Theoretical data from previous coronavirus outbreaks has suggested a strong role for type I interferon, B-cells released antibodies, tumor necrosis factor-, and other cytokines in the viral immune response (Fig 1).2-4 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-17eproducing T cells. Tumor necrosis factor- promotes dendritic cell differentiation, leukocyte recruitment, and mediates fever. 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.
Broad immunosuppression across multiple cytokine axes with immunosuppressants has the potential to increase susceptibility, persistence, and reactivation of viral infections. Immunosuppressants decrease cytokines that recruit and differentiate immune cells needed to clear the infection. In addition, inflammatory mediators can become hyperactivated, resulting in a ‘‘cytokine storm,’’ which is the primary cause of death in severe disease.
Whether withdrawal of broadly immunosuppressive therapies may increase the risk of precipitating cytokine storm is unknown. Therefore, classic immunosuppressants may present the most concerning risk for those affected by COVID-19 (Table I). Immunomodulators, such as biologics, that do not target vital domains within the viral immuneresponse may dampen, but not significantly affect viral clearance.
Currently, there are no data describing the benefits or risks of stopping immunomodulators/ immunosuppressants during the COVID-19 outbreak. However, each medication’s mechanism of action, administration method/frequency, and pharmacokinetics/pharmacodynamics are important to consider. Nonbiologic medications, including small molecule inhibitors and immunosuppressants, are typically easier to stop and restart within days to weeks due to shorter half-life. Meanwhile, biologics generally have a longer half-life and include a risk of antidrug antibody formation with treatment cessation and subsequent continuation. However, biologics also tend to be more targeted and less involved in the previously mentioned components of the viral immune response. General medication considerations are included in Table I. Although patient dependent, clinicians may consider weaning patients with stable disease off of immunosuppressants
Reference & source information : https://www.jaad.org/
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