Mary Wilson
Well-known member
Published on Line: 16 November 2021
https://doi.org/10.1038/s41467-021-26884-7
Jolien Van Cleemput 1✉, Willem van Snippenberg 1,17, Laurens Lambrechts 1,2,17, Amélie Dendooven3,4,5, Valentino D’Onofrio 6,7, Liesbeth Couck 8, Wim Trypsteen 1, Jan Vanrusselt9, Sebastiaan Theuns10,11, Nick Vereecke 10,11, Thierry P. P. van den Bosch12, Martin Lammens4,5, Ann Driessen4,5, Ruth Achten4,5,13, Ken R. Bracke 14, Wim Van den Broeck8, Jan Von der Thüsen 12, Hans Nauwynck11, Jo Van Dorpe 3, Sarah Gerlo1,15, Piet Maes 16, Janneke Cox6,7 & Linos Vandekerckhov
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 immunocom- promised 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 mea- sures need to be tailored to specific needs of immunocompromised patients, even when respiratory symptoms cease.
https://www.nature.com/articles/s41467-021-26884-7.pdf
https://doi.org/10.1038/s41467-021-26884-7
Jolien Van Cleemput 1✉, Willem van Snippenberg 1,17, Laurens Lambrechts 1,2,17, Amélie Dendooven3,4,5, Valentino D’Onofrio 6,7, Liesbeth Couck 8, Wim Trypsteen 1, Jan Vanrusselt9, Sebastiaan Theuns10,11, Nick Vereecke 10,11, Thierry P. P. van den Bosch12, Martin Lammens4,5, Ann Driessen4,5, Ruth Achten4,5,13, Ken R. Bracke 14, Wim Van den Broeck8, Jan Von der Thüsen 12, Hans Nauwynck11, Jo Van Dorpe 3, Sarah Gerlo1,15, Piet Maes 16, Janneke Cox6,7 & Linos Vandekerckhov
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 immunocom- promised 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 mea- sures need to be tailored to specific needs of immunocompromised patients, even when respiratory symptoms cease.
https://www.nature.com/articles/s41467-021-26884-7.pdf
