Jeong Seok Lee1,8,*, June-Young Koh2,8, Kijong Yi2,8, Young-Il Kim3,8, Su-Jin Park3,4, Eun-Ha Kim3, Se-Mi Kim3, Sung Ho Park5, Young Seok Ju1,2,6, Young Ki Choi3,7,* & Su-Hyung Park2,6,*
1GENOME INSIGHT Inc., Daejeon, Republic of Korea.
2Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
3College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
4Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju, Korea.
5School of Life Sciences, Ulsan National Institute of Science & Technology (UNIST), Ulsan, Republic of Korea.
6The Center for Epidemic Preparedness, KAIST Institute, KAIST, Daejeon, Republic of Korea.
7Center for Study of Emerging and Re-emerging Viruses, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
8These authors contributed equally: Jeong Seok Lee, June-Young Koh, Kijong Yi, Young-Il Kim.
Few studies have used a longitudinal approach to describe the immune response to SARS-CoV-2 infection. Here, we perform single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment shows distinct changes in cell proportions and characteristics compared to uninfected control, at 2 and 5 days post-infection (dpi). Macrophages are classified into 10 distinct subpopulations with transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, notably at 2 dpi. Moreover, trajectory analysis reveals gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identifies a macrophage subpopulation that has rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we find that M1 or M2 macrophages show distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection.