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Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

Item Type:Preprint
Title:Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection
Creators Name:Pekayvaz, K. and Leunig, A. and Kaiser, R. and Brambs, S. and Joppich, M. and Janjic, A. and Popp, O. and Polewka, V. and Wange, L.E. and Gold, C. and Kirchner, M. and Muenchhoff, M. and Hellmuth, J.C. and Scherer, C. and Eser, T. and Deák, F. and Kuhl, N. and Linder, A. and Saar, K. and Tomas, L. and Schulz, C. and Enard, W. and Kroidl, I. and Geldmacher, C. and von Bergwelt-Baildon, M. and Keppler, O.T. and Zimmer, R. and Mertins, P. and Hubner, N. and Hölscher, M. and Massberg, S. and Stark, K. and Nicolai, L.
Abstract:The immune system of most SARS-CoV-2 infected individuals limits viral spread to the upper airways without pulmonary involvement. This prevents the development of pneumonic COVID-19. However, the protective immunological responses causative of successful viral containment in the upper airways remain unclear. Here, we combine longitudinal single-cell RNA sequencing, proteomic profiling, multidimensional flow cytometry, RNA-Seq of FACS-sorted leukocyte subsets and multiplex plasma interferon profiling to uncover temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients. We compare host responses in a high-risk patient population infected with SARS-CoV-2 but without pulmonary involvement to patients with COVID-19 pneumonia. Our data reveal a distinct immunological signature of successful viral containment, characterized by an early prominent interferon stimulated gene (ISG) upregulation across immune cell subsets. In addition, reduced cytotoxic potential of Natural Killer (NK) and T cells, as well as a monocyte phenotype with immune-modulatory potential are hallmarks of protective immunity. Temporal resolution across disease trajectories highlights ISG upregulation as particularly prominent early in the disease and confirms increased expression also in comparison to healthy controls. We validate this distinct temporal ISG signature by in-depth RNA-seq of FACS-sorted leukocyte subsets in a large prospective ambulatory SARS-CoV-2 infected cohort confirming early and robust ISG upregulation particularly in monocytes and T cells. In conclusion, our data demonstrate a protective ISG phenotype in patients with successful containment of SARS-CoV-2 infection without progression to COVID-19. This early protective interferon response might be exploited as a therapeutic approach and for disease course prediction.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2021.02.03.429351
Date:3 February 2021
Official Publication:https://doi.org/10.1101/2021.02.03.429351
Related to:
https://edoc.mdc-berlin.de/21373/Final version

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