Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID-19 cases have been reported in 185 countries. Some patients with COVID-19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS-CoV-2 infection as well as immunotherapeutic strategies for COVID-19. Immune evasion by SARS-CoV-2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS-CoV-2 infection. Some potential immunotherapeutic strategies to control the progression of COVID-19, such as passive antibody therapy and use of interferon αβ and IL-6 receptor (IL-6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID-19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.

Keywords: COVID-19; SARS-CoV-2; coronavirus; immune response; immunotherapeutic.

FIGURE 1

Immune responses and immunotherapy strategy in SARS‐CoV‐2 infection. Immune response to SARS‐CoV‐2 involving innate and adaptive immunity. A1, SARS‐CoV‐2 enters the host cells by binding the receptor for angiotensin converting enzyme 2 (ACE2). The infected cells then release interferon type I (IFN‐α/β); innate immune cells respond to the IFNs by establishing an antiviral state. In case of severe infection, the viruses are sensed by monocytes, tissue macrophages, and resident dendritic cells resulting in uncontrolled proinflammatory cytokine (IFN, TNF‐α, IL‐1β, and IL‐6) production, leading to a phenomenon called the cytokine storm, which damages the host’s respiratory epithelial cells. Exhausted natural killer cells with increased expression of the inhibitory receptor, NKG2A, are also seen in SARS‐CoV‐2. A2, In SARS‐CoV‐2 infection, increased antibody production and poor T cell responses are observed (A2). CD4+ T cell and CD8+ T cell numbers decrease, and the exhausted phenotype, which is characterized by a higher expression of inhibitory receptors, such programmed death receptor‐1 (PD‐1) and cytotoxic T lymphocyte associated antigen‐4 (CTLA‐4), is seen. Immunotherapy strategies for SARS‐CoV‐2 have been proposed. B1, Transferring convalescent sera with neutralizing antibodies from the recovered patients. The antibodies can directly bind to SARS‐CoV‐2 and prevent the virus from infecting new cells (neutralization), enhance phagocytosis (opsonization), recruit complement to lyse infected cells or neutralize the viruses, and promote NK cell mediated killing of infected cells through antibody dependent cellular cytotoxicity (ADCC). B2, IFN α/β bind to IFN receptors and induce an antiviral response by expressing several interferon stimulated genes (ISGs), such as PKR, OAS, and Mx. The protein product of ISGs controls viral infection. (B3) The IL‐6R inhibitor (such as tocilizumab) binds to the membrane bound IL‐6 receptor (mIL‐6R) and soluble IL‐6 receptor (soluble IL‐6R). Binding of tocilizumab to IL‐6R inhibits the IL‐6 signaling pathway