Plasma cell-free RNA characteristics in COVID-19 patients

Abstract

The pathogenesis of COVID-19 is still elusive, which impedes disease progression prediction, differential diagnosis, and targeted therapy. Plasma cell-free RNAs (cfRNAs) carry unique information from human tissue and thus could point to resourceful solutions for pathogenesis and host-pathogen interactions. Here, we performed a comparative analysis of cfRNA profiles between COVID-19 patients and healthy donors using serial plasma. Analyses of the cfRNA landscape, potential gene regulatory mechanisms, dynamic changes in tRNA pools upon infection, and microbial communities were performed. A total of 380 cfRNA molecules were up-regulated in all COVID-19 patients, of which seven could serve as potential biomarkers (AUC > 0.85) with great sensitivity and specificity. Antiviral (NFKB1A, IFITM3, and IFI27) and neutrophil activation (S100A8, CD68, and CD63)–related genes exhibited decreased expression levels during treatment in COVID-19 patients, which is in accordance with the dynamically enhanced inflammatory response in COVID-19 patients. Noncoding RNAs, including some microRNAs (let 7 family) and long noncoding RNAs (GJA9-MYCBP) targeting interleukin (IL6/IL6R), were differentially expressed between COVID-19 patients and healthy donors, which accounts for the potential core mechanism of cytokine storm syndromes; the tRNA pools change significantly between the COVID-19 and healthy group, leading to the accumulation of SARS-CoV-2 biased codons, which facilitate SARS-CoV-2 replication. Finally, several pneumonia-related microorganisms were detected in the plasma of COVID-19 patients, raising the possibility of simultaneously monitoring immune response regulation and microbial communities using cfRNA analysis. This study fills the knowledge gap in the plasma cfRNA landscape of COVID-19 patients and offers insight into the potential mechanisms of cfRNAs to explain COVID-19 pathogenesis.

WITHDRAWN: Nucleic acid biomarkers of immune response and cell and tissue damage in COVID-19 and MIS-C

“…In contrast, plasma cfRNA and cfDNA both measure levels and types of cell death from circulating cell types and peripheral tissues 17,39 . With respect to cells that are turning over or dying, cfDNA enables precise quantification of cell numbers, whereas cfRNA enables characterization of gene expression and pathways [40][41][42] . cfRNA profiling can leverage the extensive information regarding cell type specific gene expression that is available from recent large-scale human cell atlas projects, whereas reference data for cfDNA methylation profiling is currently more limited 17 .…”

SARS-CoV-2 impacts the transcriptome and epigenome at the maternal-fetal interface in pregnancy

“…2a, 3d, 3e). It should be noted that the overexpression of IFI27 transcripts in both the peripheral blood cells and plasma was reported to be a potential biomarker for SARS-CoV-2 infection ( 39–41 ). Our results suggest that IFI27 upregulation could be a global immune cell response upon SARS-CoV-2 infection.…”

Polyadenylation ligation‐mediated sequencing (PALM‐Seq) characterizes cell‐free coding and non‐coding RNAs in human biofluids

“…Another interesting finding was that the SARS-CoV-2-biased codons in tRNA pools accumulated in the plasma of COVID-19 patients, which may increase the replication of the virus. 61 Using PALM-Seq, researchers could monitor the health status on many common RNA biotypes.…”

“…PALM‐Seq could capture exogenous genes from pneumonia‐related microorganisms in the plasma of COVID‐19 patients, offering a method to screen the immune response and microbial infection at the same time. Another interesting finding was that the SARS‐CoV‐2‐biased codons in tRNA pools accumulated in the plasma of COVID‐19 patients, which may increase the replication of the virus 61 . Using PALM‐Seq, researchers could monitor the health status on many common RNA biotypes.…”