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 - 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 - Bogunovic, Dusan
AU - Brown, Stacey Ann
AU - Chang, Serena
AU - Chien, Jonathan
AU - Comella, Phillip H.
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 - Gnjatic, Sacha
AU - Handler, Diana
AU - Harris, Jocelyn
AU - Humblin, Etienne
AU - Jordan, Daniel
AU - Kelly, Geoffrey
AU - Kumar, Arvind
AU - Lee, Brian
AU - Liharska, Lora E.
AU - Lindblad, Katherine
AU - Marvin, Robert
AU - Meckel, Katherine
AU - Mehandru, Saurabh
AU - Merad, Miriam
AU - Mollaoglu, Gurkan
AU - Nadkarni, Girish
AU - Onel, Kenan
AU - Patel, Manishkumar
AU - Rahman, Adeeb
AU - Redes, Jamie
AU - Reyes-Torres, Ivan
AU - Roudko, Vladimir
AU - Scott, Ieisha
AU - Sebra, Robert
AU - Tyler, Scott R.
AU - Van Der Heide, Verena
AU - Vaninov, Natalie
AU - Wacker, Daniel
AU - Wilson, Karen M.
AU - Xie, Hui
AU - Yu, Alex
AU - Zaks, Nina
AU - Glicksberg, Benjamin S.
AU - Kim-Schulze, Seunghee
AU - Schadt, Eric E.
AU - Charney, Alexander W.
N1 - Funding Information:
This manuscript is dedicated to study participants of the Mount Sinai COVID-19 Biobank and the healthcare workers who saved their lives. The Mount Sinai COVID-19 Biobank and the work performed here was supported by a redeployed workforce at the Icahn School of Medicine at Mount Sinai, supported by the following centers, programs, departments and institutes: Mount Sinai COVID-19 Informatics Center; Department of Genetics and Genomic Sciences; Human Immune Monitoring Center; Program for the Protection of Human Subjects; Department of Psychiatry; Department of Medicine; Department of Oncological Sciences; Department of Pediatrics; Precision Immunology Institute; Tisch Cancer Institute; Icahn Institute for Data Science and Genomic Technology; Friedman Brain Institute; Charles Bronfman Institute of Personalized Medicine; Hasso Plattner Institute for Digital Health; Mindich Child Health and Development Institute; and Black Family Stem Cell Institute. N. Herrera and S. C. Almo from the Albert Einstein College of Medicine provided the spike protein used in the ELISA measuring the anti-spike antibody titers. This work was supported, in part, through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. S.G., E.G.K, D.M.D.V. and M.M. were supported by National Cancer Institute U24 grant CA224319. S.G. is additionally supported by grants U01 DK124165 and U24 CA196521. C.C. and O.B. were supported by Swiss National Science Foundation grants, including NRP 78 Implementation Program, 4078P0-198431 and 310030-200669. D.Y. and J.R.H. were supported by the National Institute of Allergy and Infectious Diseases, award numbers 3R01AI141953-02S1 and 3R01AI141953-02S2.
Funding Information:
This manuscript is dedicated to study participants of the Mount Sinai COVID-19 Biobank and the healthcare workers who saved their lives. The Mount Sinai COVID-19 Biobank and the work performed here was supported by a redeployed workforce at the Icahn School of Medicine at Mount Sinai, supported by the following centers, programs, departments and institutes: Mount Sinai COVID-19 Informatics Center; Department of Genetics and Genomic Sciences; Human Immune Monitoring Center; Program for the Protection of Human Subjects; Department of Psychiatry; Department of Medicine; Department of Oncological Sciences; Department of Pediatrics; Precision Immunology Institute; Tisch Cancer Institute; Icahn Institute for Data Science and Genomic Technology; Friedman Brain Institute; Charles Bronfman Institute of Personalized Medicine; Hasso Plattner Institute for Digital Health; Mindich Child Health and Development Institute; and Black Family Stem Cell Institute. N. Herrera and S. C. Almo from the Albert Einstein College of Medicine provided the spike protein used in the ELISA measuring the anti-spike antibody titers. This work was supported, in part, through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. S.G., E.G.K, D.M.D.V. and M.M. were supported by National Cancer Institute U24 grant CA224319. S.G. is additionally supported by grants U01 DK124165 and U24 CA196521. C.C. and O.B. were supported by Swiss National Science Foundation grants, including NRP 78 Implementation Program, 4078P0-198431 and 310030-200669. D.Y. and J.R.H. were supported by the National Institute of Allergy and Infectious Diseases, award numbers 3R01AI141953-02S1 and 3R01AI141953-02S2.
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 -