Background
Nirmatrelvir/ritonavir (N/r) is approved for the outpatient treatment of COVID-19 within 5 days of symptom onset and is typically used in patients at increased risk for severe disease. In severely immunocompromised patients, COVID-19 occasionally evolves into a chronic infection. The potential value of N/r in this context including optimal treatment duration is unknown. We describe the off-label use of N/r in severely immunocompromised patients with persistent COVID-19 related symptoms and viremia.
Methods
Data from patients in care at Erasmus University Medical Center in Rotterdam, the Netherlands, were collected when 1. immunocompromised, 2. SARS-CoV-2 PCR positive (>10.500 IU/ml) with persisting symptoms ≥7 days and 3. treated with N/r. Viral clearance (VC) was defined as a viral load <10,500 IU/ml without occurrence of viral rebound. Underlying immunocompromising condition, time from symptom onset, time to confirmed VC, percentage of patients with VC 28 days after treatment initiation, additional antiviral therapies and mortality were registered.
Results
Between November 2022 and March 2024, 16 immunocompromised patients with persistent COVID-19 were treated with off-label N/r with a median symptom duration of 53 days (IQR 31-75). 12/16 received N/r for 5 and 4/16 for 10 days. In 10/16, N/r was combined with COVID-19 convalescent plasma. 7/16 were hospitalized at N/r initiation (1 at ICU). Despite the long-lasting infection, the median time to confirmed VC was very short at 7 days (IQR 6–23). VC was observed in 12/16 within 28 days after treatment initiation and in 13/16 within 60 days. 2/4 patients with a viral rebound successfully received a second course of N/r at day 20 (10-day course) and 77 (5-day course), followed by VC at day 23 and 98, respectively. One of the 16 patients died from COVID-19-related ARDS on day 4 post-treatment; all others were alive at day 60. Figure 1 illustrates virological treatment response of all 16 patients.
Conclusions
In severely immunocompromised patients with non-resolving COVID-19, off-label treatment with N/r resulted in prompt viral clearance in 75%. Whether the simultaneous use of CCP in 10 of 16 patients contributed to this result needs further study. Well-designed studies in this patient group are urgently needed to compare watchful waiting with different (combinations) of drugs as well as treatment durations.
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