TY - JOUR
T1 - Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae
AU - The Mount Sinai COVID-19 Biobank Team
AU - Thompson, Ryan C.
AU - Hoffman, Gabriel E.
AU - Johnson, Jessica S.
AU - Lepow, Lauren
AU - Nie, Kai
AU - Huckins, Laura
AU - Roussos, Panos
AU - Marron, Thomas U.
AU - Agashe, Charuta
AU - Argmann, Carmen
AU - Argueta, Kimberly
AU - Beckmann, Noam D.
AU - Begani, Priya
AU - Bogunovic, Dusan
AU - Cimen Bozkus, Cansu
AU - Brown, Stacey Ann
AU - Carbonell, Guillermo
AU - Chang, Serena
AU - Comella, Phillip H.
AU - Cossarini, Francesca
AU - Cotter, Liam
AU - Dave, Arpit
AU - Dawson, Travis
AU - Dayal, Bheesham
AU - Dhainaut, Maxime
AU - Faith, Jeremiah
AU - Gangadharan, Sandeep
AU - Gelb, Bruce D.
AU - Glicksberg, Benjamin S.
AU - Gnjatic, Sacha
AU - Gonzalez-Kozlova, Edgar
AU - Handler, Diana
AU - Harris, Jocelyn
AU - Hoffman, Gabriel E.
AU - Hook, Jaime
AU - Horta, Laila
AU - Humblin, Etienne
AU - Jordan, Daniel
AU - Kelly, Geoffrey
AU - Kim-Schulze, Seunghee
AU - Kumar, Arvind
AU - Lee, Brian
AU - Liharska, Lora E.
AU - Lindblad, Katherine
AU - Mahmood, Zafar
AU - Marron, Thomas U.
AU - Marvin, Robert
AU - Meckel, Katherine
AU - Mehandru, Saurabh
AU - Merad, Miriam
AU - Mollaoglu, Gurkan
AU - Nadkarni, Girish
AU - Nie, Kai
AU - Onel, Kenan
AU - Patel, Manishkumar
AU - Rahman, Adeeb
AU - Redes, Jamie
AU - Reyes-Torres, Ivan
AU - Rodriguez, Alfonso
AU - Roudko, Vladimir
AU - Roussos, Panos
AU - Schadt, Eric E.
AU - Scott, Ieisha
AU - Sebra, Robert
AU - Tyler, Scott R.
AU - Van Der Heide, Verena
AU - Vaninov, Natalie
AU - Wacker, Daniel
AU - Wilk, C. Matthias
AU - Wilson, Karen M.
AU - Xie, Hui
AU - Zaks, Nina
AU - Glicksberg, Benjamin S.
AU - Nadkarni, Girish
AU - Gonzalez-Kozlova, Edgar
AU - Kim-Schulze, Seunghee
AU - Sebra, Robert
AU - Charney, Alexander W.
AU - Beckmann, Noam D.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.
AB - Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.
UR - http://www.scopus.com/inward/record.url?scp=85143592766&partnerID=8YFLogxK
U2 - 10.1038/s41591-022-02107-4
DO - 10.1038/s41591-022-02107-4
M3 - Article
C2 - 36482101
AN - SCOPUS:85143592766
SN - 1078-8956
VL - 29
SP - 236
EP - 246
JO - Nature Medicine
JF - Nature Medicine
IS - 1
ER -