Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Abstract The severe form of COVID-19 is marked by an abnormal and exacerbated immunological host response favoring to a poor outcome in a significant number of o patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the over expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. The SARS-CoV-2 initially infects cells in the upper respiratory tract and, in some patients, spread very quickly, needing respiratory support and systemically, causing collateral damage in tissues. Our hypothesis is that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host's lungs, accumulating secretions and hindering blood oxygenation and the cytokine storm, along with the immune system attacks the body, leading to multiple organ failure.