Cytokine Profiling in Different SARS-CoV-2 Genetic Variants

Abstract

This study is a successor of our previous work concerning changes in the chemokine profile in infection that are associated with different SARS-CoV-2 genetic variants. The goal of our study was to take into account both the virus and the host immune system by assessing concentrations of cytokines in patients infected with different SARS-CoV-2 variants (ancestral Wuhan strain, Alpha, Delta and Omicron). Our study was performed on 340 biological samples taken from COVID-19 patients and healthy donors in the timespan between May 2020 and April 2022. We performed genotyping of the virus in nasopharyngeal swabs, which was followed by assessment of cytokines' concentration in blood plasma. We noted that out of nearly 30 cytokines, only four showed stable elevation independently of the variant (IL-6, IL-10, IL-18 and IL-27), and we believe them to be 'constant' markers for COVID-19 infection. Cytokines that were studied as potential biomarkers lose their diagnostic value as the virus evolves, and the specter of potential targets for predictive models is narrowing. So far, only four cytokines (IL-6, IL-10, IL-18, and IL-27) showed a consistent rise in concentrations independently of the genetic variant of the virus. Although we believe our findings to be of scientific interest, we still consider them inconclusive; further investigation and comparison of immune responses to different variants of SARS-CoV-2 is required.

Keywords: COVID-19; cytokines; multiplex analysis; variants of concern.

Figure 1

Concentrations of type I receptor family (IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-15, IL-27, GM-CSF, G-CSF) in plasma samples from patients infected with different variants of SARS-CoV-2: the original Wuhan strain (n = 59), the Alpha variant (n = 95), the Delta variant (n = 78) or the Omicron variant (n = 57). Note: Cytokine comparison was performed based on disease severity (moderate, severe) of COVID-19. The green horizontal stripe represents interquartile range (Q25–Q75) for healthy donors (n = 51). The color red highlights groups that show statistically significant differences in comparison with healthy donors. Comparative analysis was performed with one-way ANOVA.

Figure 2

Concentrations of type II receptor family (IL-10, IL-22, IFNα and IFNγ; TNFα, TNFβ) in plasma samples from patients infected with different variants of SARS-CoV-2: the original Wuhan strain (n = 59), the Alpha variant (n = 95), the Delta variant (n = 78) or the Omicron variant (n = 57).

Figure 3

Concentrations of immunoglobulin superfamily cytokines/growth factors (IL-1α, IL-1β, IL-1RA, IL-18, M-CSF, PDGF-AA, PDGF-AA/BB) in plasma samples from patients infected with different variants of SARS-CoV-2: the original Wuhan strain (n = 59), the Alpha variant (n = 95), the Delta variant (n = 78), or the Omicron variant (n = 57). See notes for Figure 1.

Figure 4

Concentrations of growth factors (IL-17A, EGF, FGF-2/FGF-basic, Flt3 Ligand, TGF-α and VEGF-A) in plasma samples from patients infected with different variants of SARS-CoV-2: the original Wuhan strain (n = 59), the Alpha variant (n = 95), the Delta variant (n = 78) or the Omicron variant (n = 57). See notes for Figure 1.

Figure 5

Spectrum of cytokines showing statistically significant (p < 0.01) changes in comparison with healthy donors cohort (n = 51). Each color represents one of the four variants of concern of SARS-CoV-2 (blue for the original Wuhan strain, green for the Alpha variant, gray for the Delta variant, and red for the Omicron variant).