Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates
cell biology immunology/immunity inflammation
Authors: Fahlberg et al.
Link to paper: https://www.biorxiv.org/content/10.1101/2020.07.21.213777v1
Tags: Cell Biology, Immunology/Immunity, Inflammation
African green monkeys and rhesus macaques were infected with SARS-CoV-2 via musocal (multiple) or intranasal route replicating the human phenotype of infection.
High levels of monocyte infiltration in lungs andCD11b+ CD16+ macrophage accumulation were associated with worse outcome but also detectable in mild and asymptomatic animals.
The ratio of plasma levels IL-10 to IL-6, rather than IL-6 level alone, was associated with disease severity and pathological score
Two species of non-human primates (4 Rhesus macaques and 4 African green monkeys) were inoculated with the SARS-CoV-2 virus either via the aerosol route or the mucosal challenge and then they were followed for four weeks. Authors detected increased infiltration of monocytes, interstitial macrophages, NHG2a+ NK cells and PD-1+ T cells into the lungs. Two populations of macrophages were particularly upregulated in the bronchoalveolar lavage: CD11c+CD16+HLA-DR+ (transiently) and CD11b+CD16+HLA-DR+ (stably). Contrary to the previous reports, authors did not detect increased levels of neutrophils. Overall, this study reports cellular changes in the COVID-19-positive NHPs and further validates the NHP model for future studies.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19 – longitudinal (4 weeks) study of the immune response in 8 NHPs
In vivo study (NHP)
Strengths and limitations of the paper
Novelty: This preprint contributes to the current literature by providing longitudinal study (4 weeks) of the cellular changes in the NHP model.
Standing in the field: Mostly in agreement. The monocyte and macrophage infiltration has been previously reported. Contrary to the literature, authors did not observe increased neutrophil levels.
Appropriate statistics: Mostly appropriate. It would be nice to add the details of statistical tests within the figure descriptions. Potentially, other than the Dunn’s multiple comparison test might be used as this test is one of the least powerful ones.
Viral model used: SARS-CoV-2 (2019-nCoV/USA-WA1/2020 363 409 (MN985325.1))
Translatability: Validation of NHP as a model that might be used for drug discovery or vaccine testing (especially if the reported cellular changes are observed in human patients as well)
Main limitations: 1) Association between the viral replication in BAL and TARC levels or the absolute number of monocytes was significant only when the animals were grouped together, not when they were analysed separately.
2) Neutrophilia has been consistently reported in COVID-19-positive patients and was implicated in the immunopathology; however, this was not observed in these animals.
3) Aspects of the disease differed between the two different NHP models for example the detection of the viral load. Potentially, more profound comparison between these two different models would increase the translatability of these models.