Antiviral combination therapy in severely immunocompromised patients with persistent or recurrent COVID-19

Antiviral agents are the primary treatment for coronavirus disease 2019 (COVID-19). Severely immunocompromised patients may experience persistent illnesses or multiple recurrences despite antiviral therapy, and optimal management remains unclear. We evaluated the efficacy of conventional monotherapy versus combination antiviral therapy in this population.

This single-center, retrospective cohort study enrolled severely immunocompromised patients with COVID-19 in whom initial therapy failed post-diagnosis. The success rates of conventional monotherapy and combination therapy in the second and later courses were evaluated. Combination therapy was defined as the sequential or concurrent use of ≥2 antiviral agents. Factors associated with treatment success were evaluated using a generalized linear mixed model.

Of the 23 enrolled patients, 87.0 % had hematologic malignancies and 69.6 % were receiving B-cell-depleting therapy. After initial treatment failure, patients received between two and six additional courses. Of the 34 courses, 22 were conventional monotherapy and 12 were combination therapy; overall success rates were 50.0 % and 91.7 %, respectively. Considering only the second course, success rates were 56.3 % for monotherapy and 100 % for combination therapy. The median (range) treatment durations were 5 days (3-10) for monotherapy and 10 days (10-25) for combination therapy. Each agent was administered consecutively for its approved duration. Combination therapy was associated with treatment success (p = 0.036).

Subsequent conventional monotherapy failed in approximately half of severely immunocompromised patients who experienced treatment failure on the initial COVID-19 treatment. Antiviral combination therapy has a high clinical success rate and may be useful.