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Integration and Reanalysis of Four RNA-Seq Datasets Including BALF, Nasopharyngeal Swabs, Lung Biopsy, and Mouse Models Reveals Common Immune Features of COVID-19

  • Rudi Alberts (Department of Microbiology and Immunology, NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Sze Chun Chan (Department of Microbiology and Immunology, NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Qian-Fang Meng (Shengzhen Bay Laboratory) ;
  • Shan He (School of Biological Sciences, Nanyang Technological University) ;
  • Lang Rao (Shengzhen Bay Laboratory) ;
  • Xindong Liu (Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University(Army Medical University)) ;
  • Yongliang Zhang (Department of Microbiology and Immunology, NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore)
  • Received : 2022.02.07
  • Accepted : 2022.04.27
  • Published : 2022.06.30
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Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

Keywords

Acknowledgement

This work was supported by grants from the Singapore National Medical Research Council (NMRC/OFIRG/0059/2017 to Y. Z.) and the National University Health System (NUHSRO/2020/113/T1/Seed-Mar/09 to Y. Z.).

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