Could Isotretinoin Reduce the Risk for SARS-CoV-2 Infection?

Is acne treatment with isotretinoin associated with a reduced risk for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19)? In a letter to the editor published in Dermatologic Therapy, Lamia Hamouda Elgarhy, MD, of Tanta University in Egypt, explored this theory.

Isotretinoin, a retinoic acid derivative frequently prescribed to treat acne vulgaris, down-regulates ACE 2 receptors. These receptors are susceptible to SARS-CoV-2 infection as they help facilitate entry and replication of the virus into cells. Patients with hypertension and diabetes may be at an increased risk for COVID-19, as treatments for these diseases, including angiotensin II type-1 receptor blockers, may increase the expression of ACE2.

As isotretinoin has been demonstrated to down-regulate ACE 2 receptors, Dr Elgarhy suggested this treatment may reduce or prevent the cellular entry of SARS-CoV-2. The elderly, which represent the most vulnerable patient population, are less likely to take isotretinoin, considering acne is a disease that primarily affects adolescents and young adults. Whether treatment with isotretinoin can reduce the risk for infection in patients with metabolic comorbidities or in the elderly remains to be seen.

Isotretinoin may also inhibit papain like protease (PLpro), a protein encoded by SARS-CoV-2 genes. This protein is considered a deubiquitinating enzyme which modulates “the host cell ubiquitination machinery to the advantage of the virus,” wrote Dr Elgarhy. Based on current evidence, PLpro could represent a potential target in treatment of the virus. Isotretinoin may also increase CD4 counts and decrease viremia, as previously demonstrated in patients with HIV. In addition, isotretinoin may reduce inflammation and increase different immune mechanisms.

Although evidence to support isotretinoin’s role in potential COVID-19 treatment research exists, Dr Elgarhy noted that further in vitro and in vivo studies are needed to determine whether the acne treatment could effectively lower the risk of SARS-CoV-2 infection.

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Reference

Elgarhy LH. Could patients taking isotretinoin therapy be immune against SARS-COV-2? [published online May 13, 2020]. Dermatol Ther. doi: 10.1111/dth.13573