AUTHOR=Xue Junjian , Wang Xiaoyin , Wang Hui , Qiao Bin , Gao Pengfei , Ren Bin , Yan Shushan TITLE=Unraveled role of TLR7-mediated interferon signaling activation in COVID-19 JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1658249 DOI=10.3389/fcimb.2025.1658249 ISSN=2235-2988 ABSTRACT=Emerging evidence underscores the critical role of Toll-like receptor 7 (TLR7)-mediated interferon (IFN) signaling in host defense against viral infections including SARS-CoV-2, through the modulation of both innate and adaptive immunity. However, the specific mechanisms by which TLR7 activation shapes SARS-CoV-2-specific immune responses, particularly via IRF-IFN pathways, remain incompletely elucidated. This review synthesizes current findings on how intrinsic TLR7-driven IFN signaling influences viral clearance, modulates adaptive immunity, and contributes to autoantibody production in COVID-19. A deeper understanding of these processes is essential for developing targeted therapeutic interventions and improved vaccines aimed at mitigating severe COVID-19 and preventing post-acute sequelae of SARS-CoV-2 infection (PASC).