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Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates
Marissa D Fahlberg; Robert V Blair; Lara A Doyle-Meyers; Cecily C Midkiff; Giorgio Zenere; Kasi E Russell-Lodrigue; Christopher J Monjure; Toni P Penney; Gabrielle Lehmicke; Brienna M Threeton; Nadia Golden; Presan K Datta; Chad J Roy; Rudolph P Bohm; Nicholas J Maness; Tracy Fischer; Jay Rappaport; Monica Vaccari.
Affiliation
  • Marissa D Fahlberg; Tulane National Primate Research Center, Covington, LA
  • Robert V Blair; Tulane National Primate Research Center, Covington, LA
  • Lara A Doyle-Meyers; Tulane National Primate Research Center, Covington, LA
  • Cecily C Midkiff; Tulane National Primate Research Center, Covington, LA
  • Giorgio Zenere; Tulane National Primate Research Center, Covington, LA
  • Kasi E Russell-Lodrigue; Tulane National Primate Research Center, Covington, LA
  • Christopher J Monjure; Tulane National Primate Research Center, Covington, LA
  • Toni P Penney; Tulane National Primate Research Center, Covington, LA
  • Gabrielle Lehmicke; Tulane National Primate Research Center, Covington, LA
  • Brienna M Threeton; Tulane National Primate Research Center, Covington, LA
  • Nadia Golden; Tulane National Primate Research Center, Covington, LA
  • Presan K Datta; Tulane National Primate Research Center, Covington, LA
  • Chad J Roy; Tulane National Primate Research Center, Covington, LA
  • Rudolph P Bohm; Tulane National Primate Research Center, Covington, LA
  • Nicholas J Maness; Tulane National Primate Research Center, Covington, LA
  • Tracy Fischer; Tulane National Primate Research Center, Covington, LA
  • Jay Rappaport; Tulane National Primate Research Center, Covington, LA
  • Monica Vaccari; Tulane National Primate Research Center, Covington, LA
Preprint in English | bioRxiv | ID: ppbiorxiv-213777
ABSTRACT
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 robust and rapid migration of monocytes expressing CD16 from the blood and concomitant increase in CD16+ macrophages in the lungs. We identified two subsets of interstitial macrophages (HLA-DR+ CD206-), a transitional CD11c+ CD16+ cell population that was directly associated with IL-6 levels in plasma, and one long lasting CD11b+ CD16+ cell population. Strikingly, levels of monocytes were a correlate of viral replication in bronchial brushes and we discovered TARC (CCL17) as a new potential mediator of myeloid recruitment to the lungs. Worse disease outcomes were associated with high levels of cell infiltration in lungs including CD11b+ CD16hi macrophages and CD11b+ neutrophils. Accumulation of macrophages was long-lasting and detectable even in animals with mild or no signs of disease. Interestingly, animals with anti-inflammatory responses including high IL-10IL-6 and kynurenine to tryptophan ratios had less signs of disease. Our results unravel cellular mechanisms of COVID-19 and suggest that NHP may be appropriate models to test immune therapies.
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint
Fulltext
Add to My VHL
Print
XML
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint