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

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.

Keywords: COVID-19; atherosclerosis; endothelium; immunity; thrombosis.

Figure 1. Activities of angiotensin (1-7), subproduct of angiotensin 1, and consequences of blocking. Angiotensin-converting enzyme 1 (ACE1) and angiotensin-converting enzyme 2 (ACE2) act on angiotensins 1 and 2. The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) S protein binds to the ACE2 receptor of the human cell, reducing its enzyme activity. AT1R = type 1 angiotensin II receptor; AT2R = type 2 angiotensin II receptor; MASR = angiotensin 1-7 MAS receptor.

Figure 2. Strategies for treatment of COVID-19 according to clinical disease phase. *Studies in progress; ^†Dose adjustment by weight and creatinine clearance (ClCr); ^‡ECMO (extracorporeal membrane circulation); ^§When there is a strong clinical suspicion of venous thromboembolism or confirmation of pulmonary embolism or proximal deep venous thrombosis (adjustment to weight and CrCl).

Figura 1. Ações da angiotensina 1-7, subproduto da angiotensina I, e consequências do seu bloqueio. A enzima conversora de angiotensina 1 (ECA1) e a enzima conversora de angiotensina 2 (ECA2) agem na angiotensina I e II. A proteína S do SARS-CoV-2 (coronavírus 2 da síndrome respiratória aguda grave) se liga ao receptor ECA2 da célula humana, reduzindo sua atividade enzimática. AT1R = receptor da angiotensina II tipo 1; AT2R1 = receptor da Angiotensina II tipo 2; MASR = receptor MAS da angiotensina 1-7.

Figura 2. Estratégias de tratamento da COVID-19 de acordo com a fase clínica da doença. *Estudos em andamento; ^†Ajuste da dose pelo peso e clearance de creatinina (ClCr); ^‡ECMO (circulação por membrana extracorpórea); ^§Quando forte suspeita clínica de tromboembolismo venosos ou confirmação de embolia pulmonar ou trombose venosa profunda proximal (ajuste ao peso e ClCr).