Post-transplant immunosuppression and COVID-19: From a double whammy to a mixed blessing

Figure 1 Chronology of events during the severe acute respiratory syndrome coronavirus 2 infection and targets for immunosuppressants and immunomodulators. A and B: Person-to-person transmission of the severe acute respiratory syndrome coronavirus 2 occurs through respiratory secretions of infected individuals; C: The virus infects cells which express surface receptors Angiotensin-converting enzyme 2 leading to intense pyroptosis and release of damage associated molecular patterns, which along with the viral components are recognised by epithelial cells and macrophages; D and E: These antigen presenting cells then trigger the generation of pro-inflammatory cytokines stimulating the immune cascade pathways, leading to a differentiation of T and B cells, followed by activation of B cells into plasma cells to produce viral neutralising antibodies; F: Usually these antibodies block viral infection, and alveolar macrophages recognize neutralized viruses and apoptotic cells and clear them by phagocytosis; and G: However, when unchecked the escalating cascade of the immune system with production of chemokines leads to a cytokine storm. (Inset) Intracellular targets of immunosuppressants and their role in suppressing the inflammatory/immune response. Inhibition: Red line; APC: Antigen presenting cell; CD: Cluster differentiation; MCP1: Monocyte chemoattractant protein 1; GCSF: Granulocyte colony stimulating factor; IL: Interleukin; FGF: Fibroblast growth factor; GMCSF: Granulocyte-macrophage colony stimulating factor; NF-κB: Nuclear factor κB; IP10: Interferon-induced protein 10; VEGFA: Vascular endothelial growth factor A; IRF: Interferon regulatory factor; PDE4: Phosphodiesterase 4; MIP1A: Macrophage inflammatory protein 1A; TNFα: Tumor necrosis factor α; NFAT: Nuclear factor of activated T cells; PDGF: Platelet-derived growth factor; PKA: Protein Kinase A; TH: T-helper cell.