SARS-CoV-2 causes periodontal fibrosis by deregulating mitochondrial beta-oxidation (preprint)

ABSTRACT

The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus mutate predominantly in the spike proteins, whilst the other key viral components remain stable. Previous studies have shown that the human oral cavity can potentially act as reservoir of the SARS-CoV-2 virus and COVID-19 is likely to be connected with poor periodontal health. However, the consequence of SARS-CoV-2 viral infection on human oral health has not been systematically examined. In this research, we aimed to study the pathogenicity of SARS-CoV-2 viral components on human periodontal health. We found that human periodontal tissues, particularly the fibroblasts highly expressed ACE2 and TMPRSS2. Exposure to SARS-CoV-2, especially by the viral envelope and membrane proteins induced fibrotic pathogenic phenotypes, including periodontal fibroblast hyperproliferation, concomitant with increased apoptosis and senescence. The fibrotic degeneration was mediated by a down-regulation of mitochondrial {beta}-oxidation. Fatty acid beta-oxidation inhibitor, etomoxir treatment could mirror the same pathological consequence on the fibroblasts, similar to SARS-CoV-2 infection. Our results therefore provide novel mechanistic insights into how SARS-CoV-2 infection can affect human periodontal health at the cell and molecular level.