SARS-CoV-2 infection- induced growth factors play differential roles in COVID-19 pathogenesis

AIMS: Biologically active molecules cytokines and growth factors (GFs) are critical regulators of tissue injury/repair and emerge as key players in COVID-19 pathophysiology. However, specific disease stage of GFs dysregulation and, whether these GFs have associations with thromboembolism and tissue injury/repair in COVID-19 remain vague. MAIN METHODS: GF profiling in hospitalized moderate (non-ICU) and critically ill (ICU) COVID-19 patients was performed through legendPlex assay. KEY FINDINGS: Investigation revealed profound elevation of VEGF, PDGFs, EGF, TGF-α, FGF-basic, and erythropoietin (EPO) in moderate cases and decline or trend of decline with disease advancement. We found strong positive correlations of plasma VEGF, PDGFs, and EPO with endothelial dysfunction markers P-selectin and sCD40L. Interestingly, the HGF and G-CSF were upregulated at the moderate stage and remained elevated at the severe stage of COVID-19. Moreover, strong negative correlations of PDGFs (r(2) = 0.238, P = 0.006), EPO (r(2) = 0.18, P = 0.01) and EGF (r(2) = 0.172, P = 0.02) and positive correlation of angiopoietin-2 (r(2) = 0.267, P = 0.003) with D-dimer, a marker of thromboembolism, was observed. Further, plasma PDGFs (r(2) = 0.199, P = 0.01), EPO (r(2) = 0.115, P = 0.02), and EGF (r(2) = 0.108, P = 0.07) exhibited negative correlations with tissue injury marker, myoglobin. SIGNIFICANCE: Taken together, unlike cytokines, most of the assessed GFs were upregulated at the moderate stage of COVID-19. The induction of GFs likely occurs due to endothelial dysfunction and may counter the adverse effects of cytokine storms which is reflected by inverse correlations of PDGFs, EPO, and EGF with thromboembolism and tissue injury markers. The findings suggest that the assessed GFs play differential roles in the pathogenesis of COVID-19.