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Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study.
Front Immunol. 2020; 11:581338.FI

Abstract

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.

Authors+Show Affiliations

Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.Department of Medicine II, Rheumatology and Clinical Immunology, University Hospital Würzburg, Würzburg, Germany.Department of Gynecology, Section for Experimental Tumor Immunology, University Hospital Würzburg, Würzburg, Germany.Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.Department of Medicine II, Rheumatology and Clinical Immunology, University Hospital Würzburg, Würzburg, Germany.Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.Department of Gynecology, Section for Experimental Tumor Immunology, University Hospital Würzburg, Würzburg, Germany.Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.Department of General, Visceral, Vascular and Pediatric Surgery (Surgery I), University Hospital Würzburg, Würzburg, Germany.Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.Department of Gynecology, Section for Experimental Tumor Immunology, University Hospital Würzburg, Würzburg, Germany.Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

33123167

Citation

Notz, Quirin, et al. "Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study." Frontiers in Immunology, vol. 11, 2020, p. 581338.
Notz Q, Schmalzing M, Wedekink F, et al. Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study. Front Immunol. 2020;11:581338.
Notz, Q., Schmalzing, M., Wedekink, F., Schlesinger, T., Gernert, M., Herrmann, J., Sorger, L., Weismann, D., Schmid, B., Sitter, M., Schlegel, N., Kranke, P., Wischhusen, J., Meybohm, P., & Lotz, C. (2020). Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study. Frontiers in Immunology, 11, 581338. https://doi.org/10.3389/fimmu.2020.581338
Notz Q, et al. Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study. Front Immunol. 2020;11:581338. PubMed PMID: 33123167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study. AU - Notz,Quirin, AU - Schmalzing,Marc, AU - Wedekink,Florian, AU - Schlesinger,Tobias, AU - Gernert,Michael, AU - Herrmann,Johannes, AU - Sorger,Lena, AU - Weismann,Dirk, AU - Schmid,Benedikt, AU - Sitter,Magdalena, AU - Schlegel,Nicolas, AU - Kranke,Peter, AU - Wischhusen,Jörg, AU - Meybohm,Patrick, AU - Lotz,Christopher, Y1 - 2020/10/06/ PY - 2020/07/08/received PY - 2020/09/21/accepted PY - 2020/10/30/entrez PY - 2020/10/31/pubmed PY - 2020/11/11/medline KW - Coronavirus Disease 2019 KW - Severe Acute Respiratory Syndrome Coronavirus 2 KW - acute respiratory distress syndrome KW - cytokines KW - growth differentiation factor 15 KW - immune response KW - inflammation SP - 581338 EP - 581338 JF - Frontiers in immunology JO - Front Immunol VL - 11 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. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/33123167/Pro__and_Anti_Inflammatory_Responses_in_Severe_COVID_19_Induced_Acute_Respiratory_Distress_Syndrome_An_Observational_Pilot_Study_ L2 - https://doi.org/10.3389/fimmu.2020.581338 DB - PRIME DP - Unbound Medicine ER -