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Pekayvaz, Kami ORCID: 0000-0003-4040-650X; Leunig, Alexander; Kaiser, Rainer; Joppich, Markus; Brambs, Sophia; Janjic, Aleksandar; Popp, Oliver; Nixdorf, Daniel; Fumagalli, Valeria; Schmidt, Nora; Polewka, Vivien; Anjum, Afra; Knottenberg, Viktoria; Eivers, Luke; Wange, Lucas E.; Gold, Christoph; Kirchner, Marieluise; Muenchhoff, Maximilian; Hellmuth, Johannes C.; Scherer, Clemens; Rubio-Acero, Raquel; Eser, Tabea; Deák, Flora; Puchinger, Kerstin; Kuhl, Niklas; Linder, Andreas; Saar, Kathrin; Tomas, Lukas; Schulz, Christian; Wieser, Andreas; Enard, Wolfgang; Kroidl, Inge; Geldmacher, Christof; Bergwelt-Baildon, Michael von; Keppler, Oliver T.; Munschauer, Mathias; Iannacone, Matteo; Zimmer, Ralf; Mertins, Philipp; Hubner, Norbert; Hoelscher, Michael; Massberg, Steffen; Stark, Konstantin; Nicolai, Leo ORCID: 0000-0003-0776-5885 (2022): Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection. Nature Communications, 13: 1018. ISSN 2041-1723

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The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remains unclear. Here, we combine a multi-omics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype associated with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies.

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