دورية أكاديمية
Rapid Selection of Sotrovimab Escape Variants in Severe Acute Respiratory Syndrome Coronavirus 2 Omicron-Infected Immunocompromised Patients.
| العنوان: | Rapid Selection of Sotrovimab Escape Variants in Severe Acute Respiratory Syndrome Coronavirus 2 Omicron-Infected Immunocompromised Patients. |
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| المؤلفون: | Gliga S; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.; Institute of Virology, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Lübke N; Institute of Virology, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Killer A; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Gruell H; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Walker A; Institute of Virology, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Dilthey AT; Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Thielen A; Institute of Immunology and Genetics, Kaiserslautern, Germany., Lohr C; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Flaßhove C; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Krieg S; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Pereira JV; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Seraphin TP; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Zaufel A; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Däumer M; Institute of Immunology and Genetics, Kaiserslautern, Germany., Orth HM; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Feldt T; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Bode JG; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Klein F; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Timm J; Institute of Virology, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Luedde T; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Jensen BO; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. |
| المصدر: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2023 Feb 08; Vol. 76 (3), pp. 408-415. |
| نوع المنشور: | Journal Article; Observational Study; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Oxford : Oxford University Press Original Publication: Chicago, IL : The University of Chicago Press, c1992- |
| مواضيع طبية MeSH: | COVID-19* , SARS-CoV-2*/genetics, Humans ; Antibodies, Neutralizing ; Antibodies, Viral ; Immunocompromised Host ; Prospective Studies ; RNA, Viral |
| مستخلص: | Background: Monoclonal antibodies (mAbs) that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly less effective against Omicron variants. Immunocompromised patients often experience prolonged viral shedding, resulting in an increased risk of viral escape. Methods: In an observational, prospective cohort, 57 patients infected with Omicron variants who received sotrovimab alone or in combination with remdesivir were followed. The study end points were a decrease in SARS-CoV-2 RNA <106 copies/mL in nasopharyngeal swabs at day 21 and the emergence of escape mutations at days 7, 14, and 21 after sotrovimab administration. All SARS-CoV-2 samples were analyzed using whole-genome sequencing. Individual variants within the quasispecies were subsequently quantified and further characterized using a pseudovirus neutralization assay. Results: The majority of patients (43 of 57, 75.4%) were immunodeficient, predominantly due to immunosuppression after organ transplantation or hematologic malignancies. Infections by Omicron/BA.1 comprised 82.5%, while 17.5% were infected by Omicron/BA.2. Twenty-one days after sotrovimab administration, 12 of 43 (27.9%) immunodeficient patients had prolonged viral shedding compared with 1 of 14 (7.1%) immunocompetent patients (P = .011). Viral spike protein mutations, some specific for Omicron (e.g., P337S and/or E340D/V), emerged in 14 of 43 (32.6%) immunodeficient patients, substantially reducing sensitivity to sotrovimab in a pseudovirus neutralization assay. Combination therapy with remdesivir significantly reduced emergence of escape variants. Conclusions: Immunocompromised patients face a considerable risk of prolonged viral shedding and emergence of escape mutations after early therapy with sotrovimab. These findings underscore the importance of careful monitoring and the need for dedicated clinical trials in this patient population. Competing Interests: Potential conflicts of interest. N. L. received honoraria for presentations from Gilead, MSD, AbbVie, and ViiV (outside the submitted work) and served on advisory boards for ViiV and Theratechnologies (outside the submitted work), including consulting fees from ViiV and Theratechnologies. B.-E. O. J. received honoraria for presentations from Gilead, GSK, Falk, Janssen-Cilag, ViiV, and Fresenius Medical Care (outside the submitted work); received travel support from Gilead; served on advisory boards for ViiV, Gilead, and Theratechnologies (outside the submitted work); received consulting fees from Gilead, ViiV, and Theratechnologies; was involved in the development of the national recommendation on COVID-19 treatment by COVRIIN (COVID-19 Expert Group at the Robert Koch Institute - National Public Health Institute of Germany) (unpaid participation). T. F. was principal investigator (PI) for a Gilead clinical trial and served on Gilead advisory boards (outside the submitted work); was PI for the SIMPLE trials (Study to Evaluate the Safety and Antiviral Activity of Remdesivir in Participants with Moderate Coronavirus Disease (COVID-19) Compared to Standard of Care Treatment) (no personal fees); authored a publication on remdesivir (Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med 2020; 382(24):2327–36. doi: 10.1056/NEJMoa2007016; authorships among others including Gilead team members; no personal fees) was involved in the development of the national recommendation on COVID-19 treatment by COVRIIN (COVID-19 Expert Group at the Robert Koch Institute – National Public Health Institute of Germany. T. L. received honoraria for lectures from AbbVie, BMS, and Gilead; received travel support from Gilead and AbbVie; served on advisory boards for Gilead; received honoraria for presentations from AbbVie, BMS, and Gilead; and received travel support from Gilead and AbbVie. H. G. and F. K. are listed as inventors on patent applications for SARS-CoV-2 neutralizing antibodies filed by the University of Cologne. A. K. received lecture fees from Gilead, participated on advisory boards for Gilead, and was supported by AbbVie for attending meetings. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.) |
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| فهرسة مساهمة: | Keywords: Omicron; SARS-CoV-2; escape; immunodeficiency; sotrovimab |
| المشرفين على المادة: | 0 (Antibodies, Neutralizing) 0 (Antibodies, Viral) 0 (RNA, Viral) 1MTK0BPN8V (sotrovimab) |
| SCR Organism: | SARS-CoV-2 variants |
| تواريخ الأحداث: | Date Created: 20221003 Date Completed: 20230214 Latest Revision: 20230220 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9619606 |
| DOI: | 10.1093/cid/ciac802 |
| PMID: | 36189631 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1537-6591 |
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| DOI: | 10.1093/cid/ciac802 |