Gardinassi Luiz Gustavo, Servian Carolina do Prado, Lima Gesiane da Silva, Dos Anjos Déborah Carolina Carvalho, Gomes Junior Antonio Roberto, Guilarde Adriana Oliveira, Borges Moara Alves Santa Bárbara, Dos Santos Gabriel Franco, Moraes Brenda Grazielli Nogueira, Silva João Marcos Maia, Masson Letícia Carrijo, de Souza Flávia Pereira, da Silva Rodolfo Rodrigues, de Araújo Giovanna Lopes, Rodrigues Marcella Ferreira, da Silva Lidya Cardozo, Meira Sueli, Fiaccadori Fabiola Souza, Souza Menira, Romão Pedro Roosevelt Torres, Spadafora Ferreira Mônica, Coelho Verônica, Chaves Andréa Rodrigues, Simas Rosineide Costa, Vaz Boniek Gontijo, Fonseca Simone Gonçalves
Departamento de Biociências e Tecnologia, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Laboratório de Cromatografia e Espectrometria de Massas, Instituto de Química, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Microbiol Spectr. 2023 Feb 28;11(2):e0219422. doi: 10.1128/spectrum.02194-22.
Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.
2019冠状病毒病(COVID-19)的严重表现和死亡率与生理改变有关,这些生理改变为该疾病的发病机制提供了见解。此外,可以探索促使从COVID-19中恢复的因素,以确定保护的相关因素。细胞代谢是改善重症患者生存的一个潜在靶点,但COVID-19期间代谢与炎症反应之间的关联尚不清楚。我们分析了150例轻至重症患者的血液实验室参数、细胞因子和代谢组,其中33例进展为致命结局。20例患者在出院并从急性疾病中康复后进行了随访。我们使用分层社区网络将代谢组学谱与细胞因子以及炎症、凝血和组织损伤标志物整合起来。严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染会促使血浆代谢组发生显著改变,其活性根据疾病严重程度而变化,并与血氧饱和度相关。死亡背后的差异代谢以氨基酸和相关代谢物(如谷氨酸、谷氨酰-谷氨酸和氧脯氨酸)以及脂质(包括孕酮、磷酸胆碱和溶血磷脂酰胆碱(lysoPCs))为特征。从重症中康复的个体表现出持续的改变,这些改变在嘌呤和磷脂酰肌醇磷酸代谢以及糖酵解方面更为丰富。轻症的康复与维生素E代谢有关。数据整合表明,代谢反应是疾病和康复过程中连接其他生物学特征的枢纽。SARS-CoV-2感染会诱导代谢和炎症反应的协同活动,这取决于疾病严重程度,并共同预测COVID-19的临床结局。COVID-19的特征是具有多样的临床结局,包括无症状到轻度表现或重症疾病及死亡。SARS-CoV-2感染会激活炎症和代谢反应,这些反应会推动保护或病理过程。COVID-19期间炎症和代谢如何相互作用尚不清楚。我们使用高分辨率质谱法研究了COVID-19患者和对照组血浆中的小分子生化化合物(<1500 Da)。年龄、性别和合并症对COVID-19患者的血浆代谢物有深远影响,但我们确定了由疾病严重程度、生存结局和康复情况决定的与氨基酸、脂质、核苷酸和维生素相关的通路和代谢物的显著活性。此外,我们确定了与急性期蛋白和凝血因子相关的代谢物,这些代谢物共同识别出重症患者或死于重症COVID-19的个体。我们的研究表明,可以探索操纵特定的代谢途径来预防过度炎症、器官功能障碍和死亡。