SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis

• Published in: Cell communication and signaling 2023-03, Vol.21 (1), p.44-44, Article 44
• Main Authors: Lee, A Ram, Woo, Jin Seok, Lee, Seon-Yeong, Lee, Yeon Su, Jung, Jooyeon, Lee, Chae Rim, Park, Sung-Hwan, Cho, Mi-La
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Ankle; Antibodies; Antiphospholipid antibodies; Arthritis, Experimental; Arthritis, Rheumatoid; Autoantibodies; Autoimmune disease; Autoimmune diseases; Cell culture; Chemokines; Collagen; Coronavirus disease 2019 (COVID-19); Coronaviruses; COVID-19; COVID-19 diagnostic tests; COVID-19 vaccines; CXC chemokines; Cytokines; Disease; Enzymes; Flow cytometry; Government agencies; Humans; Immunization; Inflammation; Laboratories; Mice; Phospholipids; Plasmids; Proteins; Pulmonary embolisms; Rheumatoid arthritis; Rheumatoid arthritis (RA); SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Spike protein; Synoviocytes; Thromboembolism; Thrombosis
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-023-01044-0

Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood. This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model. Human fibroblast-like synoviocytes (FLS) were transduced with lentivirus carrying the SARS-CoV-2 spike protein gene in vitro, and the levels of inflammatory cytokine and chemokine expression were measured. For in vivo experiments, CIA mice were injected with the gene encoding SARS-CoV-2 spike protein, and disease severity, levels of autoantibodies, thrombotic factors, and inflammatory cytokine and chemokine expression were assessed. In the in vitro experiments, the levels of inflammatory cytokine and chemokine expression were significantly increased by overexpression of SARS-CoV-2 spike protein in human FLS. The incidence and severity of RA in CIA mice were slightly increased by SARS-CoV-2 spike protein in vivo. In addition, the levels of autoantibodies and thrombotic factors, such as anti-CXC chemokine ligand 4 (CXCL4, also called PF4) antibodies and anti-phospholipid antibodies were significantly increased by SARS-CoV-2 spike protein. Furthermore, tissue destruction and inflammatory cytokine level in joint tissue were markedly increased in CIA mice by SARS-CoV-2 spike protein. The results of the present study suggested that COVID-19 accelerates the development and progression of RA by increasing inflammation, autoantibody production, and thrombosis. Video Abstract.