Post-acute sequelae of SARS-CoV-2 cardiovascular symptoms are associated with trace-level cytokines that affect cardiomyocyte function

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL ACS Medicinal Chemistry Letters Pub Date : 2024-10-30 DOI:10.1038/s41564-024-01838-z

Jane E. Sinclair, Courtney Vedelago, Feargal J. Ryan, Meagan Carney, Meredith A. Redd, Miriam A. Lynn, Branka Grubor-Bauk, Yuanzhao Cao, Anjali K. Henders, Keng Yih Chew, Deborah Gilroy, Kim Greaves, Larisa Labzin, Laura Ziser, Katharina Ronacher, Leanne M. Wallace, Yiwen Zhang, Kyle Macauslane, Daniel J. Ellis, Sudha Rao, Lucy Burr, Amanda Bain, Anjana Karawita, Benjamin L. Schulz, Junrong Li, David J. Lynn, Nathan Palpant, Alain Wuethrich, Matt Trau, Kirsty R. Short

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Abstract

An estimated 65 million people globally suffer from post-acute sequelae of COVID-19 (PASC), with many experiencing cardiovascular symptoms (PASC-CVS) like chest pain and heart palpitations. This study examines the role of chronic inflammation in PASC-CVS, particularly in individuals with symptoms persisting over a year after infection. Blood samples from three groups—recovered individuals, those with prolonged PASC-CVS and SARS-CoV-2-negative individuals—revealed that those with PASC-CVS had a blood signature linked to inflammation. Trace-level pro-inflammatory cytokines were detected in the plasma from donors with PASC-CVS 18 months post infection using nanotechnology. Importantly, these trace-level cytokines affected the function of primary human cardiomyocytes. Plasma proteomics also demonstrated higher levels of complement and coagulation proteins in the plasma from patients with PASC-CVS. This study highlights chronic inflammation’s role in the symptoms of PASC-CVS.

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SARS-CoV-2 急性后遗症的心血管症状与影响心肌细胞功能的痕量细胞因子有关

据估计，全球有 6500 万人患有 COVID-19 急性后遗症（PASC），其中许多人都有胸痛和心悸等心血管症状（PASC-CVS）。本研究探讨了慢性炎症在 PASC-CVS 中的作用，尤其是在感染后症状持续一年以上的人群中。从三组人（康复者、PASC-CVS 患者和 SARS-CoV-2 阴性患者）的血液样本中发现，PASC-CVS 患者的血液特征与炎症有关。利用纳米技术在感染后 18 个月的 PASC-CVS 献血者血浆中检测到了痕量水平的促炎细胞因子。重要的是，这些痕量级细胞因子会影响原代人类心肌细胞的功能。血浆蛋白质组学还显示，PASC-CVS 患者血浆中的补体和凝血蛋白水平较高。这项研究强调了慢性炎症在 PASC-CVS 症状中的作用。

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.

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