Therapy with Cyclosporine in the Context of the Coronavirus Pandemic
The rapid spread of the SARS-CoV-2 virus and the associated COVID-19 disease pandemic raises concerns about possible risks associated with immunosuppressive treatment of autoimmune diseases. Specifically, does the use of cyclosporine increase the risk of infection, or does it act protectively?
Mechanism of Action and Indications of Cyclosporine A
Cyclosporine A is one of the most commonly used immunosuppressants. It acts selectively against T lymphocytes and belongs to the group of calcineurin inhibitors by its mechanism of action.
It has found broad use in dermatology (in the treatment of atopic dermatitis and psoriasis), rheumatology (in the therapy of rheumatoid arthritis), nephrology (in the diagnosis of nephrotic syndrome), ophthalmology (in patients with endogenous uveitis), and transplant medicine.
Does the use of cyclosporine increase the risk of viral infections?
Some publications mention severe infections in patients using cyclosporine. Nevertheless, the risk of common infections is relatively low and comparable to placebo. In a study that included a total of 225 patients receiving cyclosporine for 12 months, none of them showed reactivation or new infection caused by varicella zoster virus, herpes simplex virus 1/2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or HIV. Thus, a hypothesis followed that cyclosporine might act therapeutically in patients with certain viral infections.
Numerous in vitro results suggest broad-spectrum antiviral effects of cyclosporine. Specifically, this immunosuppressant inhibits the replication of hepatitis B and C viruses, HIV, influenza virus, West Nile fever, Rift Valley fever, and Zika virus by blocking the interaction of cellular receptors (cyclophilins) with viral proteins and inhibiting viral RNA synthesis.
Efficacy Against Coronaviruses
Studies on cyclosporine's effect on coronaviruses, particularly SARS-CoV and MERS-CoV, have also taken place. Here, too, there was in vitro inhibition of viral RNA replication. Similar effects were observed with other coronaviruses, such as human coronavirus type 229E, transmissible gastroenteritis virus (TGEV), feline coronavirus (FCoV), porcine epidemic diarrhea virus (PEDV), and mouse hepatitis virus (MHV). These promising results led to the idea of using cyclosporine in the treatment of diseases caused by coronaviruses.
Discussion and Conclusion
Currently, there are no available studies examining the effect of cyclosporine on the SARS-CoV-2 virus. We can only assume that patients using it for the treatment of autoimmune diseases could benefit from its antiviral activity. However, the question remains whether this might negatively affect the development of antibody immunity against COVID-19.
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Sources:
1. Rudnicka L., Glowacka P., Goldust M. et al. Cyclosporine therapy during the COVID-19 pandemic. J Am Acad Dermatol 2020; 83 (2): 151–152, doi: 10.1016/j.jaad.2020.04.153.
2. SPC Ciclosporin Sandoz. Available at: www.sukl.cz/modules/medication/download.php?file=SPC154969.pdf&type=spc&as=ciclosporin-sandoz-spc
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