Single-cell RNA analysis reveals the potential risk of organ-specific cell types vulnerable to SARS-CoV-2 infections

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of coronavirus disease 2019 (COVID-19) since December 2019 that has led to more than 160 million confirmed cases, including 3.3 million deaths. To understand the mechanism by which SARS-CoV-2 invades human cells and reveal organspecific susceptible cell types for COVID-19, we conducted comprehensive bioinformatic analysis using public single-cell RNA sequencing datasets. Utilizing the expression information of six confirmed COVID-19 receptors (ACE2, TMPRSS2, NRP1, AXL, FURIN and CTSL), we demonstrated that macrophages are the most likely cells that may be associated with SARS-CoV-2 pathogenesis in lung. Besides the widely reported 'chemokine storm', we identified ribosome related pathways that may also be potential therapeutic target for COVID-19 lung infection patients. Moreover, cell-cell communication analysis and trajectory analysis revealed that M1-like macrophages showed the highest relation to severe COVID-19 patients. And we also demonstrated that upregulation of chemokine pathways generally lead to severe symptoms, while down-regulation of ribosome and RNA activity related pathways are more likely to be mild. Other organ-specific susceptible cell type analyses could also provide potential targets for COVID-19 therapy. This work can provide clues for understanding the pathogenesis of COVID-19 and contribute to understanding the mechanism by which SARS-CoV-2 invades human cells.

Automated summary

This study used single-cell RNA sequencing analysis to identify macrophages as potentially associated with SARS-CoV-2 lung pathogenesis and ribosome-related pathways as potential therapeutic targets for COVID-19 lung infection. M1-like macrophages showed a strong relationship with severe COVID-19 patients, with upregulation of chemokine pathways leading to severe symptoms and down-regulation of ribosome and RNA activity pathways potentially leading to milder cases. Additionally, analysis of organ-specific susceptible cell types could provide further targets for COVID-19 therapy.