COVID-19 Pathophysiology, Clinical Manifestations, and Drug Treatment

Abstract

COVID-19 is caused by a single-stranded RNA encapsulated betacoronavirus, known as SARS-CoV-2, implicated in the pandemic that started in China in 2019. Viral replication consists of five stages that culminate in the release of the new virion. The exaggerated inflammatory response of COVID-19 is characterized by an elevation of acute phase reactants such as C-reactive protein and ferritin. It is associated with an unfavorable clinical course, intensified by abnormal activation of the protein complex called the inflammasome. When the immune response does not control the virus, lung tissue damage occurs that leads to the massive release of proinflammatory cytokines, producing acute respiratory failure syndrome. Vascular permeability is increased; interaction with coagulation factors develops disseminated intravascular coagulation and multiorgan failure. Up to 33% of cases can be asymptomatic. Clinical manifestations can be mild or severe and involve various organs and systems. Among the most commonly affected are: respiratory, cardiovascular, renal, and hematological and coagulation systems. Among the most representative laboratory data are: elevation of inflammatory markers (CRP, inflammatory cytokines, tumor necrosis factor), high levels of D-Dimer, elevation of troponin I, lymphopenia, thrombocytopenia, alteration of liver enzymes and kidney function. There are risk factors and comorbidities that contribute to the severity of the clinical picture (mainly cardiovascular and metabolic diseases): diabetes mellitus, high blood pressure, obesity, chronic lung diseases, cancer, and chronic kidney failure. There are also other genetic factors associated with the host’s immunopathogenesis and response to SARS COV-2 infection. There are various imaging methods that allow adequate identification and involvement of the pulmonary and cardiovascular systems with great sensitivity and specificity (computed tomography and echocardiography). The pandemic imposed decisions with very little information regarding what may be useful as a therapeutic strategy. This uncertainty applies to the treatment indicated in the prevention phase, as well as to the different stages of severity of the disease. In many cases, treatments were applied without having gone through a trial phase but only with the theoretical support of its probable benefit. However, over time, controlled studies showed that they did not provide any benefit and that they could even have a deleterious effect. Other therapies still in use have shown contradictory results in the different clinical trials where they were tested. Very few therapeutic options have shown undisputable benefit so far. The only ones that can modify the presentation or course of the disease are vaccines, which have also been developed in record time and in controlled trials, and all those that have been approved showed a decrease in the risk of infection and in the risk of presenting a severe manifestation of the disease.<br>