Th-1, Th-2, Th-9, Th-17, Th-22 type cytokine concentrations of critical COVID-19 patients after treatment with Remdesivir

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the world causing a pandemic known as coronavirus disease 2019 (COVID-19). Cytokine storm was directly correlated with severity of COVID-19 syndromes. We evaluated the levels of 13 cytokines in ICU hospitalized COVID-19 patients (n = 29) before, and after treatment with Remdesivir as well as in healthy controls (n = 29). Blood samples were obtained from ICU patients during ICU admission (before treatment) and 5 days after treatment with Remdesivir. A group of 29 age- and gender-matched healthy controls was also studied. Cytokine levels were evaluated by multiplex immunoassay method using a fluorescence labeled cytokine panel. In comparison to cytokine levels measured at ICU admission, serum levels were reduced of IL-6 (134.75 pg/mL vs. 20.73 pg/mL, P < 0.0001), TNF-α (121.67 pg/mL vs. 10.15 pg/mL, P < 0.0001) and IFN-γ (29.69 pg/mL vs. 22.27 pg/mL, P = 0.005), whereas serum level was increased of IL-4 (8.47 pg/mL vs. 12.44 pg/mL, P = 0.002) within 5 days after Remdesivir treatment. Comparing with before treatment, Remdesivir significantly reduced the levels of inflammatory (258.98 pg/mL vs. 37.43 pg/mL, P < 0.0001), Th1-type (31.24 pg/mL vs. 24.46 pg/mL, P = 0.007), and Th17-type (36.79 pg/mL vs. 26.22 pg/mL, P < 0.0001) cytokines in critical COVID-19 patients. However, after Remdesivir treatment, the concentrations of Th2-type cytokines were significantly higher than before treatment (52.69 pg/mL vs. 37.09 pg/mL, P < 0.0001). In conclusion, Remdesivir led to decrease levels of Th1-type and Th17-type cytokines and increase Th2-type cytokines in critical COVID-19 patients 5 days after treatment.

Keywords: COVID-19; Critical COVID-19 patients; Cytokines storm; Inflammatory cytokines; Remdesivir treatment; SARS-CoV-2; Th1-type cytokines; Th17-type cytokines; Th2-type cytokines.

Fig. 1

Comparison of individual serum cytokines between healthy controls and critical COVID-19 patients. Data are presented as median and analyzed by Kruskal-Wallis test followed by Bonferroni and Wilcoxon rank-sum tests; *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001.

Fig. 2

Comparison of serum inflammatory (IL-6 plus TNF-α), Th1-type (IL-2 plus IFN-γ), Th2-type (IL-4 plus IL-5 plus IL-9 plus IL-13), Th17-type (IL-17F plus IL-17A plus IL-21 plus IL-22) and anti-inflammatory (IL-10) cytokines between healthy controls and critical COVID-19 patients. Data are presented as median and analyzed by Kruskal-Wallis test followed by Bonferroni and Wilcoxon rank-sum tests;*P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001.

Fig. 3

Correlation analysis of the different cytokines profiles with each other in all study groups. (A) Heat map correlation of cytokines profiles with each other in healthy controls, (B) Heat map correlation of cytokines profiles with each other in critical COVID-19 patients before treatment with Remdesivir, (C) Heat map correlation of cytokines profiles with each other in critical COVID-19 patients after treatment with Remdesivir. Based on the guide of the heat map, the red color of cells shows the negative correlation between determined cytokine profiles. In addition, the blue color demonstrates the existence of positive correlation. The intensity of colors is directly related to the value of correlation coefficient (r) and its closeness to −1 (perfectly linear negative correlation) and +1 (perfectly linear positive correlation). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)