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Early combination therapy of COVID-19 in high-risk patients.


Authors: Hans Martin Orth, Charlotte Flasshove, Moritz Berger, Sandra Tessa Hattenhauer, Kaja D Biederbick, Rebekka Mispelbaum, Uwe Klein, Jannik Stemler, Matthis Fisahn, Anna D 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 P Panse, Björn-Erik Ole Jensen, Tom Luedde, Christoph Boesecke, Annkristin Heine, Oliver A Cornely, Malte B Monin

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 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10 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 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.

© 2023. The Author(s).

PMID: 38017344

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