Recent evidence has suggested that the binding of TLR4 to the SARS-CoV-2 spike protein could serve as an alternative gateway into human cells, ultimately, aggravating the hyperinflammatory response characterized by increased TNF-α, interleukin (IL)-1, IL-2, IL-6, IL-7, IL-18, interferon-gamma, granulocyte-macrophages colony-stimulating factor, and monocyte chemoattractant protein-levels, known as a cytokine storm, a hallmark feature of COVID-19 (Fig. 1) [62]. Here, TLR4 is linked to COVID-19.