Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19. Herr, C., Mang, S., Mozafari, B., Guenther, K., Speer, T., Seibert, M., Srikakulam, S. K., Beisswenger, C., Ritzmann, F., Keller, A., Müller, R., Smola, S., Eisinger, D., Zemlin, M., Danziger, G., Volk, T., Hörsch, S., Krawczyk, M., Lammert, F., Adams, T., Wagenpfeil, G., Kindermann, M., Marcu, C., Ataya, Z. W. D., Mittag, M., Schwarzkopf, K., Custodis, F., Grandt, D., Schaefer, H., Eltges, K., Lepper, P. M, & Bals, R. Journal of Inflammation Research, Volume 14:4651-4667, 09, 2021.
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Background: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. Patients and methods: Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. Results: The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). Discussion: Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

@article{herr532513421,
    author = {Herr, Christian and Mang, Sebastian and Mozafari, Bahareh and Guenther, Katharina and Speer, Thimoteus and Seibert, Martina and Srikakulam, Sanjay Kumar and Beisswenger, Christoph and Ritzmann, Felix and Keller, Andreas and Müller, Rolf and Smola, Sigrun and Eisinger, Dominic and Zemlin, Michael and Danziger, Guy and Volk, Thomas and Hörsch, Sabrina and Krawczyk, Marcin and Lammert, Frank and Adams, Thomas and Wagenpfeil, Gudrun and Kindermann, Michael and Marcu, Constantin and Ataya, Zuhair Wolf Dietrich and Mittag, Marc and Schwarzkopf, Konrad and Custodis, Florian and Grandt, Daniel and Schaefer, Harald and Eltges, Kai and Lepper, Philipp M and Bals, Robert},
    year = {2021},
    month = {09},
    pages = {4651-4667},
    abstract = {Background: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. Patients and methods: Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. Results: The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). Discussion: Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.},
    title = {Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19},
    volume = {Volume 14},
    journal = {Journal of Inflammation Research},
    doi = {10.2147/JIR.S320685}
}

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