دورية أكاديمية
Early combination therapy of COVID-19 in high-risk patients.
| العنوان: | Early combination therapy of COVID-19 in high-risk patients. |
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| المؤلفون: | Orth HM; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Flasshove C; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Berger M; Institute for Medical Biometry, Informatics and Epidemiology, Bonn University Hospital, Venusberg-Campus 1, 53127, Bonn, Germany., Hattenhauer T; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Biederbick KD; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Mispelbaum R; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Klein U; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Stemler J; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department I of Internal Medicine, European Diamond Excellence Centre for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine, and University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Institute of Translational Research, Cologne Excellence Cluster On Cellular Stress Responses, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; German Centre for Infection Research (DZIF), Partner-Site Cologne-Bonn, Kerpener Str. 62, 50937, Cologne, Germany., Fisahn M; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department I of Internal Medicine, European Diamond Excellence Centre for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine, and University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Institute of Translational Research, Cologne Excellence Cluster On Cellular Stress Responses, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; German Centre for Infection Research (DZIF), Partner-Site Cologne-Bonn, Kerpener Str. 62, 50937, Cologne, Germany., Doleschall AD; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany., Baermann BN; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Hematology, Oncology, and Clinical Immunology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Koenigshausen E; Department of Nephrology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Tselikmann O; Department of Nephrology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Killer A; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., de Angelis C; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Gliga S; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Stegbauer J; Department of Nephrology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Spuck N; Institute for Medical Biometry, Informatics and Epidemiology, Bonn University Hospital, Venusberg-Campus 1, 53127, Bonn, Germany., Silling G; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany., Rockstroh JK; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; German Centre for Infection Research (DZIF), Partner-Site Cologne-Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Strassburg CP; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Brossart P; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Panse JP; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany., Jensen BO; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Luedde T; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany., Boesecke C; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; German Centre for Infection Research (DZIF), Partner-Site Cologne-Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Heine A; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Cornely OA; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany.; Department I of Internal Medicine, European Diamond Excellence Centre for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine, and University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Institute of Translational Research, Cologne Excellence Cluster On Cellular Stress Responses, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; German Centre for Infection Research (DZIF), Partner-Site Cologne-Bonn, Kerpener Str. 62, 50937, Cologne, Germany., Monin MB; Centre for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf, (ABCD), Aachen, Germany. malte_benedikt.monin@ukbonn.de.; Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany. malte_benedikt.monin@ukbonn.de.; German Centre for Infection Research (DZIF), Partner-Site Cologne-Bonn, Venusberg-Campus 1, 53127, Bonn, Germany. malte_benedikt.monin@ukbonn.de.; Johanniter-Kliniken Bonn GmbH, Johanniter-Krankenhaus Bonn, Bonn, Germany. malte_benedikt.monin@ukbonn.de. |
| المصدر: | Infection [Infection] 2024 Jun; Vol. 52 (3), pp. 877-889. Date of Electronic Publication: 2023 Nov 29. |
| نوع المنشور: | Journal Article; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Heidelberg Country of Publication: Germany NLM ID: 0365307 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1439-0973 (Electronic) Linking ISSN: 03008126 NLM ISO Abbreviation: Infection Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2011- : Heidelberg : Springer Heidelberg Original Publication: München, Verlagsgesellschaft Otto Spatz. |
| مواضيع طبية MeSH: | Antiviral Agents*/therapeutic use , COVID-19 Drug Treatment* , Drug Therapy, Combination* , SARS-CoV-2*/drug effects , COVID-19*/virology , Virus Shedding*/drug effects , Viral Load*/drug effects, Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Ritonavir/therapeutic use ; Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Alanine/analogs & derivatives ; Alanine/therapeutic use ; Adult ; Cytidine/analogs & derivatives ; Hydroxylamines |
| مستخلص: | 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. (© 2023. The Author(s).) |
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| فهرسة مساهمة: | Keywords: COVID-19; Dual anti-SARS-CoV-2 therapies; Immunocompromised host; Individualized therapeutic approaches; Prolonged viral shedding |
| المشرفين على المادة: | 0 (Antiviral Agents) O3J8G9O825 (Ritonavir) 415SHH325A (Adenosine Monophosphate) 3QKI37EEHE (remdesivir) 0 (Antibodies, Monoclonal) OF5P57N2ZX (Alanine) YA84KI1VEW (molnupiravir) 5CSZ8459RP (Cytidine) 0 (Hydroxylamines) |
| تواريخ الأحداث: | Date Created: 20231128 Date Completed: 20240601 Latest Revision: 20240719 |
| رمز التحديث: | 20240720 |
| مُعرف محوري في PubMed: | PMC11142969 |
| DOI: | 10.1007/s15010-023-02125-5 |
| PMID: | 38017344 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1439-0973 |
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| DOI: | 10.1007/s15010-023-02125-5 |