Table 1.

COVID-19 Disease Progression: Pathophysiology and Immune Response.

Disease progression	Local pathophysiology	Stage wise immune response
Stage 1 Asymptomatic stage	Entry of virus in nasal passage Epithelial cells (particularly Ciliated cells) get affected [14]. ACE2 is important receptor along with TMPRSS2 [15,16]. Although less viral load, individuals are infectious.	Mild Innate immune response. Th1 response by host is crucial to decide fate of infection.
Stage 2 Upper Respiratory Tract involvement	Sputum swab exhibit SARS CoV-2 In few Cough, sore throat starts here. In most cases progression ends here.	Strong Innate immune response. Increased plasma IP-10,MIG, IL- 8 and MCP levels during the first week are considered independent predictor of outcome & with adverse outcome. (intensive care unit admission or death) [17,18]
Stage 3 Lower Respiratory Tract involvement	Virus starts affecting alveoli. It affects type II pneumocytes (responsible for production of surfactant and are precursor for type I pneumocytes) than type I pneumocytes (responsible for gaseous exchange). Type II pneumocytes undergo apoptosis and die due to viral particles [19].	Aggravated immune response: Cytokine storm: lower lymphocyte counts and higher plasma concentrations of a number of inflammatory cytokines such as IL- 6 and tumor necrosis factor (TNF) [20].
	DAD: Diffuse alveolar lung damage: This is most commonly seen histopathologic feature [21]. Histologically: Injury to the alveolar epithelial cells, Hyaline membrane formation, Hyperplasia of type II pneumocytes, Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters [22].	Crucial role of T cells: Another study reported that CD4+ T cells, CD8+ T cells, and natural killer cells were reduced in severely ill patients compared with those with mild disease symptoms. Moreover, a substantial reduction of CD4+ T cell and CD8+ T cell counts in the peripheral blood was also observed in a patient who died [23].
	Alveolar macrophages affected: Alveolar macrophages expressing ACE2 are again target cells for SARS-CoV-2 infection.
	Alveolar condensation, Ground glass infiltrations, Hypoxia
Stage 4 ARDS, MODS	Acute Respiratory Distress SyndromePulmonary thrombosis HLH-like (haemophagocytic lymphohistiocytosis) cytokine storm with characteristics of HLH, including hypercytokinemia, unremitting fever, cytopenias, hyperferritinemia, and multi- organ damage, are commonly seen in seriously ill patients with COVID-19 [20].	Raised Serum Ferritin (doubling in24 h) and raised IL-6, LDH, D- dimer, C-reactive Protein (CRP) levels mark severe condition.