Several antivirals are available for the treatment of SARS-CoV-2 infection, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy.1 In this practical guide, we review the indications for these drugs and provide guidance on which dermatology patients with mild to moderate COVID-19 could benefit from their use.

Immunosuppressants and immunomodulators are widely used in dermatology, but a number of these drugs may increase the risk of severe COVID-19.2,3 New antivirals have been shown to reduce progression to severe COVID in patients on immunomodulators classified as high risk.4 The following immunomodulators, all frequently used in dermatology, have been classified as high risk by the AEMPS (Table 1): high-dose or long-term corticosteroids; immunosuppressive drugs administered in the previous 3 months; and certain immunomodulatory biologics administered in the previous 3 months (or previous 6 months in the case of anti-CD20 therapy). Patients on immune checkpoint inhibitors and other cancer treatments that do not increase infection risk, such as targeted therapy drugs for melanoma and hedgehog pathway inhibitors, are not eligible for new antivirals according to the AEMPS priority criteria (Table 1). Finally, there are many immunomodulatory drugs commonly used in dermatology on which the AEMPS has not taken a position (Table 2). Evidence of their safety in COVID is scarce, although reports to date do not seem to indicate an increased risk of progression to severe disease. Some authors have even proposed that some of these drugs may help curb the cytokine storm induced by the virus.5,6

New treatment options for SARS-CoV-2 infection can be divided into 2 classes (Table 3): antivirals and monoclonal antibodies. Antivirals include nirmatrelvir/ritonavir (Paxlovid), remdesivir (Veklury), and molnupiravir (Lagevrio), which block enzymes that are crucial to viral replication.7–9 Monoclonal antibodies include casirivimab/imdevimab (Ronapreve) and sotrovimab (Xevudy), which bind to different epitopes on the spike protein of SARS-CoV-2, preventing the virus from entering human cells.4,10 These drugs are indicated for all patients with mild to moderate COVID-19 who do not require hospital admission and who are being treated with any of the high-risk immunomodulators mentioned, regardless of vaccination status.

For adults (Fig. 1), the AEMPS recommends nirmatrelvir/ritonavir for 5 days as the treatment of choice because it is effective, easy to prescribe, and readily accessible. Drug-drug interactions are the main contraindication, as ritonavir is a strong inhibitor of cytochrome CYP3A.7 Choice of drug for patients in whom nirmatrelvir/ritonavir is contraindicated (Table 4) depends on immunoglobulin G titers against the SARS-CoV-2 spike protein. Monoclonal antibodies are the first-line option for patients with a titer of less than 260 binding antibody units per milliliter, while antivirals are indicated for patients with higher titers or for whom serology is not available. Choice of monoclonal antibody depends on the SARS-CoV-2 variant suspected. When omicron is suspected, the treatment of choice is sotrovimab, the only monoclonal antibody to have shown in vitro neutralizing activity against this variant.11 In other cases, casirivimab/imdevimab is used. The antiviral of choice is remdesivir. When this is not available, molnupiravir, an unauthorized drug with a use recommendation from the Committee for Medicinal Products for Human Use, can be used. Monoclonal antibodies and antivirals should both be started within 5 to 7 days of symptom onset.

Figure 1.

Treatment algorithm for new antivirals against SARS-CoV-2 in adults (adapted from Spanish Agency for Medicines and Medical Devices [AEMPS] guidance). BAU indicates binding antibody units; Ig, immunoglobulin.

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Remdesivir is also the treatment of choice for pediatric patients under the age of 12 years or weighing less than 40kg (Fig. 2). Classes of drugs other than monoclonal antibodies should be considered in patients whose condition is worsening despite remdesivir.

Figure 2.

Treatment algorithm for new antivirals against SARS-CoV-2 in pediatric patients (adapted from Spanish Agency for Medicines and Medical Devices [AEMPS] guidance).

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In conclusion, immunomodulators are a mainstay treatment for many patients in dermatology, where inflammatory and autoimmune disorders are common. Dermatologists must be familiar with the treatments available for SARS-CoV-2 infection, as some of their patients might be in a high-risk situation. We hope that this guide will help.