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 th and May 28 th 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.
【저자키워드】 severe acute respiratory syndrome coronavirus 2, Inflammation, Coronavirus disease 2019, immune response, Cytokines, acute respiratory distress syndrome, growth differentiation factor 15, 【초록키워드】 COVID-19, SARS-CoV-2, IgM, Resilience, ARDS, intensive care, Anti-inflammatory, spike, IL-6, severity, Antibody Response, NK cell, CD8+ T cells, Lymphocyte subsets, coronavirus 2, ICU, Receptor binding domain, B cell, Lymphocyte count, Retrospective study, Protein, interleukin, Immunoglobulin, RBD, lymphocytopenia, Patient, IL-10, respiratory, longitudinal, mechanism, T helper cells, cellular response, acute respiratory distress, Interaction, antibody production, B cell response, natural killer, tissue, growth, ICU treatment, severe ARDS, slight increase, syndrome, naïve, single-center, routine clinical care, immune defense, CD8+, flow-cytometry, Cytokine analysis, anti-inflammatory cytokine, objective, decrease, Result, analyzed, collected, died, elevated, characterized, suffered, upregulated, 【제목키워드】 response, respiratory, Pro,