Having established that SARS-CoV-2 spike protein induces comparable ISG responses in THP-1 monocytes as the infectious virus and enhances chemokine ISG expression in response to hypoxia, we reached out to determine if TLR4 and cholesterol dynamics are also involved in interferon-associated immune responses in monocytic THP-1 cells upon infection with SARS-CoV-2 in a hypoxic environment. The gene discussed is TLR4; the disease is infection.