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