Introduction
Following reports of severe pneumonia cases of unknown etiology from Wuhan, China, multiple groups identified the pathogenic agent responsible for the current COVID-19 pandemic as the SARS-CoV-2 virus (Chan et al., 2020; Huang C. et al., 2020; Zhu et al., 2020). The last several months have seen an unprecedented surge in research efforts to understand the underlying molecular mechanisms associated with SARS-CoV-2 infectivity, immunogenicity, and pathogenesis. Since it is now evident that SARS-CoV-2 employs the same set of receptors and host cells, previously utilized by SARS-CoV, various disease models were developed to understand the molecular networks implicated in viral evasion, host immune response, and immuno-pathogenesis. Multiple factors and pathways are already known based on previous knowledge from other coronaviruses, which have shown promising potential as therapeutic targets (Tay et al., 2020). But a more comprehensive understanding to develop highly effective therapies is yet to emerge, which demands better molecular details at various stages of the virus propagation and disease progression in the host cells. In the initial early mild phase of infection (Stage I), the virus remains confined to the upper respiratory tract (nasal cells, some areas of pharynx and larynx) which elicits low levels of the innate immune response (if any). This asymptomatic state lasts for a couple of days (generally one or two days) before the virus propagates to the conducting and terminal airways (Stage II). During this stage of the disease, an optimal but controlled adaptive and innate immune response will help to combat the infection. Successful viral clearance from recovered patients, show the presence of adequate adaptive immune cells along with the immunomodulatory molecules and neutralizing antibodies (Cao, 2020; Tay et al., 2020). However, an impaired adaptive immune response at this stage, with concomitant overactivation of the innate immune system (inflammatory macrophages and neutrophils) can lead to severe disease symptoms in ∼20% of COVID-19 patients (Wu and McGoogan, 2020). Recent clinical and histopathological data from deceased patients suggest adaptive immune dysfunction and heightened proinflammatory response with inflammatory cell infiltration into the lungs (Stage III). Further, the disease severity positively correlated with increased levels of proinflammatory IL-6 and an increase in the neutrophil/lymphocyte ratio (Liu T. et al., 2020; Tan L. et al., 2020b; Tan M. et al., 2020c). Between 3 and 17% of COVID-19 patients developed acute respiratory distress syndrome (ARDS), as a result of hyper inflammation (excessive infiltration of activated innate immune cells and cytokine release syndrome) and lymphocytopenia (reduced levels of CD4+, CD8+, and B cells) (Gibson et al., 2020). These changes are followed by cell death and tissue destruction, which ultimately leads to airway collapse, multiple organ failure and death in 67–85% of ICU patients, based on the available data so far (Wu and McGoogan, 2020; Xu Z. et al., 2020; Zhang H. et al., 2020). Here, we discuss the molecular determinants implicated in the success or failure of recovery through various phases of immune response generated by the host cells. We have built an immunological trajectory of COVID-19 patients who have successfully cleared the virus against those who have developed severe symptoms, with emphasis on virus sensing and evasion mechanisms, and the spatiotemporal role of the innate and adaptive immune system. Further, we provided cellular and molecular details of cytokine storm and ARDS in COVID-19 patients.