**2. Pathogenesis of COVID-19**

The recently identified SARS-CoV-2 is a new member added into the family of β-coronavirus with earlier known members like Severe Acute Respiratory Syndrome

#### *The Role of Complementary and Alternative Medicines in the Treatment and Management... DOI: http://dx.doi.org/10.5772/intechopen.100422*

Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which results in severe pulmonary pneumonia and potentially deadly acute respiratory distress syndrome (ARDS). The large population of COVID-19 patients is asymptomatic. Six prominent symptoms include dry cough, malaise, fatigue, fever, dyspnea, secretion or sputum among various clinical manifestations noticed in patients infected with SARS-CoV-2. The gastrointestinal symptoms consist of vomiting, anorexia, and diarrhea in the patients affected with COVID-19. Pathogenesis of COVID-19 is classified into three discrete clinical phases based on the cells/tissue being infected. These three phases include asymptomatic state, upper and conducting airway response and hypoxia, ground-glass infiltrates and progression to ARDS. In Phase, I of asymptomatic state inhaled SARS-CoV-2, bind to the receptor present on the epithelial cells i.e., angiotensin-converting enzyme-2 (ACE-2) on the nasal cavity and begin reproducing [18]. There is local propagation of the COVID-19 virus and an inadequate innate immunity in the asymptomatic stage. In phase II, there is an occurrence of the upper airway and conducting airway infection. In this phase or stage, there is a robust immune response when the virus migrates and propagates down the conducting duct and along the respiratory tract. Epithelium of the upper and conducting airway infected virally results in the release of cytokines [19]. During this phase, clinical manifestations are observed. Predictions and monitoring of the subsequent course of the disease may be improved by determining the host immune responses. In most of the patients infected with SARS-CoV-2, the infection will be mild and mostly limited to the upper and conducting airways [20]. These patients do not require hospitalization and may be monitoring of patients at home with conventional symptomatic treatment will be adequate [19]. In the third stage or phase III, there will be ground-glass infiltrates, hypoxia and progression to ARDS. Typically, around 20% of the patients infected with SARS-CoV-2 advance to the severe stage and develop pulmonary infiltrates and ARDS. In this stage, the virus reaches and infects the gas exchange unit of the lungs i.e., alveolar type II cells mainly in the subpleural region of lungs [21]. Once the virus reaches the type II alveolar cells self-replicating pulmonary toxins are released and it results in apoptosis and cell death [22]. This in turn causes diffuse alveolar injury, with a few multinucleated large cells and a fibrin membrane rich in hyaline [23, 24]. Extensive scarring, fibrosis, and various kinds of ARDS may occur from aberrant wound healing. Improvement requires epithelial cells regeneration and robust innate and adaptive immune responses. Patients with older age or co-morbidities are at greater risk due to weakened capacity to repair the damaged epithelium and deteriorated immune response against the virus. In the elderly, the mucociliary clearance is also reduced and this allows propagation and rapid spread into the gas exchange unit of the lungs [25].
