In:
Genome Research, Cold Spring Harbor Laboratory, Vol. 32, No. 2 ( 2022-02), p. 228-241
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.
Type of Medium:
Online Resource
ISSN:
1088-9051
,
1549-5469
DOI:
10.1101/gr.276175.121
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2022
detail.hit.zdb_id:
1483456-X
SSG:
12
Permalink
