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New study by @IdoAmitLab on scRNA-seq in mild (n=3) vs severe (n=6) COVID-19 patient, w/ computational disentangling of cells directly infected by SARS-CoV-2 vs those indirectly impacted.
https://www.sciencedirect.com/science/article/pii/S0092867420305687
https://www.sciencedirect.com/science/article/pii/S0092867420305687
SARS-CoV-2 mainly infects the epithelial and macrophage subsets in BAL, with indirect effects on naive CD4+ T cells, NK cells, neutrophils, monocytes/monocyte-derived macrophages.
In severe COVID-19 patients there is a *decrease* in alveolar macrophages (ingest inhaled particles, leading to degradation, clearance and presentation of Ag to adaptive immune cells) and an *increase* in monocyte-derived macrophages and monocytes.
These observations underscore the "double-edge sword" of the immune response in COVID-19: early in SARS-CoV-2 infection myeloid cells are important in clearing virus and later myeloid cells *may* cause excessive inflammation and exacerbate tissue damage.
Therapies that boost alveolar macrophages (e.g., interferon-beta-1b) may be effective in clearing virus, especially if administered early, as suggest by the recent @TheLancet study. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31042-4/fulltext
While later in disease therapies that inhibit migration of pro-inflammatory monocyte-derived macrophages (eg, CCR2/5 inhibitors) or suppress inflammation (eg., anti-IL6/6R, anti-TNF, anti-IL8, IVIG, JAKi) *may* be beneficial in treating the maladaptive immune response.
