Abstract
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+CD16hi 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.
Highlights
Understanding SARS-CoV-2 associated immune pathology is crucial to develop pan-effective vaccines and treatments
The increase in IL-6 coincides with the upregulation of chemokines responsible for myelopoiesis and monocyte recruitment to the lungs[3,10] suggesting that peripheral inflammatory monocytes and tissue macrophages may have a role in the cytokine storm seen in severe COVID-19 patients[11]
Four adult rhesus macaques (RM) and four adults African green monkeys (AGM) were exposed to SARS-CoV-2 by either aerosol or mucosal challenge including buccal, intranasal, intratracheal, and conjunctival exposure (Supplementary Table 1)
Summary
Understanding SARS-CoV-2 associated immune pathology is crucial to develop pan-effective vaccines and treatments. Studies elucidating molecular and immunological details of SARS‐CoV-2 infection are underway, and many of the reported clinical observations point to the disease being at least partly the result of an excessive host response aimed to clear the virus but instead contributing to disease development[3] This hypothesis is supported by studies on the closely related coronavirus SARS-CoV-14–6, and by clinical reports showing elevated levels of the pro-inflammatory cytokine. Non-human primates (NHP) have been used as animal models to study acute respiratory diseases such as SARS and MERS13 In these studies, African green monkeys (AGM) have been shown to be more susceptible to severe disease than rhesus macaques (RM)[14]. Other groups have described the very early immune events in SARS-CoV-2 infected rhesus macaques, with perturbation of monocytes populations, increased macrophages in lungs, and cellular activation in blood all happening a few days following the infection[16]
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