What are the salvage therapy options for persistent Coronavirus disease (COVID-19) in an immunocompromised patient?

From the Guidelines

For immunocompromised patients with persistent COVID-19 infection, the use of dexamethasone during the inflammatory phase of the disease is recommended, as evidenced by the 2022 study from the European Conference on Infections in Leukaemia (ECIL 9) 1. This approach is based on the potential benefits of reducing inflammation in patients with oxygen requirements and increased inflammatory markers. The following key points should be considered:

• Dexamethasone should be used at a dose of 6 mg daily for 10 days in patients with oxygen therapy, as shown to reduce mortality in the RECOVERY trial 1.
• The use of immunomodulatory therapies, such as anti-IL-6 monoclonal antibodies, should be considered with caution, as their effects on the course of disease in already immunosuppressed patients are poorly understood 1.
• Other immunosuppressive drugs, such as baracitinib, tofacinib, and colchicine, may have some benefit in clinical recovery rates, but their use should be carefully evaluated in the context of the patient's underlying condition 1.
• The use of anti-SARS-CoV-2 monoclonal antibodies, such as casirivimab/imdevimab, and convalescent plasma may be considered in specific cases, but their effectiveness may vary depending on the circulating variant and the patient's immune response 1.
• Close monitoring with serial SARS-CoV-2 PCR testing is essential to assess treatment response and adjust therapy as needed. Some key considerations for salvage therapy in immunocompromised patients with persistent COVID-19 infection include:
• Reducing immunosuppressive medications when possible, in consultation with specialists managing the patient's underlying condition.
• Using a combination of therapies, such as antiviral medications and immunomodulatory agents, to target different aspects of the disease.
• Carefully evaluating the potential risks and benefits of each therapy, given the patient's underlying condition and the potential for drug interactions.

From the FDA Drug Label

VEKLURY is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients (birth to less than 18 years of age weighing at least 1. 5 kg) who are: Hospitalized, or Not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death. For hospitalized patients requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days. For hospitalized patients not requiring invasive mechanical ventilation and/or ECMO, the recommended treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days for a total treatment duration of up to 10 days.

The use of remdesivir as a salvage therapy for persistent COVID-19 in immunocompromised patients is not directly addressed in the provided drug label. However, the label does provide guidance on the treatment of COVID-19 in hospitalized patients, including those who may be immunocompromised.

• The recommended treatment duration for hospitalized patients can be up to 10 days.
• Treatment may be extended for up to 5 additional days if a patient does not demonstrate clinical improvement. It is essential to note that the decision to use remdesivir as a salvage therapy should be made on a case-by-case basis, considering the individual patient's clinical circumstances and medical history 2.

From the Research

Salvage Therapy for Persistent COVID-19 in Immunocompromised Patients

• The use of sequential or combination treatments, including antivirals and monoclonal antibodies, has been explored as a potential salvage therapy for persistent COVID-19 in immunocompromised patients 3, 4.
• A case series study found that 93% of immunocompromised patients with persistent SARS-CoV-2 infection achieved complete virological response after receiving sequential or combination regimens, including antivirals and/or monoclonal antibodies 3.
• Another study suggested that combination therapies, including small molecule antivirals and passive immunotherapies, may be safe and effective in treating persistent COVID-19 in immunocompromised patients 4.
• A systematic review found that combination therapy with at least two direct antiviral agents resulted in a viral clearance rate of 79%, with a 16% recurrence rate, and an all-cause mortality rate of 9% 5.

Treatment Options

• Antiviral therapies, such as remdesivir, nirmatrelvir/ritonavir, and molnupiravir, have been used to treat persistent COVID-19 in immunocompromised patients 3, 5, 6.
• Monoclonal antibodies, such as tixagevimab/cilgavimab and sotrovimab, have also been used in combination with antivirals to treat persistent COVID-19 in immunocompromised patients 3, 4.
• Corticosteroids, such as dexamethasone, have been used to treat severe or critical COVID-19, and may be used in combination with other therapies 7.

Efficacy and Safety

• The efficacy and safety of antiviral therapies for persistent COVID-19 in immunocompromised patients have been evaluated in several studies, with varying results 3, 4, 5.
• A systematic review found that the evidence certainty for the efficacy and safety of antiviral therapies was very low, highlighting the need for further studies 5.
• Adverse events have been reported in some studies, including those using combination therapies with at least two direct antiviral agents 5.