Cargando…

Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19

Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cel...

Descripción completa

Detalles Bibliográficos
Autores principales: Tsitsiklis, Alexandra, Zha, Beth Shoshana, Byrne, Ashley, Devoe, Catherine, Levan, Sophia, Rackaityte, Elze, Sunshine, Sara, Mick, Eran, Ghale, Rajani, Jauregui, Alejandra, Sarma, Aartik, Neff, Norma, Serpa, Paula Hayakawa, Deiss, Thomas J., Kistler, Amy, Carrillo, Sidney, Ansel, K. Mark, Leligdowicz, Aleksandra, Christenson, Stephanie, Jones, Norman, Wu, Bing, Darmanis, Spyros, Matthay, Michael A., Lynch, Susan V., DeRisi, Joseph L., Hendrickson, Carolyn M., Kangelaris, Kirsten N., Krummel, Matthew F., Woodruff, Prescott G., Erle, David J., Rosenberg, Oren, Calfee, Carolyn S., Langelier, Charles R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132240/
https://www.ncbi.nlm.nih.gov/pubmed/34013247
http://dx.doi.org/10.21203/rs.3.rs-380803/v1
_version_ 1783694876943056896
author Tsitsiklis, Alexandra
Zha, Beth Shoshana
Byrne, Ashley
Devoe, Catherine
Levan, Sophia
Rackaityte, Elze
Sunshine, Sara
Mick, Eran
Ghale, Rajani
Jauregui, Alejandra
Sarma, Aartik
Neff, Norma
Serpa, Paula Hayakawa
Deiss, Thomas J.
Kistler, Amy
Carrillo, Sidney
Ansel, K. Mark
Leligdowicz, Aleksandra
Christenson, Stephanie
Jones, Norman
Wu, Bing
Darmanis, Spyros
Matthay, Michael A.
Lynch, Susan V.
DeRisi, Joseph L.
Hendrickson, Carolyn M.
Kangelaris, Kirsten N.
Krummel, Matthew F.
Woodruff, Prescott G.
Erle, David J.
Rosenberg, Oren
Calfee, Carolyn S.
Langelier, Charles R.
author_facet Tsitsiklis, Alexandra
Zha, Beth Shoshana
Byrne, Ashley
Devoe, Catherine
Levan, Sophia
Rackaityte, Elze
Sunshine, Sara
Mick, Eran
Ghale, Rajani
Jauregui, Alejandra
Sarma, Aartik
Neff, Norma
Serpa, Paula Hayakawa
Deiss, Thomas J.
Kistler, Amy
Carrillo, Sidney
Ansel, K. Mark
Leligdowicz, Aleksandra
Christenson, Stephanie
Jones, Norman
Wu, Bing
Darmanis, Spyros
Matthay, Michael A.
Lynch, Susan V.
DeRisi, Joseph L.
Hendrickson, Carolyn M.
Kangelaris, Kirsten N.
Krummel, Matthew F.
Woodruff, Prescott G.
Erle, David J.
Rosenberg, Oren
Calfee, Carolyn S.
Langelier, Charles R.
author_sort Tsitsiklis, Alexandra
collection PubMed
description Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cell RNA sequencing (scRNA-seq) we assessed lower respiratory tract immune responses and microbiome dynamics in 28 COVID-19 patients, 15 of whom developed VAP, and eight critically ill uninfected controls. Two days before VAP onset we observed a transcriptional signature of bacterial infection. Two weeks prior to VAP onset, following intubation, we observed a striking impairment in immune signaling in COVID-19 patients who developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients with VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. These findings suggest that COVID-19 patients who develop VAP have impaired antibacterial immune defense detectable weeks before secondary infection onset.
format Online
Article
Text
id pubmed-8132240
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Journal Experts
record_format MEDLINE/PubMed
spelling pubmed-81322402021-05-20 Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19 Tsitsiklis, Alexandra Zha, Beth Shoshana Byrne, Ashley Devoe, Catherine Levan, Sophia Rackaityte, Elze Sunshine, Sara Mick, Eran Ghale, Rajani Jauregui, Alejandra Sarma, Aartik Neff, Norma Serpa, Paula Hayakawa Deiss, Thomas J. Kistler, Amy Carrillo, Sidney Ansel, K. Mark Leligdowicz, Aleksandra Christenson, Stephanie Jones, Norman Wu, Bing Darmanis, Spyros Matthay, Michael A. Lynch, Susan V. DeRisi, Joseph L. Hendrickson, Carolyn M. Kangelaris, Kirsten N. Krummel, Matthew F. Woodruff, Prescott G. Erle, David J. Rosenberg, Oren Calfee, Carolyn S. Langelier, Charles R. Res Sq Article Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cell RNA sequencing (scRNA-seq) we assessed lower respiratory tract immune responses and microbiome dynamics in 28 COVID-19 patients, 15 of whom developed VAP, and eight critically ill uninfected controls. Two days before VAP onset we observed a transcriptional signature of bacterial infection. Two weeks prior to VAP onset, following intubation, we observed a striking impairment in immune signaling in COVID-19 patients who developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients with VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. These findings suggest that COVID-19 patients who develop VAP have impaired antibacterial immune defense detectable weeks before secondary infection onset. American Journal Experts 2021-04-23 /pmc/articles/PMC8132240/ /pubmed/34013247 http://dx.doi.org/10.21203/rs.3.rs-380803/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Tsitsiklis, Alexandra
Zha, Beth Shoshana
Byrne, Ashley
Devoe, Catherine
Levan, Sophia
Rackaityte, Elze
Sunshine, Sara
Mick, Eran
Ghale, Rajani
Jauregui, Alejandra
Sarma, Aartik
Neff, Norma
Serpa, Paula Hayakawa
Deiss, Thomas J.
Kistler, Amy
Carrillo, Sidney
Ansel, K. Mark
Leligdowicz, Aleksandra
Christenson, Stephanie
Jones, Norman
Wu, Bing
Darmanis, Spyros
Matthay, Michael A.
Lynch, Susan V.
DeRisi, Joseph L.
Hendrickson, Carolyn M.
Kangelaris, Kirsten N.
Krummel, Matthew F.
Woodruff, Prescott G.
Erle, David J.
Rosenberg, Oren
Calfee, Carolyn S.
Langelier, Charles R.
Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
title Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
title_full Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
title_fullStr Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
title_full_unstemmed Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
title_short Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
title_sort impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132240/
https://www.ncbi.nlm.nih.gov/pubmed/34013247
http://dx.doi.org/10.21203/rs.3.rs-380803/v1
work_keys_str_mv AT tsitsiklisalexandra impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT zhabethshoshana impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT byrneashley impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT devoecatherine impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT levansophia impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT rackaityteelze impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT sunshinesara impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT mickeran impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT ghalerajani impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT jaureguialejandra impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT sarmaaartik impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT neffnorma impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT serpapaulahayakawa impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT deissthomasj impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT kistleramy impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT carrillosidney impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT anselkmark impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT leligdowiczaleksandra impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT christensonstephanie impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT jonesnorman impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT wubing impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT darmanisspyros impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT matthaymichaela impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT lynchsusanv impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT derisijosephl impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT hendricksoncarolynm impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT kangelariskirstenn impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT krummelmatthewf impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT woodruffprescottg impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT erledavidj impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT rosenbergoren impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT calfeecarolyns impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19
AT langeliercharlesr impairedimmunesignalingandchangesinthelungmicrobiomeprecedesecondarybacterialpneumoniaincovid19