Theoretical data from previous coronavirus outbreaks has suggested a strong role for type I interferon, B-cell–released antibodies, tumor necrosis factor-α, and other cytokines in the viral immune response (Fig 1 ).2, 3, 4 Interleukin (IL) 17 cytokines are important for immune cell recruitment to infection sites to promote clearance, while also activating downstream cascades of cytokines and chemokines.4 IL-1 promotes fever and the differentiation of T-helper cells to IL-17–producing T cells. Tumor necrosis factor-α promotes dendritic cell differentiation, leukocyte recruitment, and mediates fever.4 Antibodies produced by plasma cells help to neutralize the virus, limit infection, and prevent future infections. Disruption of B-cell differentiation into plasma cells could limit antibody production.3
Fig 1 COVID-19 viral immune response and targets of common dermatologic immunomodulators and immunosuppressants. (Left) (1) Person-to-person transmission of COVID-19 occurs though direct contact with respiratory secretions of infected individuals.2 The virus invades host cells by binding to their receptors and fusing with the cell membrane. (2) It is hypothesized that once inside the body, the lung epithelial cells become the primary target, where the receptor binding domain of the virus spikes bind to angiotensin-converting enzyme 2 (ACE2) receptors of ACE2-expressing target cells. (3) Although not confirmed, it is believed the virus dampens the initial type 1 interferon (IFN) responses, which contributes to uncontrolled viral replication. (4) Once the virus is identified, macrophages present viral components to activate and induce (5) differentiation of T cells and B cells. (6) Activated B cells differentiate into plasma cells that produce antibodies important for neutralizing viruses. (7) The resulting inflammatory cytokines and antibodies continue to stimulate the production of additional cytokines and antibodies, which may contribute to the “cytokine storm” noted in those with severe disease. (8) The inflammatory cytokines and antibodies also promote the influx of neutrophils, monocytes, and macrophages along with additional inflammatory cytokines. (Right) The drug targets for common dermatologic immunomodulators and immunosuppressants have also been included in this diagram. FGF, Basic fibroblast growth factor; GCSF, granulocyte-colony stimulating factor; GMCSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; IP10, interferon γ-induced protein 10; IRF, interferon regulatory factor; MCP1, monocyte chemoattractant protein 1; MIP1A, macrophage inflammatory protein 1-α; NFAT, nuclear factor of activated T cells; NF-κB, nuclear factor-κB; PDE4, phosphodiesterase 4; PDGF, platelet-derived growth factor; PKA, protein kinase A; TH, T-helper cell; TNF, tumor necrosis factor; VEGFA, vascular endothelial growth factor A. Created with Biorender.com.