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

Pekayvaz, K.; Leunig, A.; Kaiser, R.; Joppich, M.; Brambs, S.; Janjic, A.; Popp, O.; Nixdorf, D.; Fumagalli, V.; Schmidt, N.; Polewka, V.; Anjum, A.; Knottenberg, V.; Eivers, L.; Wange, L. E.; Gold, C.; Kirchner, M.; Muenchhoff, M.; Hellmuth, J. C.; Scherer, C.; Rubio-Acero, R.; Eser, T.; Deak, F.; Puchinger, K.; Kuhl, N.; Linder, A.; Saar, K.; Tomas, L.; Schulz, C.; Wieser, A.; Enard, W.; Kroidl, I.; Geldmacher, C.; von Bergwelt-Baildon, M.; Keppler, O. T.; Munschauer, M.; Iannacone, M.; Zimmer, R.; Mertins, P.; Hubner, N.; Hoelscher, M.; Massberg, S.; Stark, K.; Nicolai, L.

doi:10.1038/s41467-022-28508-0

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.

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection / Pekayvaz, K.; Leunig, A.; Kaiser, R.; Joppich, M.; Brambs, S.; Janjic, A.; Popp, O.; Nixdorf, D.; Fumagalli, V.; Schmidt, N.; Polewka, V.; Anjum, A.; Knottenberg, V.; Eivers, L.; Wange, L. E.; Gold, C.; Kirchner, M.; Muenchhoff, M.; Hellmuth, J. C.; Scherer, C.; Rubio-Acero, R.; Eser, T.; Deak, F.; Puchinger, K.; Kuhl, N.; Linder, A.; Saar, K.; Tomas, L.; Schulz, C.; Wieser, A.; Enard, W.; Kroidl, I.; Geldmacher, C.; von Bergwelt-Baildon, M.; Keppler, O. T.; Munschauer, M.; Iannacone, M.; Zimmer, R.; Mertins, P.; Hubner, N.; Hoelscher, M.; Massberg, S.; Stark, K.; Nicolai, L.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 13:1(2022). [10.1038/s41467-022-28508-0]