TY  - JOUR
A1  - Notz, Quirin
A1  - Schmalzing, Marc
A1  - Wedekink, Florian
A1  - Schlesinger, Tobias
A1  - Gernert, Michael
A1  - Herrmann, Johannes
A1  - Sorger, Lena
A1  - Weismann, Dirk
A1  - Schmid, Benedikt
A1  - Sitter, Magdalena
A1  - Schlegel, Nicolas
A1  - Kranke, Peter
A1  - Wischhusen, Jörg
A1  - Meybohm, Patrick
A1  - Lotz, Christopher
T1  - Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study
JF  - Frontiers in Immunology
N2  - Objectives
The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS).


Methods
This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed.


Results
All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment.


Conclusions
Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.
KW  - Coronavirus Disease 2019
KW  - acute respiratory distress syndrome
KW  - Severe Acute Respiratory Syndrome Coronavirus 2
KW  - cytokines
KW  - inflammation
KW  - growth differentiation factor 15
KW  - immune response
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212815
SN  - 1664-3224
VL  - 11
ER  -