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Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

2022; Nature Portfolio; Volume: 29; Issue: 1 Linguagem: Inglês

10.1038/s41591-022-02107-4

1546-170X

Ryan C. Thompson, Nicole W. Simons, Lillian Wilkins, Esther Cheng, Diane M. Del Valle, Gabriel E. Hoffman, Carlo Cervia, Brian Fennessy, Konstantinos Mouskas, Nancy Francoeur, Jessica Johnson, Lauren Lepow, Jessica Le Bérichel, Christie Chang, Aviva G. Beckmann, Ying‐Chih Wang, Kai Nie, Nicholas Zaki, Kevin Tuballes, Vanessa Barcessat, Mario A. Cedillo, Dan Yuan, Laura M. Huckins, Panos Roussos, Thomas U. Marron, Charuta Agashe, Priyal Agrawal, Alara Akyatan, Kasey Alesso-Carra, Eziwoma Alibo, Kelvin Alvarez, Angelo Amabile, Carmen Argmann, Kimberly Argueta, Steven Ascolillo, Rasheed Bailey, Craig Batchelor, Noam D. Beckmann, Priya Begani, Dusan Bogunovic, Swaroop Bose, Cansu Cimen Bozkus, Paloma Bravo, Stacey-Ann Whittaker Brown, Mark Buckup, Larissa Burka, Sharlene Calorossi, Lena Cambron, Guillermo Carbonell, Gina Carrara, Mario A. Cedillo, Christie Chang, Serena Chang, Steven T. Chen, Jonathan Chien, Mashkura Chowdhury, Jonathan Chung, Phillip Comella, Dana Cosgrove, Francesca Cossarini, Liam Cotter, Arpit Dave, Travis Dawson, Bheesham D. Dayal, Maxime Dhainaut, Rebecca Dornfeld, Katie Dul, Melody Eaton, Nissan Eber, Cordelia Elaiho, Ethan Ellis, Frank Fabris, Jeremiah J. Faith, Dominique Falci, Susie Feng, Marie Fernandes, Nataly Fishman, Nancy Francoeur, Sandeep Gangadharan, Daniel Geanon, Bruce D. Gelb, Benjamin S. Glicksberg, Sacha Gnjatic, Edgar Gonzalez‐Kozlova, Joanna Grabowska, Gavin Gyimesi, Maha Hamdani, Diana Handler, Jocelyn Harris, Matthew Hartnett, Sandra Hatem, Manon Herbinet, Elva Herrera, Arielle Hochman, Gabriel E. Hoffman, Jaime L. Hook, Laila Horta, Étienne Humblin, Suraj K. Jaladanki, Hajra Jamal, Daniel Jordan, Gurpawan Kang, Neha Karekar, Subha Karim, Geoffrey Kelly, Jong Kim, Seunghee Kim‐Schulze, Arvind Kumar, Jose Lacunza, Alona Lansky, Dannielle Lebovitch, Brian Lee, Grace Lee, Gyu Ho Lee, Jacky Lee, John Leech, Michael B. Leventhal, Lora E. Liharska, Katherine E. Lindblad, Alexandra E. Livanos, Rosalie Machado, Kent Madrid, Zafar Mahmood, Kelcey Mar, Thomas U. Marron, Glenn Martin, Robert Marvin, Shrisha Maskey, Paul D. Matthews, Katherine Meckel, Saurabh Mehandru, Miriam Mérad, Cynthia Mercedes, Elyze Merzier, Dara Meyer, Gürkan Mollaoglu, Sarah E. Morris, Konstantinos Mouskas, Emily Moya, Girish N. Nadkarni, Kai Nie, Marjorie Nisenholtz, George Ofori‐Amanfo, Kenan Onel, Merouane Ounadjela, Manishkumar Patel, Vishwendra Patel, Cassandra Pruitt, Adeeb Rahman, Shivani Rathi, Jamie Redes, Ivan Reyes-Torres, Alcina A. Rodrigues, Alfonso R. Sánchez-Paulete, Vladimir Roudko, Panos Roussos, E. de Celis Ruiz, Pearl Scalzo, Eric E. Schadt, Ieisha Scott, Robert Sebra, Sandra Serrano, Hardik Shah, Mark Shervey, Pedro Silva, Laura Sloofman, Melissa Smith, Alessandra Soares‐Schanoski, Juan Soto, Shwetha Hara Sridhar, Hiyab Stefanos, Meghan Straw, Robert E. Sweeney, Alexandra Tabachnikova, Collin D. Teague, Manying Tin, Kevin Tuballes, Scott R. Tyler, Bhaskar Upadhyaya, Akhil Vaid, Verena van der Heide, Natalie Vaninov, Konstantinos Vlachos, Daniel Wacker, Laura Walker, Hadley Walsh, Bo Wang, Wenhui Wang, Ying‐Chih Wang, C. Matthias Wilk, Jessica Wilson, Karen M. Wilson, Hui Xie, Xue Li, Naa-akomaah Yeboah, Nancy Yi, Mahlet Yishak, Sabina Young, Alex W. Yu, Nicholas Zaki, Nina Zaks, Renyuan Zha, Benjamin S. Glicksberg, Girish N. Nadkarni, James R. Heath, Edgar Gonzalez‐Kozlova, Onur Boyman, Seunghee Kim‐Schulze, Robert Sebra, Miriam Mérad, Sacha Gnjatic, Eric E. Schadt, Alexander W. Charney, Noam D. Beckmann,

COVID-19 and Mental Health

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.