학술논문
Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae
Document Type
Original Paper
Author
Thompson, Ryan C.; Simons, Nicole W.; Wilkins, Lillian; Cheng, Esther; Del Valle, Diane Marie; Hoffman, Gabriel E.; Cervia, Carlo; Fennessy, Brian; Mouskas, Konstantinos; Francoeur, Nancy J.; Johnson, Jessica S.; Lepow, Lauren; Le Berichel, Jessica; Chang, Christie; Beckmann, Aviva G.; Wang, Ying-chih; Nie, Kai; Zaki, Nicholas; Tuballes, Kevin; Barcessat, Vanessa; Cedillo, Mario A.; Yuan, Dan; Huckins, Laura; Roussos, Panos; Marron, Thomas U.; Glicksberg, Benjamin S.; Nadkarni, Girish; Heath, James R.; Gonzalez-Kozlova, Edgar; Boyman, Onur; Kim-Schulze, Seunghee; Sebra, Robert; Merad, Miriam; Gnjatic, Sacha; Schadt, Eric E.; Charney, Alexander W.; Beckmann, Noam D.
Source
Nature Medicine. 29(1):236-246
Subject
Language
English
ISSN
1078-8956
1546-170X
1546-170X
Abstract
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.
Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.
Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.