2023/04/25
Osaka University
RIKEN
Keio University
Japan Science and Technology Agency
Highlights of the Research Achievements
Conducted a single-cell analysis of approximately 900,000 peripheral blood mononuclear cells (PBMCs) from 148 Japanese individuals (73 COVID-19 patients and 75 healthy donors), along with an integrated analysis of host genomic information.
Discovered that CD14+CD16++ monocytes, a rare subtype of monocytes, are involved in the severity of COVID-19.
Found that genes associated with severe COVID-19 identified through genome-wide association studies (GWAS), such as *IFNAR2*, primarily function specifically in monocytes and dendritic cells.
The findings are expected to lead to the development of new therapeutic and diagnostic methods for various infectious diseases, including COVID-19.
A research group from Osaka University's Graduate School of Medical Sciences—including Tatsuya Ebihiro (Doctoral Programs) (Department of Statistical Genetics/Department of Respiratory Medicine and Clinical Immunology), Yuya Shirai (Doctoral Programs) (Department of Statistical Genetics/Department of Respiratory Medicine and Clinical Immunology), Professor Atsushi Kumanogoh (Department of Respiratory Medicine and Clinical Immunology), and Professor Yukinori Okada (Department of Statistical Genetics/Graduate School of Medical Sciences, The University of Tokyo, Department of Statistical Genetics/Team Leader, Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences)—has revealed the role of innate immune cells in severe COVID-19 by conducting an integrated analysis of single-cell information from PBMCs and host genomic information.
Although abnormal responses of blood immune cells have been reported to be involved in severe COVID-19, much remains unknown about the host's immune response to SARS-CoV-2 infection. Furthermore, while large-scale GWAS have revealed the contribution of host genetic risk to severe COVID-19, the underlying pathogenic mechanisms had not been fully elucidated.
In this study, the research group conducted a single-cell analysis of PBMCs from a Japanese cohort collected by Osaka University, comprising 73 COVID-19 patients and 75 healthy donors, and performed an integrated analysis with host genomic information. The results showed that CD14+CD16++monocytes, a rare subtype of monocytes, were significantly reduced in COVID-19 patients, and that this was partly due to impaired cell differentiation into CD14+CD16++monocytes. Furthermore, through analysis of gene expression changes and cell-cell interactions, they also found that the dysfunction of CD14+CD16++monocytes is involved in disease severity. Moreover, they discovered that genes associated with severe COVID-19 identified by GWAS are specifically expressed in monocytes and dendritic cells, and that genetic polymorphisms related to COVID-19 have cell-type-specific eQTL (expression quantitative trait loci) effects under SARS-CoV-2 infection conditions.
This research identified the cell types involved in severe COVID-19 and found that the host's genetic risk for severe disease is concentrated in innate immune cells. These findings are expected to contribute to future research on infectious diseases.
For the full press release, please see below.