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Impaired function of white blood cells in severe COVID-19 courses

Members of the Cluster of Excellence ImmunoSensation2 and a team of international scientists find persistent dysfunction of Natural Killer cells in severe COVID-19 courses

The acute respiratory syndrome COVID-19, caused by coronavirus 2 (SARS-CoV-2), emerged in late 2019. Since then, a comprehensive understanding of both the virus itself and the respective host immune-response has rapidly been gained. Recent studies suggest a specific form of white immune cells, natural killer (NK) cells, to play a crucial role in the early antiviral immune response. But to what extend do NK cells contribute to the pathogenesis of severe COVID-19 infections? In a multicenter study, Scientists from the Cluster of Excellence Immunosensation2, located at the University Hospital Bonn and the German Center for Neurodegenerative Diseases (DZNE), together with an international team, have now been able to investigate the role of NK cells in the progression of COVID-19 in detail.

As part of the antiviral immune response, NK cells are able to both detect and eliminate virus-infected host cells. To classify the functionality and the molecular properties of NK cells throughout the course of a COVID-19 infection, blood samples of 205 patients were collected. The samples were taken in between the 1st and 6th week after symptom onset.

Persistent dysfunction of NK cells in severe COVID-19 courses

Already in the very early stage of severe disease, NK cells display a specific molecular fingerprint, that is attributable to the so-called type I interferons. This is accompanied by a significant dysfunction that persists for several weeks.

This impaired functionality was also observed for NK cells originating from COVID-19 patients with moderate symptoms. But here, functionality normalized after a short time.

NK cells lose antifibrotic activity

Severe COVID-19 infections are regularly accompanied by pulmonary fibrosis. Functional NK cells are known to exhibit antifibrotic activity. Analysing NK cells originating from severe courses three weeks after infection showed molecular patterns resembling those observed in other immune cells in the context of fibrosis formation. In line with this observation, NK cells had significantly lost their antifibrotic capacity, which may have an impact in fibrotic remodeling of the lung.

In summary, these data provide a detailed insight into the role of NK cells in the immunopathogenesis of COVID-19. Future studies will have to show whether this may aid the development of novel therapeutic approaches.

National and international cooperation

As contribution to the overall endeavor to better understand SARS-CoV 2 and the COVID-19 infection, the scope and pace of the work presented was possible only by collaboration of many partners from Berlin, Kiel, Düsseldorf, New Castle (UK) and Seattle (USA).


Participating institutions and funding

In addition to the researchers mentioned, other national and international groups from the following centers participated: Bonn University Hospital (PD Dr. Beate Kümmerer, Dr. Florian Schmidt, Professor Dr. Eicke Latz), Charité Berlin (Professor Dr. Leif Erik Sander, Professor Dr. Birgit Sawitzki), Kiel University Hospital (Professor Dr. Philipp Rosenstiel), Düsseldorf University Hospital (Professor Dr. Verena Keitel), Newcastle University (Professor Dr. Muzlifah Haniffa), and the University of Washington (Professor Dr. James R. Heath).

The study was funded by the German Research Foundation (DFG), the German Federal Ministry of Education and Research (BMBF), the German Center for Infection Research (DZIF) and the DZNE.


Publication

Benjamin Krämer*, Rainer Knoll*, Lorenzo Bonaguro*, Michael ToVinh*, Jan Raabe et.al.: Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19. Immunity. https://www.sciencedirect.com/science/article/pii/S1074761321003654?via%3Dihub

Contact:

Prof. Dr. Jacob Nattermann

Hepatogastroenterologie

Medizinische Klinik und Poliklinik I

Uniklinikum Bonn

Tel.: +49 (0)228 287 -12230

jacob.nattermann@ukbonn.de


Prof. Dr. Joachim Schultze

Direktor Systemmedizin

Deutsches Zentrum für Neurodegenerative

Erkrankungen (DZNE)

Tel.: +49 (0) 228 43302-410

joachim.schultze@dzne.de

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