Decreased production of antiviral factors in patients infected with SARS-CoV-2 due to reduced TLR7 expression

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic presents a major global health challenge. Innate immunity is a key defense against viral infections and influences disease progression. Similar to SARS-CoV-1, which can suppress interferon (IFN) production to evade the immune response, SARS-CoV-2 May also impair antiviral pathways. To investigate this, we analyzed the expression of interferon-stimulated genes (ISGs) in 48 SARS-CoV-2-infected patients using real-time polymerase chain reaction (RT-qPCR) and assessed toll-like receptor (TLR7) expression in blood cells via flow cytometry. Results showed that infected individuals had reduced baseline expression of antiviral factors and a diminished response to stimulation with a TLR7/8 agonist (CL097), compared to healthy individuals. A decrease in pattern recognition receptors (PRRs) was also observed at both the gene and protein levels. These findings support the hypothesis that SARS-CoV-2 disrupts the IFN signaling pathway, similar to SARS-CoV-1. Reduced expression of innate immune receptors appears to impair the production of antiviral molecules, potentially delaying viral clearance and worsening disease outcomes. This highlights the importance of innate immune regulation in SARS-CoV-2 infection and may help inform future therapeutic strategies. The virus that causes coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has a way of weakening the body’s early immune defense, called the innate immune system. This system is supposed to act fast, recognizing viruses and sending out signals to fight them before they spread too much. In people infected with SARS-CoV-2, scientists noticed that certain important genes – called interferon-stimulated genes – and sensors like toll-like receptor (TLR7), which help detect viruses, are less active than usual. These parts of the immune system don’t turn on properly, even when scientists try to trigger them using lab tools. This means the virus is interfering with the interferon signaling pathway, which is like the body’s alarm system for viral infections. If this alarm system doesn’t work, the immune response is delayed, and the virus can spread more easily in the body. That may lead to more severe illness in some people.