Here, we review the roles of TLRs in the pathogenesis of COVID-19, including TLR7 and TLR3 rare variants, as well as the L412F polymorphism in TLR3 that negatively regulates anti-SARS-CoV-2 immune responses, the interaction of TLR2 and TLR4 with SARS-CoV-2 proteins, TLR3-related cellular senescence and the implication of TLR2 in NET formation by SARS-CoV-2 (Figure 3). This evidence concerns the gene TLR4 and COVID-19.