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Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors.

ABSTRACT: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a rapid response by the scientific community to further understand and combat its associated pathologic etiology. A focal point has been on the immune responses mounted during the acute and post-acute phases of infection, but the immediate post-diagnosis phase remains relatively understudied. We sought to better understand the immediate post-diagnosis phase by collecting blood from study participants soon after a positive test and identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14^-CD16⁺ and intermediate CD14⁺CD16⁺ monocytes. Additionally, in the lymphocyte compartment, CD8⁺ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. Importantly, the identification of these cellular and molecular immune changes occurred at the early stages of COVID-19 disease. These observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19.

SUBMITTER: Drake KA

PROVIDER: S-EPMC10246026 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors.

Drake Katherine A KA Talantov Dimitri D Tong Gary J GJ Lin Jack T JT Verheijden Simon S Katz Samuel S Leung Jacqueline M JM Yuen Benjamin B Krishna Vinod V Wu Michelle J MJ Sutherland Alex A Short Sarah A SA Kheradpour Pouya P Mumbach Maxwell M Franz Kate K Trifonov Vladimir V Lucas Molly V MV Merson James J Kim Charles C CC

bioRxiv : the preprint server for biology 20230526

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a rapid response by the scientific community to further understand and combat its associated pathologic etiology. A focal point has been on the immune responses mounted during the acute and post-acute phases of infection, but the immediate post-diagnosis phase remains relatively understudied. We sought to better understand the immediate post-diagnosis phase by collecting blood from study participan ...[more]

PMID: 37292797

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Project description: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.

Project description:BackgroundEndometrial cancer (EC) is one of the most common gynecological cancers. The traditional diagnosis of EC relies on histopathology, which, however, is invasive and may arouse tumor spread. There have been many studies aiming to find the metabolomic biomarkers of EC to improve the early diagnosis of cancer in a non-invasive or minimally invasive way, which can also provide valuable information for understanding the disease. However, most of these studies only analyze a single type of sample by metabolomics, and cannot provide a comprehensive view of the altered metabolism in EC patients. Our study tries to gain a pathway-based view of multiple types of samples for understanding metabolomic disorders in EC by combining metabolomics and proteomics.MethodsForty-four EC patients and forty-three controls were recruited for the research. We collected endometrial tissue, urine, and intrauterine brushing samples. Untargeted metabolomics and untargeted proteomics were both performed on the endometrial tissue samples, while only untargeted metabolomics was performed on the urine and intrauterine brushing samples.ResultsBy integrating the differential metabolites and proteins between EC patients and controls detected in the endometrial tissue samples, we identified several EC-related significant pathways, such as amino acid metabolism and nucleotide metabolism. The significance of these pathways and the potential of metabolite biomarker-based diagnosis were then further verified by using urine and intrauterine brushing samples. It was found that the regulation of metabolites involved in the significant pathways showed similar trends in the intrauterine brushings and the endometrial tissue samples, while opposite trends in the urine and the endometrial tissue samples.ConclusionsWith multi-omics characterization of multi-biosamples, the metabolomic changes related to EC are illustrated in a pathway-based way. The network of altered metabolites and related proteins provides a comprehensive view of altered metabolism in the endometrial tissue samples. The verification of these critical pathways by using urine and intrauterine brushing samples provides evidence for the possible non-invasive or minimally invasive biopsy for EC diagnosis in the future.

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Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors.

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Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors.

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