PT  - JOURNAL ARTICLE
AU  - Neal G. Ravindra
AU  - Mia Madel Alfajaro
AU  - Victor Gasque
AU  - Victoria Habet
AU  - Jin Wei
AU  - Renata B. Filler
AU  - Nicholas C. Huston
AU  - Han Wan
AU  - Klara Szigeti-Buck
AU  - Bao Wang
AU  - Guilin Wang
AU  - Ruth R. Montgomery
AU  - Stephanie C. Eisenbarth
AU  - Adam Williams
AU  - Anna Marie Pyle
AU  - Akiko Iwasaki
AU  - Tamas L. Horvath
AU  - Ellen F. Foxman
AU  - Richard W. Pierce
AU  - David van Dijk
AU  - Craig B. Wilen
TI  - Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium
AID  - 10.1101/2020.05.06.081695
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.06.081695
4099  - http://biorxiv.org/content/early/2020/07/13/2020.05.06.081695.short
4100  - http://biorxiv.org/content/early/2020/07/13/2020.05.06.081695.full
AB  - SARS-CoV-2, the causative agent of COVID-19, has tragically burdened individuals and institutions around the world. There are currently no approved drugs or vaccines for the treatment or prevention of COVID-19. Enhanced understanding of SARS-CoV-2 infection and pathogenesis is critical for the development of therapeutics. To reveal insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2 we performed single-cell RNA sequencing of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface cultures over a time-course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target of infection, which we confirmed by electron microscopy. Over the course of infection, cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III IFNs and IL6 but not IL1. This results in expression of interferon-stimulated genes in both infected and bystander cells. We observe similar gene expression changes from a COVID-19 patient ex vivo. In addition, we developed a new computational method termed CONditional DENSity Embedding (CONDENSE) to characterize and compare temporal gene dynamics in response to infection, which revealed genes relating to endothelin, angiogenesis, interferon, and inflammation-causing signaling pathways. In this study, we conducted an in-depth analysis of SARS-CoV-2 infection in HBECs and a COVID-19 patient and revealed genes, cell types, and cell state changes associated with infection.Competing Interest StatementThe authors have declared no competing interest.