COVID-19: Immune system derails

Date:
August 6, 2020
Source:
DZNE - German Center for Neurodegenerative Diseases
Summary:
Contrary to what has been generally assumed so far, a severe course
of COVID-19 does not solely result in a strong immune reaction --
rather, the immune response is caught in a continuous loop of
activation and inhibition.



FULL STORY ========================================================================== Contrary to what has been generally assumed so far, a severe course of
COVID-19 does not solely result in a strong immune reaction -- rather,
the immune response is caught in a continuous loop of activation and inhibition. Experts from Charite' -- Universita"tsmedizin Berlin, the University of Bonn, the German Center for Neurodegenerative Diseases
(DZNE), the Helmholtz Centre for Infection Research (HZI) and the German
Center for Infection Research (DZIF), along with colleagues from a
nationwide research network, present these findings in the scientific
journal Cell.


==========================================================================
Most patients infected with the coronavirus SARS-CoV-2 show mild or
even no symptoms. However, 10 to 20 percent of those affected develop
pneumonia during the course of COVID-19 disease, some of them with life-threatening effects.

"There is still not very much known about the causes of these severe
courses of the disease. The high inflammation levels measured in those
affected actually indicate a strong immune response. Clinical findings, however, rather tend to indicate an ineffective immune response. This is
a contradiction," says Joachim Schultze, professor at the University of
Bonn and research group leader at the DZNE. "We therefore assume that
although immune cells are produced in large quantities, their function
is defective. That is why we examined the blood of patients with varying degrees of COVID-19 severity," explains Leif Erik Sander, Professor of Infection Immunology and Senior Physician Charite''s Medical Department, Division of Infectious Diseases and Respiratory Medicine.

High-precision methods The study was carried out within the framework
of a nationwide consortium - - the "German COVID-19 OMICS Initiative"
(DeCOI) -- resulting in the analysis and interpretation of the data
being spread across various teams and sites.

Joachim Schultze was significantly involved in coordinating the
project. The blood samples came from a total of 53 men and women
with COVID-19 from Berlin and Bonn, whose course of disease was
classified as mild or severe according to the World Health Organization classification. Blood samples from patients with other viral respiratory
tract infections as well as from healthy individuals served as important controls.

The investigations involved the use of single-cell OMICs technologies,
a collective term for modern laboratory methods that can be used
to determine, for example, the gene activity and the amount of
proteins on the level of single, individual cells -- thus with very
high resolution. Using this data, the scientists characterized the
properties of immune cells circulating in the blood -- so-called white
blood cells. "By applying bioinformatics methods on this extremely comprehensive data collection of the gene activity of each individual
cell, we could gain a comprehensive insight of the ongoing processes
in the white blood cells," explains Yang Li, Professor at the Centre
for Individualised Infection Medicine (CiiM) and Helmholtz Centre for
Infection Research (HZI) in Hannover. "In combination with the observation
of important proteins on the surface of immune cells, we were able to
decipher the changes in the immune system of patients with COVID-19,"
adds Birgit Sawitzki, Professor at the Institute of Medical Immunology
on Campus Virchow-Klinikum.

"Immature" cells The human immune system comprises a broad arsenal of
cells and other defense mechanisms that interact with each other. In the current study, the focus was on so-called myeloid cells, which include neutrophils and monocytes. These are immune cells that are at the very
front of the immune response chain, i.e. they are mobilized at a very
early stage to defend against infections. They also influence the later formation of antibodies and other cells that contribute to immunity. This
gives the myeloid cells a key position.



========================================================================== "With the so-called neutrophils and the monocytes we have found that these immune cells are activated, i.e. ready to defend the patient against
COVID-19 in the case of mild disease courses. They are also programmed
to activate the rest of the immune system. This ultimately leads to an effective immune response against the virus," explains Antoine-Emmanuel
Saliba, head of a research group at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Wu"rzburg.

But the situation is different in severe cases of COVID-19, explains
Sawitzki: "Here, neutrophils and monocytes are only partially activated
and they do not function properly. We find considerably more immature
cells that have a rather inhibitory effect on the immune response." Sander adds: "The phenomenon can also be observed in other severe infections,
although the reason for this is unclear. Many indications suggest
that the immune system stands in its own way during severe courses of
COVID-19. This could possibly lead to an insufficient immune response
against the corona virus, with a simultaneous severe inflammation in
the lung tissue." Approaches to therapy? The current findings could
point to new therapeutic options, says Anna Aschenbrenner from the LIMES Institute at the University of Bonn: "Our data suggest that in severe
cases of COVID-19, strategies should be considered that go beyond the
treatment of other viral diseases." The Bonn researcher says that in the
case of viral infections one does not actually want to suppress the immune system. "If, however, there are too many dysfunctional immune cells, as
our study shows, then one would very much like to suppress or reprogram
such cells." Jacob Nattermann, Professor at the Medical Clinic I of
the University Hospital Bonn and head of a research group at the DZIF,
further explains: "Drugs that act on the immune system might be able to
help. But this is a delicate balancing act. After all, it's not a matter
of shutting down the immune system completely, but only those cells that
slow down themselves, so to speak. In this case these are the immature
cells. Possibly we can learn from cancer research. There is experience
with therapies that target these cells." Nationwide team effort In view
of the many people involved, Schultze emphasizes the cooperation within
the research consortium: "As far as we know, this study is one of the most comprehensive studies to date on the immune response in COVID-19 based
on single cell data. The parallel analysis of two independent patient
cohorts is one of the strengths of our study. We analyzed patient cohorts
from two different sites using different methods and were thus able to
validate our findings directly. This is only possible if research data
is openly shared and cooperation is based on trust. This is extremely important, especially in the current crisis situation."

========================================================================== Story Source: Materials provided by DZNE_-_German_Center_for_Neurodegenerative_Diseases.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jonas Schulte-Schrepping, Nico Reusch, Daniela Paclik, Kevin
Bassler,
Stephan Schlickeiser, Bowen Zhang, Benjamin Kra"mer, Tobias
Krammer, Sophia Brumhard, Lorenzo Bonaguro, Elena De Domenico,
Daniel Wendisch, Martin Grasshoff, Theodore S. Kapellos, Michael
Beckstette, Tal Pecht, Adem Saglam, Oliver Dietrich, Henrik
E. Mei, Axel R. Schulz, Claudia Conrad, De'sire'e Kunkel, Ehsan
Vafadarnejad, Cheng-Jian Xu, Arik Horne, Miriam Herbert, Anna Drews,
Charlotte Thibeault, Moritz Pfeiffer, Stefan Hippenstiel, Andreas
Hocke, Holger Mu"ller-Redetzky, Katrin-Moira Heim, Felix Machleidt,
Alexander Uhrig, Laure Bosquillon de Jarcy, Linda Ju"rgens, Miriam
Stegemann, Christoph R. Glo"senkamp, Hans-Dieter Volk, Christine
Goffinet, Markus Landthaler, Emanuel Wyler, Philipp Georg, Maria
Schneider, Chantip Dang-Heine, Nick Neuwinger, Kai Kappert,
Rudolf Tauber, Victor Corman, Jan Raabe, Kim Melanie Kaiser,
Michael To Vinh, Gereon Rieke, Christian Meisel, Thomas Ulas,
Matthias Becker, Robert Geffers, Martin Witzenrath, Christian
Drosten, Norbert Suttorp, Christof von Kalle, Florian Kurth,
Kristian Ha"ndler, Joachim L. Schultze, Anna C.

Aschenbrenner, Yang Li, Jacob Nattermann, Birgit Sawitzki, Antoine-
Emmanuel Saliba, Leif Erik Sander. Severe COVID-19 is marked by a
dysregulated myeloid cell compartment. Cell, 2020; DOI: 10.1016/
j.cell.2020.08.001 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200806111822.htm

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