tetano
Editor, Senior Moderator
Front Immunol
. 2020 Oct 6;11:581338.
doi: 10.3389/fimmu.2020.581338. eCollection 2020.
Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study
Quirin Notz[SUP] 1 [/SUP], Marc Schmalzing[SUP] 2 [/SUP], Florian Wedekink[SUP] 3 [/SUP], Tobias Schlesinger[SUP] 1 [/SUP], Michael Gernert[SUP] 2 [/SUP], Johannes Herrmann[SUP] 1 [/SUP], Lena Sorger[SUP] 3 [/SUP], Dirk Weismann[SUP] 4 [/SUP], Benedikt Schmid[SUP] 1 [/SUP], Magdalena Sitter[SUP] 1 [/SUP], Nicolas Schlegel[SUP] 5 [/SUP], Peter Kranke[SUP] 1 [/SUP], J?rg Wischhusen[SUP] 3 [/SUP], Patrick Meybohm[SUP] 1 [/SUP], Christopher Lotz[SUP] 1 [/SUP]
Affiliations
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 14[SUP]th[/SUP] and May 28[SUP]th[/SUP] 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 na?ve 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.
Keywords: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2; acute respiratory distress syndrome; cytokines; growth differentiation factor 15; immune response; inflammation.
. 2020 Oct 6;11:581338.
doi: 10.3389/fimmu.2020.581338. eCollection 2020.
Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study
Quirin Notz[SUP] 1 [/SUP], Marc Schmalzing[SUP] 2 [/SUP], Florian Wedekink[SUP] 3 [/SUP], Tobias Schlesinger[SUP] 1 [/SUP], Michael Gernert[SUP] 2 [/SUP], Johannes Herrmann[SUP] 1 [/SUP], Lena Sorger[SUP] 3 [/SUP], Dirk Weismann[SUP] 4 [/SUP], Benedikt Schmid[SUP] 1 [/SUP], Magdalena Sitter[SUP] 1 [/SUP], Nicolas Schlegel[SUP] 5 [/SUP], Peter Kranke[SUP] 1 [/SUP], J?rg Wischhusen[SUP] 3 [/SUP], Patrick Meybohm[SUP] 1 [/SUP], Christopher Lotz[SUP] 1 [/SUP]
Affiliations
- PMID: 33123167
- PMCID: PMC7573122
- DOI: 10.3389/fimmu.2020.581338
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 14[SUP]th[/SUP] and May 28[SUP]th[/SUP] 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 na?ve 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.
Keywords: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2; acute respiratory distress syndrome; cytokines; growth differentiation factor 15; immune response; inflammation.