Publication

Abstract :

Background and objectives

Coronavirus disease (COVID-19) exhibits a range of clinical symptoms, including viral pneumonia, which can progress to acute respiratory distress syndrome, substantial alveolar destruction, and even multi-organ failure in severe cases. Disease pathology is greatly influenced by the host immune response. Several studies reported the perturbation of T-cell responses in COVID-19 patients. Activation and differentiation of CD4+ T cells into various subsets depend on the expression of lineage-specific transcription factors and overall cytokine milieu. Hence, a thorough evaluation of T helper cell lineage-specific transcription factors and pro-inflammatory cytokines can provide crucial insight into COVID-19 pathogenesis and may aid in developing strategies to prevent disease severity. Here, we performed a cross-sectional study to delineate the dysfunctional T helper cell subset immune response associated with COVID-19 disease severity.

Methods

We assessed T helper cell responses in SARS-CoV-2 infected individuals who presented with either asymptomatic, mild, or severe disease. mRNA profiling of lineage specific transcription factors and associated cytokines was done using real-time qPCR. Cytokine profiling was done using ELISA.

Results

mRNA levels of FOXP-3 were significantly decreased in patients with severe COVID-19. No significant difference was observed for T-bet and GATA-3 among all of the groups. Bcl-6, the transcription factor for Tfh cell subsets, showed an increased trend in its association with disease progression. Furthermore, mRNA levels of IL-21 were significantly increased with disease severity. We also observed a significant increase in the concentration of pro-inflammatory cytokines IL-6 and IL-1β in patients with severe COVID-19.

Conclusions

These findings provide new insight into COVID-19 disease pathology and may aid in developing effective strategies to manage/control disease severity.