Understanding the immunopathogenesis of COVID-19: Its implication for therapeutic strategy

Abstract

Although 80% of individuals infected with the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) recover without antiviral treatments, the other 20% progress to severe forms of pulmonary disease, suggesting that the host’s immune response to the virus could influence the outcome of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects alveolar epithelial type 2 cells expressing angiotensin-converting enzyme 2, and these infected epithelial cells recruit dendritic cells, neutrophils and monocytes /macrophages, leading to the activation of CD4+ and CD8+ T cells. These cells launch an antiviral immune response, but are able to completely suppress viral replication or completely eradicate virus in a limited proportion of infected patients. In other patients, viral suppression is incomplete and the numbers of circulating B and T cells are subsequently reduced by as yet unknown mechanisms. Some patients with sustained viral replication progress to a severe condition called cytokine storm. Although antiviral drug(s) should be considered early in infection to prevent progression, there have been no antiviral therapies proven to be effective for significantly inhibiting the viral replication in vivo and suppressing the progression to cytokine storm. Blocking the action of cytokines with dexamethasone or anti-interleukin-6 could have a pivotal role in treatment of those patients. Therapeutic strategy should therefore be based on viral kinetics and the immunopathology of COVID-19.

Keywords: COVID-19, SARS-CoV-2, Immune response, Antibody, Viral kinetics, Treatment

Core Tip: Since the coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the core therapeutic strategy should be aimed at the eradication of the virus. Unfortunately, there have been no antiviral drugs proven to be effective for this viral infection. The pathogenesis of SARS-CoV-2 is formed by the interaction between the viral infection and the immune response to the virus, and the various clinical features observed in patients with COVID-19 could be due to differences in host immune responses. Moreover, therapeutic strategies should be based on both viral kinetics and the immune response. This editorial summarizes current understanding about immune responses in patients infected with SARS-CoV-2 and provides clues to therapeutic strategies based on this information.