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

Autor:	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.
Předmět:	THERAPEUTIC use of monoclonal antibodies RISK assessment COMBINATION drug therapy EARLY medical intervention VIRAL physiology IMMUNOCOMPROMISED patients FISHER exact test RETROSPECTIVE studies DESCRIPTIVE statistics ANTIVIRAL agents KAPLAN-Meier estimator ODDS ratio RESEARCH COMPARATIVE studies GENETIC mutation COVID-19 DRUG synergism REGRESSION analysis
Zdroj:	Infection; Jun2024, Vol. 52 Issue 3, p877-889, 13p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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