Cargando…

High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19

BACKGROUND: Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (S...

Descripción completa

Detalles Bibliográficos
Autores principales: Tveita, Anders, Murphy, Sarah Louise, Holter, Jan Cato, Kildal, Anders Benjamin, Michelsen, Annika E, Lerum, Tøri Vigeland, Kaarbø, Mari, Heggelund, Lars, Holten, Aleksander Rygh, Finbråten, Ane-Kristine, Müller, Karl Erik, Mathiessen, Alexander, Bøe, Simen, Fevang, Børre, Granerud, Beathe Kiland, Tonby, Kristian, Lind, Andreas, Dudman, Susanne Gjeruldsen, Henriksen, Katerina Nezvalova, Müller, Fredrik, Skjønsberg, Ole Henning, Trøseid, Marius, Barratt-Due, Andreas, Dyrhol-Riise, Anne Ma, Aukrust, Pål, Halvorsen, Bente, Dahl, Tuva Børresdatter, Ueland, Thor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384496/
https://www.ncbi.nlm.nih.gov/pubmed/35876699
http://dx.doi.org/10.1093/infdis/jiac313
_version_ 1784769441990443008
author Tveita, Anders
Murphy, Sarah Louise
Holter, Jan Cato
Kildal, Anders Benjamin
Michelsen, Annika E
Lerum, Tøri Vigeland
Kaarbø, Mari
Heggelund, Lars
Holten, Aleksander Rygh
Finbråten, Ane-Kristine
Müller, Karl Erik
Mathiessen, Alexander
Bøe, Simen
Fevang, Børre
Granerud, Beathe Kiland
Tonby, Kristian
Lind, Andreas
Dudman, Susanne Gjeruldsen
Henriksen, Katerina Nezvalova
Müller, Fredrik
Skjønsberg, Ole Henning
Trøseid, Marius
Barratt-Due, Andreas
Dyrhol-Riise, Anne Ma
Aukrust, Pål
Halvorsen, Bente
Dahl, Tuva Børresdatter
Ueland, Thor
author_facet Tveita, Anders
Murphy, Sarah Louise
Holter, Jan Cato
Kildal, Anders Benjamin
Michelsen, Annika E
Lerum, Tøri Vigeland
Kaarbø, Mari
Heggelund, Lars
Holten, Aleksander Rygh
Finbråten, Ane-Kristine
Müller, Karl Erik
Mathiessen, Alexander
Bøe, Simen
Fevang, Børre
Granerud, Beathe Kiland
Tonby, Kristian
Lind, Andreas
Dudman, Susanne Gjeruldsen
Henriksen, Katerina Nezvalova
Müller, Fredrik
Skjønsberg, Ole Henning
Trøseid, Marius
Barratt-Due, Andreas
Dyrhol-Riise, Anne Ma
Aukrust, Pål
Halvorsen, Bente
Dahl, Tuva Børresdatter
Ueland, Thor
author_sort Tveita, Anders
collection PubMed
description BACKGROUND: Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients. METHODS: Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms. RESULTS: A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up. CONCLUSIONS: Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19. CLINICAL TRIALS REGISTRATION: NCT04321616 and NCT04381819.
format Online
Article
Text
id pubmed-9384496
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-93844962022-08-18 High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19 Tveita, Anders Murphy, Sarah Louise Holter, Jan Cato Kildal, Anders Benjamin Michelsen, Annika E Lerum, Tøri Vigeland Kaarbø, Mari Heggelund, Lars Holten, Aleksander Rygh Finbråten, Ane-Kristine Müller, Karl Erik Mathiessen, Alexander Bøe, Simen Fevang, Børre Granerud, Beathe Kiland Tonby, Kristian Lind, Andreas Dudman, Susanne Gjeruldsen Henriksen, Katerina Nezvalova Müller, Fredrik Skjønsberg, Ole Henning Trøseid, Marius Barratt-Due, Andreas Dyrhol-Riise, Anne Ma Aukrust, Pål Halvorsen, Bente Dahl, Tuva Børresdatter Ueland, Thor J Infect Dis Major Article BACKGROUND: Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients. METHODS: Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms. RESULTS: A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up. CONCLUSIONS: Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19. CLINICAL TRIALS REGISTRATION: NCT04321616 and NCT04381819. Oxford University Press 2022-07-25 /pmc/articles/PMC9384496/ /pubmed/35876699 http://dx.doi.org/10.1093/infdis/jiac313 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Article
Tveita, Anders
Murphy, Sarah Louise
Holter, Jan Cato
Kildal, Anders Benjamin
Michelsen, Annika E
Lerum, Tøri Vigeland
Kaarbø, Mari
Heggelund, Lars
Holten, Aleksander Rygh
Finbråten, Ane-Kristine
Müller, Karl Erik
Mathiessen, Alexander
Bøe, Simen
Fevang, Børre
Granerud, Beathe Kiland
Tonby, Kristian
Lind, Andreas
Dudman, Susanne Gjeruldsen
Henriksen, Katerina Nezvalova
Müller, Fredrik
Skjønsberg, Ole Henning
Trøseid, Marius
Barratt-Due, Andreas
Dyrhol-Riise, Anne Ma
Aukrust, Pål
Halvorsen, Bente
Dahl, Tuva Børresdatter
Ueland, Thor
High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19
title High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19
title_full High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19
title_fullStr High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19
title_full_unstemmed High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19
title_short High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19
title_sort high circulating levels of the homeostatic chemokines ccl19 and ccl21 predict mortality and disease severity in covid-19
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384496/
https://www.ncbi.nlm.nih.gov/pubmed/35876699
http://dx.doi.org/10.1093/infdis/jiac313
work_keys_str_mv AT tveitaanders highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT murphysarahlouise highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT holterjancato highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT kildalandersbenjamin highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT michelsenannikae highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT lerumtørivigeland highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT kaarbømari highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT heggelundlars highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT holtenaleksanderrygh highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT finbratenanekristine highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT mullerkarlerik highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT mathiessenalexander highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT bøesimen highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT fevangbørre highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT granerudbeathekiland highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT tonbykristian highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT lindandreas highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT dudmansusannegjeruldsen highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT henriksenkaterinanezvalova highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT mullerfredrik highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT skjønsbergolehenning highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT trøseidmarius highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT barrattdueandreas highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT dyrholriiseannema highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT aukrustpal highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT halvorsenbente highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT dahltuvabørresdatter highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT uelandthor highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19
AT highcirculatinglevelsofthehomeostaticchemokinesccl19andccl21predictmortalityanddiseaseseverityincovid19