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

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 r...

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Main Authors: Quirin Notz, Marc Schmalzing, Florian Wedekink, Tobias Schlesinger, Michael Gernert, Johannes Herrmann, Lena Sorger, Dirk Weismann, Benedikt Schmid, Magdalena Sitter, Nicolas Schlegel, Peter Kranke, Jörg Wischhusen, Patrick Meybohm, Christopher Lotz
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2020.581338/full
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author Quirin Notz
Marc Schmalzing
Florian Wedekink
Tobias Schlesinger
Michael Gernert
Johannes Herrmann
Lena Sorger
Dirk Weismann
Benedikt Schmid
Magdalena Sitter
Nicolas Schlegel
Peter Kranke
Jörg Wischhusen
Patrick Meybohm
Christopher Lotz
author_facet Quirin Notz
Marc Schmalzing
Florian Wedekink
Tobias Schlesinger
Michael Gernert
Johannes Herrmann
Lena Sorger
Dirk Weismann
Benedikt Schmid
Magdalena Sitter
Nicolas Schlegel
Peter Kranke
Jörg Wischhusen
Patrick Meybohm
Christopher Lotz
author_sort Quirin Notz
collection DOAJ
description 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.
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spelling doaj.art-fc6ae42247bc4059900b487c189980312022-12-22T00:27:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.581338581338Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot StudyQuirin Notz0Marc Schmalzing1Florian Wedekink2Tobias Schlesinger3Michael Gernert4Johannes Herrmann5Lena Sorger6Dirk Weismann7Benedikt Schmid8Magdalena Sitter9Nicolas Schlegel10Peter Kranke11Jörg Wischhusen12Patrick Meybohm13Christopher Lotz14Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, GermanyDepartment of Medicine II, Rheumatology and Clinical Immunology, University Hospital Würzburg, Würzburg, GermanyDepartment of Gynecology, Section for Experimental Tumor Immunology, University Hospital Würzburg, Würzburg, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, GermanyDepartment of Medicine II, Rheumatology and Clinical Immunology, University Hospital Würzburg, Würzburg, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, GermanyDepartment of Gynecology, Section for Experimental Tumor Immunology, University Hospital Würzburg, Würzburg, GermanyDepartment of Internal Medicine I, University Hospital Würzburg, Würzburg, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, GermanyDepartment of General, Visceral, Vascular and Pediatric Surgery (Surgery I), University Hospital Würzburg, Würzburg, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, GermanyDepartment of Gynecology, Section for Experimental Tumor Immunology, University Hospital Würzburg, Würzburg, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, GermanyObjectivesThe 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.581338/fullCoronavirus Disease 2019acute respiratory distress syndromeSevere Acute Respiratory Syndrome Coronavirus 2cytokinesinflammationgrowth differentiation factor 15
spellingShingle Quirin Notz
Marc Schmalzing
Florian Wedekink
Tobias Schlesinger
Michael Gernert
Johannes Herrmann
Lena Sorger
Dirk Weismann
Benedikt Schmid
Magdalena Sitter
Nicolas Schlegel
Peter Kranke
Jörg Wischhusen
Patrick Meybohm
Christopher Lotz
Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study
Frontiers in Immunology
Coronavirus Disease 2019
acute respiratory distress syndrome
Severe Acute Respiratory Syndrome Coronavirus 2
cytokines
inflammation
growth differentiation factor 15
title Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study
title_full Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study
title_fullStr Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study
title_full_unstemmed Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study
title_short Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study
title_sort pro and anti inflammatory responses in severe covid 19 induced acute respiratory distress syndrome an observational pilot study
topic Coronavirus Disease 2019
acute respiratory distress syndrome
Severe Acute Respiratory Syndrome Coronavirus 2
cytokines
inflammation
growth differentiation factor 15
url https://www.frontiersin.org/article/10.3389/fimmu.2020.581338/full
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