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

• Published in: Infection 2024-06, Vol.52 (3), p.877-889
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - therapeutic use; Adult; Aged; Alanine - analogs & derivatives; Alanine - therapeutic use; Antibodies, Monoclonal - therapeutic use; Antiviral agents; Antiviral Agents - therapeutic use; Coronaviruses; COVID-19; COVID-19 - virology; COVID-19 Drug Treatment; Cytidine - analogs & derivatives; Drug Therapy, Combination; Family Medicine; Female; General Practice; Health services; Humans; Hydroxylamines; Immunocompromised hosts; Infectious Diseases; Internal Medicine; Male; Malignancy; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Patients; Rank tests; Regression analysis; Retrospective Studies; Risk; Risk groups; Ritonavir; Ritonavir - therapeutic use; SARS-CoV-2 - drug effects; Severe acute respiratory syndrome coronavirus 2; Synergistic effect; Toxicity; Viral diseases; Viral Load - drug effects; Virus Shedding - drug effects
• ISSN: 0300-8126; 1439-0973; 1439-0973
• DOI: 10.1007/s15010-023-02125-5

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