Predictive value of specific cytokines for lethal COVID-19 outcome

Abstract

In our study, we aimed to evaluate the significance of specific cytokines in blood plasma as predictive markers of COVID-associated mortality. Materials and methods. In plasma samples of 29 patients with PCR-confirmed COVID-19 we measured the concentrations of 47 molecules. These molecules included: interleukins and selected pro-inflammatory cytokines (IL-1, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL 13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFN2, IFN, TNF, TNF/Lymphotoxin-(LTA)); chemokines (CCL2/MCP-1, CCL3/MIP-1, CCL4/MIP-1, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GRO, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine); anti-inflammatory cytokines (IL-1Ra, IL-10); growth factors (EGF, FGF-2/FGF-basic, Flt-3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGFAB/BB, TGF, VEGF-A); and sCD40L. We used multiplex analysis based on xMAP technology (Luminex, USA) using Luminex MagPix. As controls, we used plasma samples of 20 healthy individuals. Based on the results, we applied Receiver Operating Characteristic (ROC) analysis and Area Under Curve (AUC) values to compare two different predictive tests and to choose the optimal division point for disease outcome (survivors/non-survivors). To find optimal biomarker combinations, we as used cytokines concentrations as dependent variables to grow a regression tree using JMP 16 Software.Results. Out of 47 studied cytokines/chemokines/growth factors, we picked four pro-inflammatory cytokines as having high significance in evaluation of COVID-19 outcome: IL-6, IL-8, IL-15, and IL-18. Based on the results received, we assume that the highest significance in terms of predicting the outcome of acute COVID-19 belongs to IL-6 and IL-18. Conclusion. Analyzing concentrations of IL-6 and IL-18 before administering treatment may prove valuable in terms of outcome prognosis.

Role of IL-27 in COVID-19: A Thin Line Between Protection and Disease Promotion

“…Our research showed that there was a significant increase in concentrations among both COVID-19 survivors and non-survivors when compared to healthy individuals. However, there was no statistical significance found when comparing the survivors and non-survivors [46]. And while it is possible that IL-27 may have predictive value, our analysis showed no sufficient sensitivity or specificity to support this claim.…”

Macrophage-Derived Chemokine MDC/CCL22: An Ambiguous Finding in COVID-19

“…As the pandemic progressed, newer points of interest emerged: for instance, we investigated the value of cytokine profiling in acute infection and persisting patterns in convalescent patients [21]. We also explored predictors of disease severity among cytokines/chemokines [22], and we suggested a model for prognosis of the disease outcome. However, as the virus changed, we have realized that the immunological landscape went through certain changes as well.…”

MDC/CCL22 depletion in COVID-19 and post-COVID

“…Specifically, researchers highlighted a significant shortage of DCs in COVID-19 patients, both in acute and post-recovery periods. Moreover, other studies have highlighted the relationship between disease severity [2] and dendritic cell properties [5], both quantitative and qualitative. This, however, for some reason does not affect other cytokines and chemokines, produced by DCs (IL-1α, IL-1β, IL-6, IL-7, IL-12 (p35 and p40), IL-15, IL-18, TNFα, TGF-β, macrophage CSF, and granulocytemacrophage CSF, but not IL-2, IL-3, IL-4, IL-5, IL-9, and IFNγ transcripts).…”