دورية أكاديمية
SARS-CoV-2 evolution during prolonged infection in immunocompromised patients.
| العنوان: | SARS-CoV-2 evolution during prolonged infection in immunocompromised patients. |
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| المؤلفون: | Marques AD; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Graham-Wooten J; Division of Pulmonary, Allergy, and Critical Care, Philadelphia, Pennsylvania, USA., Fitzgerald AS; Division of Pulmonary, Allergy, and Critical Care, Philadelphia, Pennsylvania, USA., Sobel Leonard A; Division of Infectious Diseases, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Cook EJ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Everett JK; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Rodino KG; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Moncla LH; Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Kelly BJ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Collman RG; Division of Pulmonary, Allergy, and Critical Care, Philadelphia, Pennsylvania, USA., Bushman FD; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. |
| المصدر: | MBio [mBio] 2024 Mar 13; Vol. 15 (3), pp. e0011024. Date of Electronic Publication: 2024 Feb 16. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Society for Microbiology |
| مواضيع طبية MeSH: | SARS-CoV-2* , COVID-19*, Humans ; Antibodies, Monoclonal ; Genome, Viral ; Immunocompromised Host |
| مستخلص: | Prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients provides an opportunity for viral evolution, potentially leading to the generation of new pathogenic variants. To investigate the pathways of viral evolution, we carried out a study on five patients experiencing prolonged SARS-CoV-2 infection (quantitative polymerase chain reaction-positive for 79-203 days) who were immunocompromised due to treatment for lymphoma or solid organ transplantation. For each timepoint analyzed, we generated at least two independent viral genome sequences to assess the heterogeneity and control for sequencing error. Four of the five patients likely had prolonged infection; the fifth apparently experienced a reinfection. The rates of accumulation of substitutions in the viral genome per day were higher in hospitalized patients with prolonged infection than those estimated for the community background. The spike coding region accumulated a significantly greater number of unique mutations than other viral coding regions, and the mutation density was higher. Two patients were treated with monoclonal antibodies (bebtelovimab and sotrovimab); by the next sampled timepoint, each virus population showed substitutions associated with monoclonal antibody resistance as the dominant forms ( spike K444N and spike E340D). All patients received remdesivir, but remdesivir-resistant substitutions were not detected. These data thus help elucidate the trends of emergence, evolution, and selection of mutational variants within long-term infected immunocompromised individuals. Importance: SARS-CoV-2 is responsible for a global pandemic, driven in part by the emergence of new viral variants. Where do these new variants come from? One model is that long-term viral persistence in infected individuals allows for viral evolution in response to host pressures, resulting in viruses more likely to replicate efficiently in humans. In this study, we characterize replication in several hospitalized and long-term infected individuals, documenting efficient pathways of viral evolution. Competing Interests: The authors declare no conflict of interest. |
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| معلومات مُعتمدة: | P30 AI045008 United States AI NIAID NIH HHS; R61 HL137063 United States HL NHLBI NIH HHS; R33 HL137063 United States HL NHLBI NIH HHS; K23 AI121485 United States AI NIAID NIH HHS; R01 AI140442 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: COVID-19; SARS-CoV-2; coronavirus; long-term infection; prolonged infection |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) |
| تواريخ الأحداث: | Date Created: 20240216 Date Completed: 20240314 Latest Revision: 20240315 |
| رمز التحديث: | 20240315 |
| مُعرف محوري في PubMed: | PMC10936176 |
| DOI: | 10.1128/mbio.00110-24 |
| PMID: | 38364100 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2150-7511 |
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| DOI: | 10.1128/mbio.00110-24 |