkine 受体(CX3CR1)的CD16+单核细胞在血管稳态和内皮免疫监测中发挥作用。我们提出,使用CCR5拮抗剂马拉维罗和fractalkine抑制剂普伐他汀靶向这些受体,可能会破坏单核细胞-内皮-血小板轴,而该轴可能是PASC病因的核心。我们使用五个经过验证的临床量表(纽约心脏协会心功能分级、医学研究委员会呼吸困难量表、COMPASS-31、改良Rankin量表和疲劳严重程度评分)来衡量18名参与者的治疗反应,观察到,每天两次口服300毫克马拉维罗和每天口服10毫克普伐他汀的联合用药在6至12周内带来了显著的临床改善。主观的神经、自主神经、呼吸、心脏和疲劳症状评分均有所下降,这与血管标志物可溶性CD40配体(sCD40L)和血管内皮生长因子(VEGF)的统计学显著下降相关。这些发现表明,通过中断单核细胞-内皮-血小板轴,马拉维罗和普伐他汀可能恢复PASC中观察到的免疫失调,并且可能是潜在的治疗选择。这为未来进一步研究马拉维罗和普伐他汀治疗PASC的药物疗效的双盲、安慰剂对照随机试验奠定了框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/9944830/b22e01ab0b62/fmed-10-1122529-g001.jpg

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