Early combination therapy of COVID-19 in high-risk patients
Hans Martin Orth, Charlotte Flasshove, Moritz Berger, Tessa Hattenhauer, Kaja D. Biederbick, Rebekka Mispelbaum, U. Klein, Jannik Stemler, Matthis Fisahn, Anna Dorottya Doleschall, Ben‐Niklas Baermann, Eva Koenigshausen, Olga Tselikmann, Alexander Killer, Clara de Angelis, Smaranda Gliga, Johannes Stegbauer, Nikolai Spuck, Gerda Silling, Jürgen K. Rockstroh, Christian P. Strassburg, Peter Brossart, Jens Panse, Björn‐Erik Ole Jensen, Tom Luedde, Christoph Boesecke, Annkristin Heine, Oliver A. Cornely, Malte B. Monin
Abstract
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 (≥ 10 6 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10 6 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 ≥ 10 6 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.