COVID-19 and obesity: the meeting of two pandemics

ABSTRACT COVID-19 and obesity are two pandemic diseases that the world is currently facing. Both activate the immune system and mediate inflammation. A sequence of disease phases in patients with severe COVID-19 results in a cytokine storm, which amplifies the subclinical inflammation that already exists in patients with obesity. Pro-inflammatory cytokines and chemotactic factors increase insulin resistance in obesity. Therefore, a greater systemic inflammatory response is establishe, along with an increased risk of thrombotic phenomena and hyperglycemic conditions. These changes further impair pulmonary, cardiac, hepatic, and renal functions, in addition to hindering glycemic control in people with diabetes and pre-diabetes. This review explains the pathophysiological mechanisms of these two pandemic diseases, provides a deeper understanding of this harmful interaction and lists possible therapeutic strategies for this risk group.

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

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.

Mapping COVID-19 functional sequelae: the perspective of nuclear medicine.

Severe acute respiratory syndrome coronavirus 2 infection is capable of affecting several organs. Direct viral toxicity, pro-inflammatory and pro-thrombotic induction, endothelial damage, immune imbalance, and dysregulation of the renin-angiotensin-aldosterone system are the mechanisms underlying the viral potential of multiple organ damage. The impairment of four organs stands out among severe patients: lung, heart, kidney, and endothelium. The nuclear medicine field holds accurate and safe exam techniques, such as positron emission tomography-computed tomography and scintigraphy, that allow the anatomophysiological study of the majority of human organ systems. By choosing the most appropriate method and radiopharmaceutical, analyzing the presence of inflammation, fibrosis, changes in perfusion, and function of desired organs is possible. Therefore, its use in the monitoring of patients with coronavirus disease 2019 becomes relevant, especially for monitoring sequelae. In this review, we discuss the use of Nuclear Medicine in the detection, monitoring, and therapeutic evaluation of pulmonary and extrapulmonary sequelae by coronavirus disease 2019.

Severe COVID-19: understanding the role of immunity, endothelium, and coagulation in clinical practice.

SARS-CoV-2 is responsible for the COVID-19 pandemic. The immune system is a determinant factor in defense against viral infections. Thus, when it acts in a balanced and effective manner the disease is self-limited and benign. Nevertheless, in a significant proportion of the population, the immune response is exaggerated. When infected, patients with diabetes, hypertension, obesity, and cardiovascular disease are more likely to progress to severe forms. These diseases are related to chronic inflammation and endothelial dysfunction. Toll-like receptors are expressed on immune cells and play an important role in the physiopathology of cardiovascular and metabolic diseases. When activated, they can induce release of inflammatory cytokines. Hypercoagulability, hyperinflammation, platelet hyperresponsiveness, and endothelial dysfunction occur in immune system hyperactivity caused by viral activity, thereby increasing the risk of arterial and venous thrombosis. We discuss the interactions between COVID-19, immunity, the endothelium, and coagulation, as well as why cardiometabolic diseases have a negative impact on COVID-19 prognosis.

COVID-19 grave: entenda o papel da imunidade, do endotélio e da coagulação na prática clínica / Severe COVID-19: understanding the role of immunity, endothelium, and coagulation in clinical practice

Resumo O SARS-CoV-2 é o responsável pela pandemia da COVID-19. O sistema imunológico é fator determinante no combate à infecção viral e, quando atua equilibrada e eficientemente, a doença é autolimitada e benigna. Uma parcela significativa da população, porém, apresenta resposta imune exacerbada. Os indivíduos diabéticos, hipertensos, obesos e com doenças cardiovasculares, infectados pelo vírus, apresentam maior chance de progredir para formas graves. Essas doenças estão relacionadas a processos inflamatórios crônicos e disfunção endotelial. Os receptores do tipo Toll estão presentes nas células de defesa e participam da imunopatologia de doenças cardiovasculares e metabólicas, levando à produção de citocinas pró-inflamatórias quando ativados. Devido à ação viral e à hiperativação do sistema imune, estados de hiperinflamação, hiperativação plaquetária, disfunção endotelial e hipercoagulabilidade são desenvolvidos, predispondo a tromboses venosas e arteriais. Discutiremos sobre a interação entre a COVID-19, a imunidade, o endotélio e a coagulação, como também sobre as possíveis causas de doenças cardiometabólicas impactarem negativamente na evolução da COVID-19.

Abstract SARS-CoV-2 is responsible for the COVID-19 pandemic. The immune system is a determinant factor in defense against viral infections. Thus, when it acts in a balanced and effective manner the disease is self-limited and benign. Nevertheless, in a significant proportion of the population, the immune response is exaggerated. When infected, patients with diabetes, hypertension, obesity, and cardiovascular disease are more likely to progress to severe forms. These diseases are related to chronic inflammation and endothelial dysfunction. Toll-like receptors are expressed on immune cells and play an important role in the physiopathology of cardiovascular and metabolic diseases. When activated, they can induce release of inflammatory cytokines. Hypercoagulability, hyperinflammation, platelet hyperresponsiveness, and endothelial dysfunction occur in immune system hyperactivity caused by viral activity, thereby increasing the risk of arterial and venous thrombosis. We discuss the interactions between COVID-19, immunity, the endothelium, and coagulation, as well as why cardiometabolic diseases have a negative impact on COVID-19 prognosis.