Clinical presentation, pathophysiology and histopathology

The Coronavirus Pandemic and the Future: Virology, Epidemiology, Translational Toxicology and Therapeutics

Source: © Royal Society of Chemistry

An overview of tranmission, symptoms, clinical trajectory and disease spectrum of COVID-19

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This chapter describes the various modes of viral transmission, the signs and symptoms, and the distinct clinical trajectory and disease spectrum of COVID-19. It also describes the mechanism of SARS-Cov-2 invasion into host cells and the various disease manifestations of COVID-19. Direct transmission of the virus is from person to person through respiratory droplets or aerosols and physical contact while indirect transmission is through contaminated surfaces. As a respiratory virus, SARS-CoV-2 must gain entry to cells lining the respiratory tract. Entry is gained by the binding of the virus spike to the peptidase angiotensin converting enzyme 2 (ACE2) metalloprotease and the virus is internalised where ACE2 receptors are plentiful and TMPRSS2 (transmembrane serine protease) expression is highest. This occurs in ciliated nasal epithelial cells and also in ciliated bronchial epithelial cells and surfactant-producing type II alveolar epithelial cells. Incapacitation of these cells serves to enhance the pathogenicity of the virus which then infects other cells, multiplies, and colonises target organs in various parts of the body that offer ACE2 receptors. It is not clear why a substantial proportion of SARS-CoV-2–infected individuals report few, if any, symptoms and recover completely, while chest computed tomography (CT) provides evidence that viral pneumonitis is present in >90% of symptomatic cases within 3 to 5 days of onset. Indeed, infection that occurs via asymptomatic or pre-symptomatic cases presents a severe challenge for preventing viral transmission. 

Commonly observed symptoms of COVID-19 are tiredness, headache, fever and dry cough. Patients also present with non-respiratory symptoms that include gastrointestinal disorders, olfactory dysfunction (impairment or loss of smell), loss of taste, neurological problems and cardiovascular effects. The symptoms of COVID-19 range from totally asymptomatic to severe and life-threatening conditions characterised by pulmonary dysfunction that requires mechanical ventilation and intensive care. In patients with pre-existing conditions such as immune compromise, hypertension and cardiovascular disease, obesity and diabetes, symptoms may quickly progress to multi-organ conditions including multi-organ failure, sepsis, and septic shock. Overall, clinical features have been described based on the increasing severity of the symptoms as asymptomatic /pre-symptomatic, mild, moderate, severe and critical. The progression from mild to moderate symptoms usually occurs between 7 and 14 days consistent with the recommended quarantine period following suspected exposure to the virus. Ensuing inflammatory responses occur with cytokine release as the disease progresses from mild to severe stages. Acute Respiratory Disease Syndrome (ARDS), cardiac sequelae, structural and functional disturbances in liver and kidney are manifestations associated with the severe disease. Pathogenesis, with special emphasis on immunopathology, and clinical features are dealt with in this chapter and may present us with possible drug targets and vaccine epitopes. Finally, the various morbidities resulting from the disease are discussed in detail.