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Title: | Organ-specific genome diversity of replication-competent SARS-CoV-2 | Authors: | Van Cleemput, Jolien van Snippenberg, Willem Lambrechts, Laurens Dendooven, Amelie D'ONOFRIO, Valentino Couck, Liesbeth Trypsteen, Wim Vanrusselt, Jan Theuns, Sebastiaan Vereecke, Nick van den Bosch, Thierry P. P. Lammens, Martin DRIESSEN, Ann ACHTEN, Ruth Bracke, Ken R. VAN DEN BROECK, Wim Von der Thusen, Jan Nauwynck, Hans Van Dorpe, Jo Gerlo, Sarah Maes, Piet COX, Janneke Vandekerckhove, Linos |
Issue Date: | 2021 | Publisher: | NATURE PORTFOLIO | Source: | NATURE COMMUNICATIONS, 12 (1) (Art N° 6612) | Abstract: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not always confined to the respiratory system, as it impacts people on a broad clinical spectrum from asymptomatic to severe systemic manifestations resulting in death. Further, accumulation of intra-host single nucleotide variants during prolonged SARS-CoV-2 infection may lead to emergence of variants of concern (VOCs). Still, information on virus infectivity and intra-host evolution across organs is sparse. We report a detailed virological analysis of thirteen postmortem coronavirus disease 2019 (COVID-19) cases that provides proof of viremia and presence of replication-competent SARS-CoV-2 in extrapulmonary organs of immunocompromised patients, including heart, kidney, liver, and spleen (NCT04366882). In parallel, we identify organ-specific SARS-CoV-2 genome diversity and mutations of concern N501Y, T1027I, and Y453F, while the patient had died long before reported emergence of VOCs. These mutations appear in multiple organs and replicate in Vero E6 cells, highlighting their infectivity. Finally, we show two stages of fatal disease evolution based on disease duration and viral loads in lungs and plasma. Our results provide insights about the pathogenesis and intra-host evolution of SARS-CoV-2 and show that COVID-19 treatment and hygiene measures need to be tailored to specific needs of immunocompromised patients, even when respiratory symptoms cease. Here the authors provide a detailed virological analysis of thirteen postmortem COVID-19 cases, including presence of replication-competent SARS-CoV-2 in extrapulmonary organs and tissue-specific patterns of SARS-CoV-2 genome diversity of an immunocompromised patient. | Notes: | Van Cleemput, J; Vandekerckhove, L (corresponding author), Univ Ghent, Ghent Univ Hosp, HIV Cure Res Ctr, Dept Internal Med & Pediat, Ghent, Belgium. jolien.vancleemput@ugent.be; linos.vandekerckhove@ugent.be |
Document URI: | http://hdl.handle.net/1942/36099 | e-ISSN: | 2041-1723 | DOI: | 10.1038/s41467-021-26884-7 | ISI #: | WOS:000719546000026 | Rights: | This article is licensed under a Creative Commons Attribution 4.0 International License. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
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s41467-021-26884-7.pdf | Published version | 7.98 MB | Adobe PDF | View/Open |
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