Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study

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 i...

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Vydáno v:Frontiers in immunology Ročník 11; s. 581338
Hlavní autoři: Notz, Quirin, Schmalzing, Marc, Wedekink, Florian, Schlesinger, Tobias, Gernert, Michael, Herrmann, Johannes, Sorger, Lena, Weismann, Dirk, Schmid, Benedikt, Sitter, Magdalena, Schlegel, Nicolas, Kranke, Peter, Wischhusen, Jörg, Meybohm, Patrick, Lotz, Christopher
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers Media S.A 06.10.2020
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ISSN:1664-3224, 1664-3224
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Abstract 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). This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14 and May 28 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. 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. 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.
AbstractList 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). This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14 and May 28 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. 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. 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.
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).ObjectivesThe 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).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.MethodsThis 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.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.ResultsAll 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.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.ConclusionsMassively 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.
ObjectivesThe 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).MethodsThis 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.ResultsAll 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.ConclusionsMassively 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.
Author Kranke, Peter
Meybohm, Patrick
Lotz, Christopher
Wedekink, Florian
Gernert, Michael
Schmalzing, Marc
Sorger, Lena
Notz, Quirin
Herrmann, Johannes
Schlegel, Nicolas
Schmid, Benedikt
Sitter, Magdalena
Schlesinger, Tobias
Weismann, Dirk
Wischhusen, Jörg
AuthorAffiliation 4 Department of Internal Medicine I, University Hospital Würzburg , Würzburg , Germany
1 Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg , Würzburg , Germany
5 Department of General, Visceral, Vascular and Pediatric Surgery (Surgery I), University Hospital Würzburg , Würzburg , Germany
3 Department of Gynecology, Section for Experimental Tumor Immunology, University Hospital Würzburg , Würzburg , Germany
2 Department of Medicine II, Rheumatology and Clinical Immunology, University Hospital Würzburg , Würzburg , Germany
AuthorAffiliation_xml – name: 3 Department of Gynecology, Section for Experimental Tumor Immunology, University Hospital Würzburg , Würzburg , Germany
– name: 2 Department of Medicine II, Rheumatology and Clinical Immunology, University Hospital Würzburg , Würzburg , Germany
– name: 4 Department of Internal Medicine I, University Hospital Würzburg , Würzburg , Germany
– name: 5 Department of General, Visceral, Vascular and Pediatric Surgery (Surgery I), University Hospital Würzburg , Würzburg , Germany
– name: 1 Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg , Würzburg , Germany
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  surname: Lotz
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ContentType Journal Article
Copyright Copyright © 2020 Notz, Schmalzing, Wedekink, Schlesinger, Gernert, Herrmann, Sorger, Weismann, Schmid, Sitter, Schlegel, Kranke, Wischhusen, Meybohm and Lotz.
Copyright © 2020 Notz, Schmalzing, Wedekink, Schlesinger, Gernert, Herrmann, Sorger, Weismann, Schmid, Sitter, Schlegel, Kranke, Wischhusen, Meybohm and Lotz 2020 Notz, Schmalzing, Wedekink, Schlesinger, Gernert, Herrmann, Sorger, Weismann, Schmid, Sitter, Schlegel, Kranke, Wischhusen, Meybohm and Lotz
Copyright_xml – notice: Copyright © 2020 Notz, Schmalzing, Wedekink, Schlesinger, Gernert, Herrmann, Sorger, Weismann, Schmid, Sitter, Schlegel, Kranke, Wischhusen, Meybohm and Lotz.
– notice: Copyright © 2020 Notz, Schmalzing, Wedekink, Schlesinger, Gernert, Herrmann, Sorger, Weismann, Schmid, Sitter, Schlegel, Kranke, Wischhusen, Meybohm and Lotz 2020 Notz, Schmalzing, Wedekink, Schlesinger, Gernert, Herrmann, Sorger, Weismann, Schmid, Sitter, Schlegel, Kranke, Wischhusen, Meybohm and Lotz
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Keywords Coronavirus Disease 2019
immune response
inflammation
Severe Acute Respiratory Syndrome Coronavirus 2
acute respiratory distress syndrome
cytokines
growth differentiation factor 15
Language English
License Copyright © 2020 Notz, Schmalzing, Wedekink, Schlesinger, Gernert, Herrmann, Sorger, Weismann, Schmid, Sitter, Schlegel, Kranke, Wischhusen, Meybohm and Lotz.
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This article was submitted to Inflammation, a section of the journal Frontiers in Immunology
Edited by: Rudolf Lucas, Augusta University, United States
Reviewed by: Juerg Hamacher, Lindenhofspital, Switzerland; Daniel Scott-Algara, Institut Pasteur, France
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Snippet The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and...
ObjectivesThe severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts...
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StartPage 581338
SubjectTerms acute respiratory distress syndrome
Aged
Antibodies, Viral - blood
Antibodies, Viral - immunology
Betacoronavirus - immunology
Coronavirus Disease 2019
Coronavirus Infections - immunology
Coronavirus Infections - pathology
COVID-19
Cytokine Release Syndrome - immunology
Cytokine Release Syndrome - pathology
cytokines
Female
growth differentiation factor 15
Growth Differentiation Factor 15 - blood
Humans
Immunoglobulin G - blood
Immunoglobulin G - immunology
Immunology
inflammation
Intensive Care Units
Interleukin-10 - blood
Interleukin-6 - blood
Longitudinal Studies
Lymphopenia
Male
Middle Aged
Pandemics
Pilot Projects
Pneumonia, Viral - immunology
Pneumonia, Viral - pathology
Retrospective Studies
SARS-CoV-2
Severe Acute Respiratory Syndrome - immunology
Severe Acute Respiratory Syndrome - pathology
Severe Acute Respiratory Syndrome Coronavirus 2
Spike Glycoprotein, Coronavirus - immunology
Title Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study
URI https://www.ncbi.nlm.nih.gov/pubmed/33123167
https://www.proquest.com/docview/2456412488
https://pubmed.ncbi.nlm.nih.gov/PMC7573122
https://doaj.org/article/fc6ae42247bc4059900b487c18998031
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