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We are excited to share ‘Host-viral infection maps reveal signatures of severe COVID-19 patients’ https://www.cell.com/cell/fulltext/S0092-8674(20)30568-7 led by @bost_pierre and @AmirGiladi. Collab with the Zheng Lab from the Shenzhen Third People’s Hospital and Benno Schwikowski from @institutpasteur 1/13
Emerging viral infections are a constant threat to global health, as shown by the current COVID-19 outbreak, and tools to molecularly dissect host-viral interactions are lacking. 2/13
We developed Viral-Track, a new computational tool, which allows unsupervised detection of viral RNA in scRNA-seq datasets, and transcriptional sorting of infected versus bystander cells. 3/13
Viral-Track was benchmarked and validated on multiple mouse in-vivo infection models - including Influenza, LCMV and VSV infections - as well as on human HBV infection. 4/13
In all cases, Viral-Track detected correctly the specific viral strain and enabled to define mechanisms of viral infections. 5/13
We sequenced the Broncho-Alveolar Lavage of 3 mild and 6 severe COVID-19 patients to study how the SARS-CoV-2 modifies the lung cellular landscape. 6/13
A major perturbation revealed in severe COVID-19 patients included depletion of the alveolar macrophages, which are suppressive immune cells protecting the lung tissue from excessive inflammation. 7/13
Immune lung cells in the severe patients are dominated by infiltrating myeloid cells, characterized by inflammatory signaling, including the cytokines IL6 and IL8. 8/13
These result suggests that potential treatments that maintain the alveolar macrophage integrity, such as GM-CSF, an important alveolar macrophage growth factor, may prove a viable treatment. 9/13
We found evidence of SARS-CoV-2 infection in epithelial populations, as well as in monocytes in severe patients 10/13
In one of the severe patients, Viral-Track unexpectedly detected traces of co-infection by the hMPV virus – a virus which was shown to target immune-compromised and SARS-CoV infected patients. 11/13
We show hMPV infects the monocyte compartment, perturbing their type-I IFN signaling pathway. 12/13
Applying Viral-Track to larger clinical cohorts could provide critical mechanistic understanding of SARS-CoV-2 interactions with its human host and devise new treatment strategies for severe patients. 13/13
better access here: https://www.sciencedirect.com/science/article/pii/S0092867420305687 (thanks to @UlrikStervbo )
