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

• Published in: Nature communications Vol. 11; no. 1; p. 6078
• Main Authors: Fahlberg, M D, Blair, R V, Doyle-Meyers, L A, Midkiff, C C, Zenere, G, Russell-Lodrigue, K E, Monjure, C J, Haupt, E H, Penney, T P, Lehmicke, G, Threeton, B M, Golden, N, Datta, P K, Roy, C J, Bohm, R P, Maness, N J, Fischer, T, Rappaport, J, Vaccari, M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 27.11.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Acute Disease; Animal diseases; Animal models; Animals; Brushes; CCL17 protein; CD11b antigen; CD11c antigen; CD16 antigen; Coronaviruses; COVID-19; COVID-19 - diagnosis; COVID-19 - immunology; COVID-19 - pathology; COVID-19 - virology; Cytokines - metabolism; Disease Models, Animal; Disease Progression; Female; Histocompatibility antigen HLA; Humans; Immune response; Immune response (cell-mediated); Immune system; Inflammation; Interleukin 10; Interleukin 6; Leukocyte migration; Leukocytes (neutrophilic); Lung - cytology; Lung - immunology; Lung - virology; Lung diseases; Lungs; Macaca mulatta - immunology; Macaca mulatta - virology; Macrophages; Macrophages - immunology; Male; Monocytes; Monocytes - immunology; Monocytes - metabolism; Neutrophils - immunology; Neutrophils - metabolism; Pathology; Primates; SARS-CoV-2 - immunology; SARS-CoV-2 - isolation & purification; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Tryptophan; Vaccines; Viral diseases; Viral Load - immunology; Virus Replication - immunology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19967-4

Understanding SARS-CoV-2 associated immune pathology is crucial to develop pan-effective vaccines and treatments. Here we investigate the immune events from the acute state up to four weeks post SARS-CoV-2 infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. We show a robust migration of CD16 expressing monocytes to the lungs occurring during the acute phase, and we describe two subsets of interstitial macrophages (HLA-DR CD206 ): a transitional CD11c CD16 cell population directly associated with IL-6 levels in plasma, and a long-lasting CD11b CD16 cell population. Trafficking of monocytes is mediated by TARC (CCL17) and associates with viral load measured in bronchial brushes. We also describe associations between disease outcomes and high levels of cell infiltration in lungs including CD11b CD16 macrophages and CD11b neutrophils. Accumulation of macrophages is long-lasting and detectable even in animals with mild or no signs of disease. Interestingly, animals with anti-inflammatory responses including high IL-10:IL-6 and kynurenine to tryptophan ratios show less severe illness. Our results unravel cellular mechanisms of COVID-19 and suggest that NHP may be appropriate models to test immune therapies.