Successful Combination Treatment for Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Abstract

To theEditor—We read with interest the case report by Trottier and colleagues about successfully combining 20 days of nirmatrelvir/ritonavir and remdesivir for treatment of persistent coronavirus disease 2019 (COVID-19), published online in Clinical Infectious Diseases [1]. Another recent publication reported success with a combination of monoclonal antibodies, 7 days of remdesivir, and 5 days of nirmatrelvir/ritonavir [2]. Influenced by the report from Trottier et al, we started using combination treatment in our tertiary referral center and can now report similar outcomes. Eligible for combination treatment are patients who have tested polymerase chain reaction (PCR) positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for at least 6 weeks despite having received at least 1 course of antiviral treatment, and either have ongoing respiratory symptoms or are being planned to receive severe immunosuppressive treatment (Table 1). The patient with the longest follow-up, 2 months, is an 80-year-old man with follicular lymphoma treated with 6 cycles of obinituzumab and bendamustine between April and July 2022. Five weeks later he was admitted to our department due to fever and dyspnea. SARS-CoV-2 PCR was positive for Omicron BA.2 both in serum and nasopharynx. Chest computed tomography revealed bilateral diffuse ground-glass infiltrates with incipient fibrosis. During a 7-week-long hospital stay, antiviral treatment with tixagevimab/cilgavimab, 3 doses of convalescent plasma, and 2 treatment episodes with nirmatrelvir/ritonavir (8 and 5 days, respectively) had little effect on SARS-CoV-2 cycle threshold values, which never exceeded 25 (GeneXpert). At this time, total B-lymphocyte count was <0.01 × 109 cells/L and total T-cell count was 0.09 × 109 cells/L. Despite treatment with both local and systemic corticosteroids, lung function deteriorated, and the patient was discharged home with 3 L/minute of supplemental oxygen. Five weeks later, encouraged by the case report by Trottier et al [1], the patient was readmitted and treated with nirmatrelvir/ritonavir and remdesivir for 14 days. SARS-CoV-2 PCR was positive in serum and nasopharynx both at admission and after 9 days of treatment, why treatment was prolonged from the planned 10 days to 14 days. The patient became PCR negative day 14 and has now been negative for 2 months with a slowly improving lung function and only requires supplemental oxygen at physical activity. Local Protocol for the Treatment of Prolonged COVID-19 in Patients With Severe Immunosuppression at the Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden Abbreviations: COVID-19, coronavirus disease 2019; Ct, cycle threshold; GFR, glomerular filtration rate; IgG, immunoglobulin G; NOAC, novel oral anticoagulant; NPH, nasopharynx; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. We have been involved in combination treatment of persistent COVID-19 in 4 additional severely immunocompromised patients. All have turned SARS-CoV-2 PCR negative after 10–14 days of combination treatment, but a longer follow-up period is needed to rule out viral rebound. Persistent COVID-19 infection in immunocompromised patients is difficult to treat, with risk for development of antiviral resistance [4, 5]. Our experience together with recent case reports indicates that combination treatment with nirmatrelvir/ritonavir and remdesivir might be a promising approach [1–3]. The optimal treatment duration needs to be established but most likely has to be individualized; in our patient the 10-day treatment needed to be extended to 14 days, while others have reported both shorter and longer treatments [1–3]. Author Contributions. T. T. and J. V. participated in the care of the patients. O. B. and P. N. wrote the first versions of the manuscript, and all authors have revised the manuscript.

Topics & Concepts