tetano
Editor, Senior Moderator
Nat Commun
. 2021 Nov 16;12(1):6612.
doi: 10.1038/s41467-021-26884-7.
Organ-specific genome diversity of replication-competent SARS-CoV-2
Jolien Van Cleemput[SUP] 1 [/SUP], Willem van Snippenberg[SUP] #[/SUP][SUP] 2 [/SUP], Laurens Lambrechts[SUP] #[/SUP][SUP] 2 3 [/SUP], Amélie Dendooven[SUP] 4 5 6 [/SUP], Valentino D'Onofrio[SUP] 7 8 [/SUP], Liesbeth Couck[SUP] 9 [/SUP], Wim Trypsteen[SUP] 2 [/SUP], Jan Vanrusselt[SUP] 10 [/SUP], Sebastiaan Theuns[SUP] 11 12 [/SUP], Nick Vereecke[SUP] 11 12 [/SUP], Thierry P P van den Bosch[SUP] 13 [/SUP], Martin Lammens[SUP] 5 6 [/SUP], Ann Driessen[SUP] 5 6 [/SUP], Ruth Achten[SUP] 5 6 14 [/SUP], Ken R Bracke[SUP] 15 [/SUP], Wim Van den Broeck[SUP] 9 [/SUP], Jan Von der Thüsen[SUP] 13 [/SUP], Hans Nauwynck[SUP] 12 [/SUP], Jo Van Dorpe[SUP] 4 [/SUP], Sarah Gerlo[SUP] 2 16 [/SUP], Piet Maes[SUP] 17 [/SUP], Janneke Cox[SUP] 7 8 [/SUP], Linos Vandekerckhove[SUP] 18 [/SUP]
Affiliations
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.
. 2021 Nov 16;12(1):6612.
doi: 10.1038/s41467-021-26884-7.
Organ-specific genome diversity of replication-competent SARS-CoV-2
Jolien Van Cleemput[SUP] 1 [/SUP], Willem van Snippenberg[SUP] #[/SUP][SUP] 2 [/SUP], Laurens Lambrechts[SUP] #[/SUP][SUP] 2 3 [/SUP], Amélie Dendooven[SUP] 4 5 6 [/SUP], Valentino D'Onofrio[SUP] 7 8 [/SUP], Liesbeth Couck[SUP] 9 [/SUP], Wim Trypsteen[SUP] 2 [/SUP], Jan Vanrusselt[SUP] 10 [/SUP], Sebastiaan Theuns[SUP] 11 12 [/SUP], Nick Vereecke[SUP] 11 12 [/SUP], Thierry P P van den Bosch[SUP] 13 [/SUP], Martin Lammens[SUP] 5 6 [/SUP], Ann Driessen[SUP] 5 6 [/SUP], Ruth Achten[SUP] 5 6 14 [/SUP], Ken R Bracke[SUP] 15 [/SUP], Wim Van den Broeck[SUP] 9 [/SUP], Jan Von der Thüsen[SUP] 13 [/SUP], Hans Nauwynck[SUP] 12 [/SUP], Jo Van Dorpe[SUP] 4 [/SUP], Sarah Gerlo[SUP] 2 16 [/SUP], Piet Maes[SUP] 17 [/SUP], Janneke Cox[SUP] 7 8 [/SUP], Linos Vandekerckhove[SUP] 18 [/SUP]
Affiliations
- PMID: 34785663
- DOI: 10.1038/s41467-021-26884-7
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.