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...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1818230296345051136 |
---|---|
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. |
first_indexed | 2024-12-12T10:32:14Z |
format | Article |
id | doaj.art-fc6ae42247bc4059900b487c18998031 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-12-12T10:32:14Z |
publishDate | 2020-10-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
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 |
work_keys_str_mv | AT quirinnotz proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT marcschmalzing proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT florianwedekink proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT tobiasschlesinger proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT michaelgernert proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT johannesherrmann proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT lenasorger proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT dirkweismann proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT benediktschmid proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT magdalenasitter proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT nicolasschlegel proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT peterkranke proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT jorgwischhusen proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT patrickmeybohm proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy AT christopherlotz proandantiinflammatoryresponsesinseverecovid19inducedacuterespiratorydistresssyndromeanobservationalpilotstudy |