The immune system view of the coronavirus SARS-CoV-2

Abstract

Knowing the "point of view" of the immune system is essential to understand the characteristic of a pandemic, such as that generated by the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2, responsible for the Coronavirus Disease (COVID)-19. In this review, we will discuss the general host/pathogen interactions dictating protective immune response or immunopathology, addressing the role of immunity or immunopathology in influencing the clinical infection outcome, and debate the potential immunoprophylactic and immunotherapy strategies required to fight the virus infection.

Keywords: COVID-19; Coronavirus; Monoclonal antibodies; SARS-CoV-2; Vaccine.

Fig. 1

Efficient anti-viral immunity phase as feature of mild infection. Mild infection is characterized by efficient anti-viral immunity phase aimed to eliminate viruses from the host and resolve the infection. A cytokine storm, prevalently formed by anti-viral cytokines (e.g., type-I [IFN-α] and type-III [IFN-λ]) and pro-inflammatory cytokines (IL-6, TNF-α, IL-1-β, etc), is produced by innate immune cells, such as macrophages and DCs. Various innate immune cells (ILCs, NK cells, NKT cells) also intervene to limit viral spread. Consequently, the adaptive responses are mounted to both directly kill virus-infected cells by antigen-specific effector CD8⁺ T cells and to neutralize the virions by antibody producing antigen-specific B cells. IFN-γ production by T cells, as well as by ILCs, NK and NKT cells contribute to viral clearance. Finally, memory T and B cells are generated to guarantee the host protection against secondary infections. An immunoregulatory mechanism mediated by immune checkpoint blockade (e.g., by PD-1, CTLA-4) and Tregs results crucial for the resolution of immunopathology

Fig. 2

Inefficient anti-viral immunity as feature of severe infection. Severe infection is characterized by inefficient anti-viral immunity and increased immunopathology addressed to provide inflammation (by IL-6, TNF-α, IL-1-β, etc) rather than protection (by IFN-α, IFN-λ, IFN-γ). Effector T cells and likely ILCs and NK cells, which are stimulated by the persisting virus, undergo consecutive steps of exhaustion (partially and then fully exhaustion) and, together with the parallel expansion of Tregs and suppressive cytokines (e.g., IL-10, TGF-β), establish a state of prolonged inflammation. In addition, the hypothesis that BIA is sustained by the expansion of autoreactive CD8⁺ T cells specific to apoptotic epitopes (AEs), which are induced by the cross-presentation of activated apoptotic T cells by DCs, is also considered. Under these conditions, the inefficient anti-viral immunity response does not result in the development of immunological memory. This immune dysregulation leads to severe clinical sequelae (often requiring intensive care units) that undergo restoration in the majority of patients, and death in some of them. The therapeutic approaches will be addressed, firstly, to limit or clear the viral load by various, non-mutually exclusive antiviral strategies (antiviral drugs, plasmatherapy, mAbs neutralizing the virus) in both scenarios displayed in Figs. 1 and 2, to which can be associated various immunotherapy-based biologicals (e.g., anti-IL-6R, anti-IL-1, anti-TNF mAbs), as well as anticoagulants, in an attempt to put out the cytokine storm in the severe form of infection