Key points:
- Sequencing technology has revealed biomarker patterns for severe COVID-19 and MIS-C in children.
- MIS-C is hard to diagnose, and researchers still do not know why some children develop the potentially fatal inflammatory disease.
- The team hopes their findings pave the way for diagnostic tests in the future.
Researchers at Children’s National Hospital have identified specific biomarker patterns in the blood that are unique to severe COVID-19 infection, as well as others unique to Multisystem Inflammatory Syndrome in Children (MIS-C), a serious complication of COVID-19 infection in children. These findings pave the way for development of potential diagnostic tests in the future.
The study, published in Cell Reports Medicine, included 416 blood samples from 70 patients with acute COVID-19, and 141 patients with MIS-C across three hospitals: Children's National Hospital, University of California at San Francisco and Emory University/Children's Healthcare of Atlanta. The blood samples were collected at specific times—beginning of the illness, during initial recovery, 1 month after hospitalization and more than 3 months after illness.
The researchers used a combination of both whole blood RNA (wbRNA) sequencing, as well as cell-free RNA (cfRNA) and cell-free DNA (cfDNA) sequencing of plasma samples to identify key biosignatures. Information from wbRNA is primarily from circulating white blood cells and identifies inflammatory and immune responses to infection. In contrast, both cfRNA and cfDNA can inform about the levels and types of cell death from peripheral tissues.
According to the findings, wbRNA analyses revealed that multiple inflammatory pathways are activated in both severe COVID-19 and MIS-C. However, the team noted specific patterns unique to each disease that distinguish them from mild COVID and other control conditions.
Additionally, cfRNA and cfDNA analysis from MIS-C patients demonstrated distinct signatures of cell injury and death, including endothelial cells and a type of neuronal cells called Schwann cells—indicating increased levels of organ injury compared with samples from COVID-19 patients.
“To our knowledge, no one has performed comprehensive analysis of both plasma cell-free RNA and whole blood RNA, as well as cell-free DNA in this setting, which is a powerful approach because it gives us different but complementary types of information,” said Roberta DeBiasi, M.D., principal investigator of the study site at Children’s National and chief of the Division of Pediatric Infectious Diseases.
Over the next few years, the research teams say they will continue working on developing a test that will accurately distinguish MIS-C from other inflammatory conditions affecting children, such as Kawasaki Disease, as well as a test that can predict the likelihood of severe COVID-19 infection.