Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

We investigated the immune events following SARS-COV-2 infection, from the acute inflammatory state up to four weeks post infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. The acute phase was characterized by a rapid migration of CD16+ monocytes from the blood and concomitant increase in CD16+ macrophages in the lungs. We identified two subsets of interstitial macrophages (DR+ CD206-), a transitional CD11c+ CD16+ population that was directly associated with IL-6 levels in plasma, and one long lasting CD11b+ CD16+ population. Strikingly, monocytes were a correlate of viral replication in bronchial brushes and levels of TARC (CCL17), and worse disease outcomes were associated with high levels of cell infiltration in lungs and CD11b+ CD16+ macrophages accumulation. Importantly, this accumulation was long-lasting and detectable even in animals with mild or no signs of disease. Interestingly, animals with less signs of disease had a high IL-10:IL-6 ratio. Our results unravel cellular mechanisms of COVID-19 and validate NHP as models to test immune therapies.