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

Simone Cristina Soares Brandão; Júlia de Oliveira Xavier Ramos; Luca Terracini Dompieri; Emmanuelle Tenório Albuquerque Madruga Godoi; José Luiz Figueiredo; Emanuel Sávio Cavalcanti Sarinho; Sarvesh Chelvanambi; Masanori Aikawa

doi:10.1016/j.cytogfr.2020.09.002

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

Cytokine Growth Factor Rev. 2021 Apr:58:102-110. doi: 10.1016/j.cytogfr.2020.09.002. Epub 2020 Sep 21.

Authors

Simone Cristina Soares Brandão¹, Júlia de Oliveira Xavier Ramos², Luca Terracini Dompieri², Emmanuelle Tenório Albuquerque Madruga Godoi³, José Luiz Figueiredo⁴, Emanuel Sávio Cavalcanti Sarinho⁵, Sarvesh Chelvanambi⁶, Masanori Aikawa⁷

Affiliations

¹ Department of Medicine, Cardiology and Nuclear Imaging Division, Clinical Hospital, Federal University of Pernambuco, Recife, Pernambuco, Brazil. Electronic address: sbrandaonuclearufpe@gmail.com.
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 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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.

Keywords: Atherosclerosis; COVID-19; Cardio metabolic diseases; Diabetes; Hypertension; Obesity; SARS-CoV-2; Toll-like receptors-4.

Publication types

Review

MeSH terms

COVID-19 / complications*
COVID-19 / epidemiology
COVID-19 / pathology
Cardiometabolic Risk Factors
Cardiovascular Diseases / epidemiology
Cardiovascular Diseases / etiology*
Comorbidity
Cytokine Release Syndrome / epidemiology
Cytokine Release Syndrome / etiology
Humans
Metabolic Diseases / epidemiology
Metabolic Diseases / etiology*
Multiple Organ Failure / epidemiology
Multiple Organ Failure / etiology
SARS-CoV-2 / pathogenicity*
Severity of Illness Index
Toll-Like Receptor 4 / physiology*

Substances

TLR4 protein, human
Toll-Like Receptor 4