학술논문
Early combination therapy of COVID-19 in high-risk patients
Document Type
Original Paper
Author
Orth, Hans Martin; Flasshove, Charlotte; Berger, Moritz; Hattenhauer, Tessa; Biederbick, Kaja D.; Mispelbaum, Rebekka; Klein, Uwe; Stemler, Jannik; Fisahn, Matthis; Doleschall, Anna D.; Baermann, Ben-Niklas; Koenigshausen, Eva; Tselikmann, Olga; Killer, Alexander; de Angelis, Clara; Gliga, Smaranda; Stegbauer, Johannes; Spuck, Nikolai; Silling, Gerda; Rockstroh, Jürgen K.; Strassburg, Christian P.; Brossart, Peter; Panse, Jens P.; Jensen, Björn-Erik Ole; Luedde, Tom; Boesecke, Christoph; Heine, Annkristin; Cornely, Oliver A.; Monin, Malte B.
Source
Infection: A Journal of Infectious Diseases. 52(3):877-889
Subject
Language
English
ISSN
0300-8126
1439-0973
1439-0973
Abstract
Purpose: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect.Methods: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 106 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 106 copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher’s tests or Kaplan−Meier analysis and long-rank tests. Multivariable regression analysis was performed.Results: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 106 copies/ml of 8.0 days (IQR 6.0–15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2–9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment.Conclusion: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.