Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19.

Abstract

Rationale: Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. Methods: We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were performed to identify molecules specifically altered in COVID-19-children. We also developed a machine learning-based pipeline named inference of biomolecular combinations with minimal bias (iBM) to prioritize proteins and metabolites strongly altered in COVID-19-children, and experimentally validated the predictions. Results: By comparing to the multi-omic data in adults, we identified 44 proteins and 249 metabolites differentially altered in COVID-19-children against healthy children or COVID-19-adults. Further analyses demonstrated that both deteriorative immune response/inflammation processes and protective antioxidant or anti-inflammatory processes were markedly induced in COVID-19-children. Using iBM, we prioritized two combinations that contained 5 proteins and 5 metabolites, respectively, each exhibiting a total area under curve (AUC) value of 100% to accurately distinguish COVID-19-children from healthy children or COVID-19-adults. Further experiments validated that all the 5 proteins were up-regulated upon coronavirus infection. Interestingly, we found that the prioritized metabolites inhibited the expression of pro-inflammatory factors, and two of them, methylmalonic acid (MMA) and mannitol, also suppressed coronaviral replication, implying a protective role of these metabolites in COVID-19-children. Conclusion: The finding of a strong antagonism of deteriorative and protective effects provided new insights on the mechanism and pathogenesis of COVID-19 in children that mostly underwent mild symptoms. The identified metabolites strongly altered in COVID-19-children could serve as potential therapeutic agents of COVID-19.

• Authors: Chong Wang, Xufang Li, Wanshan Ning, Sitang Gong, Fengxia Yang, Chunxiao Fang, Yu Gong, Di Wu, Muhan Huang, Yujie Gou, Shanshan Fu, Yujie Ren, Ruyi Yang, Yang Qiu, Yu Xue, Yi Xu, Xi Zhou
• Journal: Theranostics (Theranostics) Vol. 11 Issue 16 Pg. 8008-8026 ( 2021) ISSN: 1838-7640 [Electronic] Australia
• PMID: 34335977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Topics

• Adult
• COVID-19 (blood, epidemiology, immunology, virology)
• Child
• Child, Preschool
• China (epidemiology)
• Female
• Hospitalization
• Humans
• Male
• Metabolomics (methods)
• Middle Aged
• Proteomics (methods)
• SARS-CoV-2 (isolation & purification)