tetano
Editor, Senior Moderator
Nat Med
. 2022 Dec 8.
doi: 10.1038/s41591-022-02107-4. Online ahead of print.
Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae
Ryan C Thompson[SUP] 1 2 [/SUP], Nicole W Simons[SUP] 3 [/SUP], Lillian Wilkins[SUP] 3 [/SUP], Esther Cheng[SUP] 3 [/SUP], Diane Marie Del Valle[SUP] 3 4 [/SUP], Gabriel E Hoffman[SUP] 5 [/SUP], Carlo Cervia[SUP] 6 [/SUP], Brian Fennessy[SUP] 3 [/SUP], Konstantinos Mouskas[SUP] 3 7 [/SUP], Nancy J Francoeur[SUP] 8 9 [/SUP], Jessica S Johnson[SUP] 3 [/SUP], Lauren Lepow[SUP] 3 [/SUP], Jessica Le Berichel[SUP] 3 4 [/SUP], Christie Chang[SUP] 3 4 10 [/SUP], Aviva G Beckmann[SUP] 11 [/SUP], Ying-Chih Wang[SUP] 8 9 [/SUP], Kai Nie[SUP] 10 [/SUP], Nicholas Zaki[SUP] 10 [/SUP], Kevin Tuballes[SUP] 4 [/SUP], Vanessa Barcessat[SUP] 4 [/SUP], Mario A Cedillo[SUP] 12 [/SUP], Dan Yuan[SUP] 13 14 [/SUP], Laura Huckins[SUP] 5 15 [/SUP], Panos Roussos[SUP] 8 15 16 17 18 19 20 [/SUP], Thomas U Marron[SUP] 1 3 4 21 22 23 [/SUP], Mount Sinai COVID-19 Biobank Team; Benjamin S Glicksberg[SUP] 1 24 [/SUP], Girish Nadkarni[SUP] 1 2 25 [/SUP], James R Heath[SUP] 13 14 [/SUP], Edgar Gonzalez-Kozlova[SUP] 3 21 [/SUP], Onur Boyman[SUP] 6 26 [/SUP], Seunghee Kim-Schulze[SUP] 3 4 10 21 27 [/SUP], Robert Sebra[SUP] 8 9 11 28 [/SUP], Miriam Merad[SUP] 3 4 27 [/SUP], Sacha Gnjatic[SUP] 3 4 10 21 23 27 [/SUP], Eric E Schadt[SUP] 8 11 [/SUP], Alexander W Charney[SUP] #[/SUP][SUP] 29 30 31 [/SUP], Noam D Beckmann[SUP] #[/SUP][SUP] 32 33 34 35 36 [/SUP]
Collaborators, Affiliations
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.
. 2022 Dec 8.
doi: 10.1038/s41591-022-02107-4. Online ahead of print.
Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae
Ryan C Thompson[SUP] 1 2 [/SUP], Nicole W Simons[SUP] 3 [/SUP], Lillian Wilkins[SUP] 3 [/SUP], Esther Cheng[SUP] 3 [/SUP], Diane Marie Del Valle[SUP] 3 4 [/SUP], Gabriel E Hoffman[SUP] 5 [/SUP], Carlo Cervia[SUP] 6 [/SUP], Brian Fennessy[SUP] 3 [/SUP], Konstantinos Mouskas[SUP] 3 7 [/SUP], Nancy J Francoeur[SUP] 8 9 [/SUP], Jessica S Johnson[SUP] 3 [/SUP], Lauren Lepow[SUP] 3 [/SUP], Jessica Le Berichel[SUP] 3 4 [/SUP], Christie Chang[SUP] 3 4 10 [/SUP], Aviva G Beckmann[SUP] 11 [/SUP], Ying-Chih Wang[SUP] 8 9 [/SUP], Kai Nie[SUP] 10 [/SUP], Nicholas Zaki[SUP] 10 [/SUP], Kevin Tuballes[SUP] 4 [/SUP], Vanessa Barcessat[SUP] 4 [/SUP], Mario A Cedillo[SUP] 12 [/SUP], Dan Yuan[SUP] 13 14 [/SUP], Laura Huckins[SUP] 5 15 [/SUP], Panos Roussos[SUP] 8 15 16 17 18 19 20 [/SUP], Thomas U Marron[SUP] 1 3 4 21 22 23 [/SUP], Mount Sinai COVID-19 Biobank Team; Benjamin S Glicksberg[SUP] 1 24 [/SUP], Girish Nadkarni[SUP] 1 2 25 [/SUP], James R Heath[SUP] 13 14 [/SUP], Edgar Gonzalez-Kozlova[SUP] 3 21 [/SUP], Onur Boyman[SUP] 6 26 [/SUP], Seunghee Kim-Schulze[SUP] 3 4 10 21 27 [/SUP], Robert Sebra[SUP] 8 9 11 28 [/SUP], Miriam Merad[SUP] 3 4 27 [/SUP], Sacha Gnjatic[SUP] 3 4 10 21 23 27 [/SUP], Eric E Schadt[SUP] 8 11 [/SUP], Alexander W Charney[SUP] #[/SUP][SUP] 29 30 31 [/SUP], Noam D Beckmann[SUP] #[/SUP][SUP] 32 33 34 35 36 [/SUP]
Collaborators, Affiliations
- PMID: 36482101
- DOI: 10.1038/s41591-022-02107-4
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.