Nucleic acid 2022


Overlap in pro-inflammatory genes and pathways between COVID-19 and MIS-C



                                                                                                                                                                      In a recent study posted to the medrivix pre-print server, researchers in the United States characterized differential host immune responses in acute coronavirus disease 2019 (COVID-19) and multisysteminflammatory syndrome in children (MIS-C) to inform future development of novel biomarkers for both diseases.

 

Background

To date, COVID-19 and MIS-C, both caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have claimed more lives of children than pediatric mortality from influenza. Both these diseases manifest highly inflammatory states and have distinct signatures of cell injury and cell death, with more heterogeneity and multi-organ involvement observed in MIS-C.

Further, both these diseases show different levels of expression for some genes, including interferon-stimulated gene 15 (ISG15), sialoadhesin (SIGLEC1), and T Cell receptor beta variable 11-2 (TRBV11-2). Previous studies have also shown specific downregulation of T cell-mediated pathways in MIS-C. Furthermore, MIS-C has overlapping clinical symptoms with other inflammatory syndromes, such as Kawasaki disease (KD), making its diagnosis difficult.

About the study

In the present study, researchers collected blood and plasma samples from children at three pediatric hospitals in the United States (US). They stratified all samples by diagnosis, collection time, and disease severity. They used plasma samples for cfRNA and cfDNA profiling using next-generation sequencing (NGS).

Likewise, they performed RNA-seq on wbRNA and compared wbRNA and cfRNA profiles from 96 paired samples in MIS-C and COVID-19. Lastly, they implemented BayesPrism and the Tabula Sapiens human single-cell transcriptome atlas as a reference to quantify cell-types-of-origin (CTO) of the cfRNA. The study cohort comprised 211 children diagnosed with COVID-19 or MIS-C and 26 controls.

Study findings

The researchers identified signatures associated with cellular injury and death that distinguished MIS-C and COVID-19 and the involvement of previously unreported cell types in MIS-C using plasma cfRNA profiling. Plasma cfDNA profiling uncovered the involvement of multiple organs in MIS-C compared to COVID-19 and controls. On the other hand, the wbRNA analysis revealed a substantial overlap in pro-inflammatory pathways between MIS-C and COVID-19. In addition, it revealed pro-inflammatory pathways specific to each disease state. Together, these results provided new insights into the differential pathogenesis of MIS-C and COVID-19 to inform the development of the least invasive diagnostic tests for both acute COVID-19 and MIS-C.

Conclusions

The current large, multi-hospital study of 416 blood samples from 237 patients reported a longitudinal analysis of COVID-19 and MIS-C by deep sequencing of three nucleic acids, cfRNA, wbRNA, and cfDNA. Longitudinal sampling of these cell-associated and cell-free nucleic acids at acute, post-acute, one-month, and three post-hospitalization timepoints enabled a complete view of immune responses and tissue damage associated with MIS-C and COVID-19.

In wbRNA profiling, the researchers observed an opposing dynamics of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS2) in MIS-C and COVID-19. While elevated ADAMTS2 levels returned to baseline in MIS-C at one-month post-hospitalization, the same did not occur in COVID-19 patients. Similarly, killer cell lectin-like receptor subfamily B, member 1 (KLRB1) levels in MIS-C recovered at one-month post-hospitalization but not in COVID-19. Despite the initial severity, most clinical MIS-C symptoms resolved within a few weeks, and inflammatory and injury biomarkers normalized. In cfRNA profiling, most biomarker measurements, such as CTO values, persisted at one month but returned to baseline after three months of hospitalization.

Source: https://4dg2.short.gy/Newsnucleic

Conference name: 6th International Conference on Molecular Biology and Nucleic Acids

Short Name: Nucleic acid 2022

Place: Chicago, USA

Date: August 15-16, 2022

Visit on our Website: https://www.lexismeeting.com/nucleicacids
Whatsapp: +44-7360-516157
Email: nucleicacids@eventqueries.com



Location: United States

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