Research

Plasma cell-free RNA characteristics in COVID-19 patients

    • 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, Guangdong, China;
    • 2BGI-Shenzhen, Shenzhen 518083, Guangdong, China;
    • 3College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;
    • 4Technology Center, Guangzhou Customs, Guangzhou 510623, China;
    • 5School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China;
    • 6The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, Guangdong, China;
    • 7Yangjiang People's Hospital, Yangjiang 529599, Guangdong, China;
    • 8Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China;
    • 9College of Informatics, Huazhong Agricultural University, Wuhan 430070, China;
    • 10Shenzhen Bay Laboratory, Shenzhen 518132, China;
    • 11Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, 518120, China;
    • 12China National Genebank, BGI-Shenzhen, Shenzhen 518120, China;
    • 13Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, BGI-Shenzhen, Shenzhen, 518120, China;
    • 14Institute of Infectious Disease, Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510060, China
    • 15 These authors contributed equally to this work.
Published January 21, 2022. https://doi.org/10.1101/gr.276175.121
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cover of Genome Research Vol 36 Issue 6
Current Issue:
June 2026, Vol. 36, No. 6
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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.

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