Journal Article

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

Michael von Bergwelt-Baildon, Matteo Iannacone, Nora Schmidt, Niklas Kuhl, Oliver T. Keppler, Andreas Wieser, Konstantin Stark, Ralf Zimmer, Tabea Eser, Michael Hoelscher, Kami Pekayvaz, Daniel Nixdorf, Philipp Mertins, Rainer Kaiser, Luke Eivers, Norbert Hubner, Lucas E. Wange, Steffen Massberg, Christoph Gold, Andreas Linder, Johannes C. Hellmuth, Viktoria Knottenberg, Markus Joppich, Alexander Leunig, Inge Kroidl, Sophia Brambs, Lukas Tomas, Afra Anjum, Kathrin Saar, Leo Nicolai, Valeria Fumagalli, Raquel Rubio-Acero, Christof Geldmacher, Christian Schulz, Flora Deák, Maximilian Muenchhoff, Clemens Scherer, Vivien Polewka, Wolfgang Enard, Oliver Popp, Aleksandar Janjic, Marieluise Kirchner, Kerstin Puchinger, Mathias Munschauer

2022

Overview

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. Infection with SARS-COV-2 can result in self-limited upper airway infection or progress to a more systemic inflammatory condition including pneumonic COVID-19. Here the authors utilise a multi-omics approach to interrogate the immune response of patients with self-limiting upper respiratory SARS-CoV-2 infection and reveal a temporal immune trajectory they associate with viral containment and restriction from pneumonic progressive disease.

• Publisher: Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/21 / 13/31 / 49/91 / 631/250/24/2510 / 631/250/254 / 631/250/255/2514 / 631/326/596/4130 / 82/1 / 82/58 / Adult / Aged / Aged, 80 and over / Ambulatory Care / Antiviral drugs / Cardiovascular and Metabolic Diseases / Containment / Coronaviruses / COVID-19 / COVID-19 - immunology / Cytokines / Cytokines - blood / Cytotoxicity / Female / Gene Expression Regulation / Gene Regulatory Networks / Genes, Cells and Cell-Based Medicine [Topic 1] / Humanities and Social Sciences / Humans / Immune response / Immune system / Immunology / Immunomodulation / Infections / Inflammation / Interferon / Interferons / Interferons - immunology / Killer Cells, Natural / Killer Cells, Natural - immunology / Longitudinal Studies / Lymphocytes / Lymphocytes T / Male / Middle Aged / Molecular Processes and Therapies [Topic 2] / Monocytes / Monocytes - immunology / multidisciplinary / Nasopharynx / Nasopharynx - immunology / Nasopharynx - virology / Natural killer cells / Phenotypes / Q / Respiratory tract / SARS-CoV-2 / SARS-CoV-2 - physiology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / T-Lymphocytes / T-Lymphocytes - immunology / Technology Platforms / Viral diseases