• 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, and Christopher Lotz.
• Department of Anesthesiology and Intensive Care Medicine, University Hospital Würzburg, Würzburg, Germany.
• Front Immunol. 2020 Jan 1; 11: 581338.

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.Copyright © 2020 Notz, Schmalzing, Wedekink, Schlesinger, Gernert, Herrmann, Sorger, Weismann, Schmid, Sitter, Schlegel, Kranke, Wischhusen, Meybohm and Lotz.

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