Recently, emerging evidence has indicated that COVID-19 represents a major threat to older populations, but the underlying mechanisms remain unclear. The pathogen causing COVID-19 is acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection depends on the key entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Recognizing the importance of ACE2 and TMPRSS2 for the cellular tropism of SARS-CoV-2, we analyzed and presented the landscape of cell-type identities for ACE2 + TMPRSS2 + cells across different human tissues and the age-related alterations in ACE2 and TMPRSS2 expression across different cell types. Additionally, most of the post-acute COVID-19 sequelae could attribute to the ACE2-expressing organ systems. Therefore, these SARS-CoV-2 tropism data should be an essential resource for guiding clinical treatment and pathological studies, which should draw attention toward the prioritization of COVID-19 research in the future. Notably, we discovered the age-related expression of ACE2 and TMPRSS2 in the immune-inflammatory stromal cells, implying the potential interplay between COVID-19, stromal cells, and aging. In this study, we developed a novel and practical analysis framework for mapping the cellular tropism of SARS-CoV-2. This approach was built to aid the identification of viral-specific cell types and age-related alterations of viral tropism, highlighting the power of single-cell RNA sequencing (scRNA-seq) to address viral pathogenesis systematically. With the rapid accumulation of scRNA-seq data and the continuously increasing insight into viral entry factors, we anticipate that this scRNA-seq-based approach will attract broader interest in the virus research communities.
【저자키워드】 SARS-CoV-2, ACE2, human tissues, immune-inflammatory stromal cells, TMPRSS2, 【초록키워드】 COVID-19, coronavirus, SARS-COV-2 infection, viral pathogenesis, virus, angiotensin-converting enzyme 2, viral entry, Single-cell RNA sequencing, pathogen, cells, Research, Factors, resource, expression, scRNA-seq, mechanism, Evidence, Analysis, Clinical treatment, cell types, cell type, organ systems, identity, viral tropism, acute respiratory syndrome, Older, alteration, transmembrane serine protease, TMPRSS2 expression, scRNA-seq data, COVID-19 research, cellular tropism, approach, populations, Cell, analyzed, indicated, human tissue, highlighting, 【제목키워드】 Human, tropism, stromal cell,