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  - 
TY  - JOUR
A1  - Notz, Quirin
A1  - Herrmann, Johannes
A1  - Schlesinger, Tobias
A1  - Helmer, Philipp
A1  - Sudowe, Stephan
A1  - Sun, Qian
A1  - Hackler, Julian
A1  - Roeder, Daniel
A1  - Lotz, Christopher
A1  - Meybohm, Patrick
A1  - Kranke, Peter
A1  - Schomburg, Lutz
A1  - Stoppe, Christian
T1  - Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS
JF  - Nutrients
N2  - The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = −0.495), PCT (r\(_s\) = −0.413), IL-6 (r\(_s\) = −0.429), IL-1β (r\(_s\) = −0.440) and IL-10 (r\(_s\) = −0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.
KW  - acute respiratory distress syndrome
KW  - selen
KW  - zinc
KW  - critical care
KW  - oxidative stress
KW  - nutrient supplementation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241112
SN  - 2072-6643
VL  - 13
IS  - 6
ER  -