The Systems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, 141 52 Stockholm, Sweden.
Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
Cell Syst. 2022 Aug 17;13(8):665-681.e4. doi: 10.1016/j.cels.2022.06.006. Epub 2022 Jul 8.
The clinical outcome and disease severity in coronavirus disease 2019 (COVID-19) are heterogeneous, and the progression or fatality of the disease cannot be explained by a single factor like age or comorbidities. In this study, we used system-wide network-based system biology analysis using whole blood RNA sequencing, immunophenotyping by flow cytometry, plasma metabolomics, and single-cell-type metabolomics of monocytes to identify the potential determinants of COVID-19 severity at personalized and group levels. Digital cell quantification and immunophenotyping of the mononuclear phagocytes indicated a substantial role in coordinating the immune cells that mediate COVID-19 severity. Stratum-specific and personalized genome-scale metabolic modeling indicated monocarboxylate transporter family genes (e.g., SLC16A6), nucleoside transporter genes (e.g., SLC29A1), and metabolites such as α-ketoglutarate, succinate, malate, and butyrate could play a crucial role in COVID-19 severity. Metabolic perturbations targeting the central metabolic pathway (TCA cycle) can be an alternate treatment strategy in severe COVID-19.
新型冠状病毒疾病 2019（COVID-19）的临床结果和疾病严重程度存在异质性，疾病的进展或死亡率不能仅用年龄或合并症等单一因素来解释。在这项研究中，我们使用基于系统的全血 RNA 测序、流式细胞术免疫表型分析、血浆代谢组学和单核细胞单细胞代谢组学的系统生物学分析，从个体和群体水平识别 COVID-19 严重程度的潜在决定因素。单核吞噬细胞的数字细胞定量和免疫表型分析表明，其在协调介导 COVID-19 严重程度的免疫细胞方面发挥了重要作用。分层特异性和个性化基因组规模代谢建模表明，单羧酸转运蛋白家族基因（例如 SLC16A6）、核苷转运蛋白基因（例如 SLC29A1）以及代谢物（例如 α-酮戊二酸、琥珀酸、苹果酸和丁酸盐）可能在 COVID-19 严重程度中发挥关键作用。针对中心代谢途径（三羧酸循环）的代谢扰动可能是严重 COVID-19 的另一种治疗策略。
