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

  1. Orth, Hans Martin
  2. Flasshove, Charlotte
  3. Berger, Moritz
  4. Hattenhauer, Tessa
  5. Biederbick, Kaja D.
  6. Mispelbaum, Rebekka
  7. Klein, Uwe
  8. Stemler, Jannik
  9. Fisahn, Matthis
  10. Doleschall, Anna D.
  11. Baermann, Ben-Niklas
  12. Koenigshausen, Eva
  13. Tselikmann, Olga
  14. Killer, Alexander
  15. de Angelis, Clara
  16. Gliga, Smaranda
  17. Stegbauer, Johannes
  18. Spuck, Nikolai
  19. Silling, Gerda
  20. Rockstroh, Jürgen K.
  21. Strassburg, Christian P.
  22. Brossart, Peter
  23. Panse, Jens P.
  24. Jensen, Björn-Erik Ole
  25. Luedde, Tom
  26. Boesecke, Christoph
  27. Heine, Annkristin
  28. Cornely, Oliver A.
  29. Monin, Malte ORCID logo

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WeightNameValue
1000 Titel
  • Early combination therapy of COVID-19 in high-risk patients
1000 Autor/in
  1. Orth, Hans Martin |
  2. Flasshove, Charlotte |
  3. Berger, Moritz |
  4. Hattenhauer, Tessa |
  5. Biederbick, Kaja D. |
  6. Mispelbaum, Rebekka |
  7. Klein, Uwe |
  8. Stemler, Jannik |
  9. Fisahn, Matthis |
  10. Doleschall, Anna D. |
  11. Baermann, Ben-Niklas |
  12. Koenigshausen, Eva |
  13. Tselikmann, Olga |
  14. Killer, Alexander |
  15. de Angelis, Clara |
  16. Gliga, Smaranda |
  17. Stegbauer, Johannes |
  18. Spuck, Nikolai |
  19. Silling, Gerda |
  20. Rockstroh, Jürgen K. |
  21. Strassburg, Christian P. |
  22. Brossart, Peter |
  23. Panse, Jens P. |
  24. Jensen, Björn-Erik Ole |
  25. Luedde, Tom |
  26. Boesecke, Christoph |
  27. Heine, Annkristin |
  28. Cornely, Oliver A. |
  29. Monin, Malte |
1000 Verlag
  • Springer Berlin Heidelberg
1000 Erscheinungsjahr 2023
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2023-11-29
1000 Erschienen in
1000 Quellenangabe
  • 52(3):877-889
1000 Copyrightjahr
  • 2023
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s15010-023-02125-5 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11142969/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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<jats:sup>6</jats:sup> copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10<jats:sup>6</jats:sup> 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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10<jats:sup>6</jats:sup> copies/ml of 8.0 days (IQR 6.0–15.3). Underlying haematological malignancies (HM) (<jats:italic>p</jats:italic> = 0.03) and treatment initiation later than five days after diagnosis (<jats:italic>p</jats:italic> &lt; 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (<jats:italic>n</jats:italic> = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2–9.9; <jats:italic>p</jats:italic> = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>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.</jats:p> </jats:sec>
1000 Sacherschließung
gnd 1206347392 COVID-19
lokal Viral Load/drug effects [MeSH]
lokal Aged [MeSH]
lokal Antibodies, Monoclonal/therapeutic use [MeSH]
lokal Immunocompromised host
lokal SARS-CoV-2/drug effects [MeSH]
lokal Ritonavir/therapeutic use [MeSH]
lokal Individualized therapeutic approaches
lokal COVID-19 Drug Treatment [MeSH]
lokal Male [MeSH]
lokal Virus Shedding/drug effects [MeSH]
lokal Drug Therapy, Combination [MeSH]
lokal Alanine/analogs
lokal Prolonged viral shedding
lokal Female [MeSH]
lokal Cytidine/analogs
lokal COVID-19/virology [MeSH]
lokal Adult [MeSH]
lokal Alanine/therapeutic use [MeSH]
lokal Humans [MeSH]
lokal Retrospective Studies [MeSH]
lokal Middle Aged [MeSH]
lokal COVID-19
lokal Hydroxylamines [MeSH]
lokal Adenosine Monophosphate/analogs
lokal Adenosine Monophosphate/therapeutic use [MeSH]
lokal Dual anti-SARS-CoV-2 therapies
lokal Research
lokal Antiviral Agents/therapeutic use [MeSH]
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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  1. Early combination therapy of COVID-19 in high-risk patients
    Early combination therapy of COVID-19 in high-risk patients
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