Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities? |
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| Institution: | 1. Department of Medicine, Cardiology and Nuclear Imaging Division, Clinical Hospital, Federal University of Pernambuco, Recife, Pernambuco, Brazil;2. Recife Medical School, Federal University of Pernambuco, Recife, Pernambuco, Brazil;3. Department of Medicine, Angiology Division, Federal University of Pernambuco, Recife, Pernambuco, Brazil;4. Department of Surgery, Experimental Surgery Unit, Federal University of Pernambuco, Recife, Pernambuco, Brazil;5. Department of Medicine, Allergy and Clinical Immunology Division, Clinical Hospital, Federal University of Pernambuco, Recife, Pernambuco, Brazil;6. Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA;7. Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA |
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| 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 patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression 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. We hypothesize 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, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure. |
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| Keywords: | SARS-CoV-2 Toll-like receptors-4 COVID-19 Cardio metabolic diseases Obesity Diabetes Hypertension Atherosclerosis |
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