The Expression of Fibrogenic Cytokines by Human Peripheral Blood Mononuclear Cells in Response to SARS-CoV-2 Spike Protein

Abstract

SARS-CoV-2, a single stranded positive RNA-virus, emerged in 2019 and caused a global pandemic. Some infected patients develop severe complications, such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. The mechanisms leading to lung fibrosis in the context of COVID-19 are still unclear. However, there are correlations between this condition and certain inflammatory mediators that are elevated in the plasma of patients. This study addressed the question of whether SARS-CoV-2 spike protein was able to directly activate immune cells to produce inflammatory and fibrogenic cytokines, independent of viral infection. By stimulating peripheral blood mononuclear cells (PBMC) from healthy blood donors through different formulations of SARS-CoV-2 spike protein, the expression of fibrogenic and inflammatory cytokines was measured. The spike protein induced a significantly increased expression of IL-1β and IL-6 mRNA in PBMC. Both cytokines are important players in the COVID-19 cytokine storm, in ARDS and in the development of pulmonary fibrosis. Different receptors with an affinity to the spike protein may be involved. However, the exact mechanism on how the spike protein leads to a higher cytokine expression in PBMC needs further investigation.