TY - JOUR
T1 - Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS
AU - COMET Consortium
AU - Sarma, Aartik
AU - Christenson, Stephanie A.
AU - Byrne, Ashley
AU - Mick, Eran
AU - Pisco, Angela Oliveira
AU - DeVoe, Catherine
AU - Deiss, Thomas
AU - Ghale, Rajani
AU - Zha, Beth Shoshana
AU - Tsitsiklis, Alexandra
AU - Jauregui, Alejandra
AU - Moazed, Farzad
AU - Detweiler, Angela M.
AU - Spottiswoode, Natasha
AU - Sinha, Pratik
AU - Neff, Norma
AU - Tan, Michelle
AU - Serpa, Paula Hayakawa
AU - Willmore, Andrew
AU - Ansel, K. Mark
AU - Wilson, Jennifer G.
AU - Leligdowicz, Aleksandra
AU - Siegel, Emily R.
AU - Sirota, Marina
AU - DeRisi, Joseph L.
AU - Matthay, Michael A.
AU - Abe-Jones, Yumiko
AU - Asthana, Saurabh
AU - Beagle, Alexander
AU - Bhakta, Tanvi
AU - Bhide, Sharvari
AU - Cai, Cathy
AU - Caldera, Saharai
AU - Calfee, Carolyn
AU - Calvo, Maria
AU - Carrillo, Sidney
AU - Cattamanchi, Adithya
AU - Chak, Suzanna
AU - Chan, Vincent
AU - Chew, Nayvin
AU - Christenson, Stephanie
AU - Collins, Zachary
AU - Combes, Alexis
AU - Courau, Tristan
AU - Darmanis, Spyros
AU - Erle, David
AU - Esmaili, Armond
AU - Fragiadakis, Gabriela K.
AU - Ghale, Rajani
AU - Liu, Yale
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a “cytokine storm,” we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.
AB - The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a “cytokine storm,” we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.
UR - https://www.scopus.com/pages/publications/85115173933
U2 - 10.1038/s41467-021-25040-5
DO - 10.1038/s41467-021-25040-5
M3 - 文章
C2 - 34446707
AN - SCOPUS:85115173933
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5152
ER -