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Out now! Our preprint on longitudinal lung and blood single-cell RNA-seq, and proteomics, of SARS-CoV-2 infected Syrian hamsters!
Fantastic collaboration of labs from @ChariteBerlin @FU_Berlin @MDC_Berlin @BIMSB_MDC https://www.biorxiv.org/content/10.1101/2020.12.18.423524v1
Summary in the thread below … (1/9)
Fantastic collaboration of labs from @ChariteBerlin @FU_Berlin @MDC_Berlin @BIMSB_MDC https://www.biorxiv.org/content/10.1101/2020.12.18.423524v1
Summary in the thread below … (1/9)
Syrian hamsters are a moderate disease model. They have quite some edemas in the lung, but recover after 10 days (see weight curve below and clearance of virus by RT-qPCR and staining). We have data from naive/2/3/5/14dpi. … (2/9)
In the lung we determine all cell types, particularly also tissue cells (hardly captured in bronchoalveolar lavages from patients). We see influx of macrophages in the lung (top right) and lymphopenia in blood (bottom right). … (3/9)
Proteomics was used to match with patient data, e.g. increase of Lgals3/Lgals3bp in the hamster lungs. … (4/9)
Strongest and earliest transcriptional response in the response is by monocytes/macrophages. Alveolar type 2 (AT2) cells, likely primary target for replication, respond only weakly. … (5/9)
We saw only about 10% of AT2 cells being infected, and also low ACE2 levels. This was also shown in a recent preprint on ex vivo infected human lung tissue (check out https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3687020 !) … (6/9)
Monocytic macrophages (MoMa) take up lots of virus (top right), and at 2dpi/3dpi show dose-dependent of e.g. pro-inflammatory cytokines (likely TLR/NF-kappaB signaling, left). … (7/9)
Endothelial cell subsets (capillary, bronchial, artery, vein) show distinct responses and produce a range of cytokines (see Fig. 6 in the manuscript). … (8/12)
At 5dpi we see strong T cell activity, both in endothel stainings (left) and in the scRNA-seq (Interferon gamma activation, top middle) and "doublets"… (bottom right no indication of cytotoxic activity, more likely adherence/transmigration). And IgM (top right)! (9/12)
Summary: we have a very detailed profiling of a moderate COVID-19 disease model. Transcriptional/pro-inflammatory response mostly by monocytes/macrophages, dose-dependent on viral RNA uptake. Distinct response by endothel subtypes. … (10/12)
Strong T cell recruitement and efficient clearing of the infection. (11/12)
Strong T cell recruitement and efficient clearing of the infection. All data immediately available! Check https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162208 for raw/processed data and https://github.com/Berlin-Hamster-Single-Cell-Consortium (very much under construction) for code. (12/12)
Feel free to ask/DM me your questions/comments!
Feel free to ask/DM me your questions/comments!
