Contribution of STAT3 to the pathogenesis of COVID-19

• Published in: Microbial pathogenesis 2021-05, Vol.154, p.104836-104836, Article 104836
• Main Authors: Jafarzadeh, Abdollah, Nemati, Maryam, Jafarzadeh, Sara
• Format: Article
• Language: English
• Subjects: Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Cytokines - metabolism; Humans; Immune response; Inflammation; Pathogenesis; SARS-CoV-2; STAT3; STAT3 Transcription Factor; Treatment
• ISSN: 0882-4010; 1096-1208; 1096-1208
• DOI: 10.1016/j.micpath.2021.104836

Hyper-inflammatory responses, lymphopenia, unbalanced immune responses, cytokine storm, large viral replication and massive cell death play fundamental roles in the pathogenesis of COVID-19. Extreme production of many kinds of pro-inflammatory cytokines and chemokines occur in severe COVID-19 that called cytokine storm. Signal transducer and activator of transcription-3 (STAT-3) present in the cytoplasm in an inactive form and can be stimulated by a vast range of cytokines, chemokines and growth factors. Thus, STAT-3 can participate in the induction of inflammatory responses during coronavirus infections. STAT-3 can also suppress anti-virus interferon response and induce unbalanced anti-virus adaptive immune response, through influencing Th17-, Th1-, Treg-, and B cell-mediated functions. Furthermore, STAT-3 can contribute to the M2 macrophage polarization, lung fibrosis and thrombosis. Moreover, STAT-3 may be directly targeted by some virus-derived protein and operate as a pro-viral or anti-viral element in a virus-specific process. Here, the possible contribution of STAT-3 to the pathogenesis of COVID-19 was explained, while providing potential approaches to target this transcription factor in an attempt for COVID-19 treatment. •STAT-3 can be activated by numerous cytokines during COVID-19.•STAT-3 is hyper-activated and can play a central role in COVID-19 pathogenesis.•Activated STAT-3 can promote hyper-inflammation, lung fibrosis and thrombosis.•Activated STAT-3 promotes lymphopenia and impairs anti-virus immune responses.•STAT3 may be a potential therapeutic target for the treatment of COVID-19.