RT Journal Article
SR Electronic
T1 Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.03.429351
DO 10.1101/2021.02.03.429351
A1 Kami Pekayvaz
A1 Alexander Leunig
A1 Rainer Kaiser
A1 Sophia Brambs
A1 Markus Joppich
A1 Aleksandar Janjic
A1 Oliver Popp
A1 Vivien Polewka
A1 Lucas E. Wange
A1 Christoph Gold
A1 Marieluise Kirchner
A1 Maximilian Muenchhoff
A1 Johannes C Hellmuth
A1 Clemens Scherer
A1 Tabea Eser
A1 Flora Deák
A1 Niklas Kuhl
A1 Andreas Linder
A1 Kathrin Saar
A1 Lukas Tomas
A1 Christian Schulz
A1 Wolfgang Enard
A1 Inge Kroidl
A1 Christof Geldmacher
A1 Michael von Bergwelt-Baildon
A1 Oliver T. Keppler
A1 Ralf Zimmer
A1 Philipp Mertins
A1 Norbert Hubner
A1 Michael Hölscher
A1 Steffen Massberg
A1 Konstantin Stark
A1 Leo Nicolai
YR 2021
UL http://biorxiv.org/content/early/2021/02/03/2021.02.03.429351.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.