In vitro, overexpression of the SARS-CoV-2 spike protein in the HEK293 cell line, which exhibits epithelial morphology, led to increased production of myofibroblast markers, including α-SMA and collagen type I. In vivo, injection of the SARS-CoV-2 spike protein in BLM-induced SSc mice resulted in the secretion of spike protein and anti-phospholipid antibody, akin to what has been observed in individuals infected with COVID-19. Here, ACTA1 is linked to systemic sclerosis.