tetano
Editor, Senior Moderator
Genome Med
. 2023 Sep 12;15(1):69.
doi: 10.1186/s13073-023-01227-x. SARS-CoV-2 infection induces a long-lived pro-inflammatory transcriptional profile
Jia-Yuan Zhang[SUP] 1 [/SUP], Justin P Whalley[SUP] 2 3 [/SUP], Julian C Knight[SUP] 2 4 [/SUP], Linda S Wicker[SUP] #[/SUP][SUP] 1 [/SUP], John A Todd[SUP] #[/SUP][SUP] 5 [/SUP], Ricardo C Ferreira[SUP] #[/SUP][SUP] 6 [/SUP]
Affiliations
Background: The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in COVID-19 patients has been extensively investigated. However, much less is known about the long-term effects of infection in patients and how it could affect the immune system and its capacity to respond to future perturbations.
Methods: Using a targeted single-cell multiomics approach, we have recently identified a prolonged anti-inflammatory gene expression signature in T and NK cells in type 1 diabetes patients treated with low-dose IL-2. Here, we investigated the dynamics of this signature in three independent cohorts of COVID-19 patients: (i) the Oxford COVID-19 Multi-omics Blood Atlas (COMBAT) dataset, a cross-sectional cohort including 77 COVID-19 patients and ten healthy donors; (ii) the INCOV dataset, consisting of 525 samples taken from 209 COVID-19 patients during and after infection; and (iii) a longitudinal dataset consisting of 269 whole-blood samples taken from 139 COVID-19 patients followed for a period of up to 7 months after the onset of symptoms using a bulk transcriptomic approach.
Results: We discovered that SARS-CoV-2 infection leads to a prolonged alteration of the gene expression profile of circulating T, B and NK cells and monocytes. Some of the genes affected were the same as those present in the IL-2-induced anti-inflammatory gene expression signature but were regulated in the opposite direction, implying a pro-inflammatory status. The altered transcriptional profile was detected in COVID-19 patients for at least 2 months after the onset of the disease symptoms but was not observed in response to influenza infection or sepsis. Gene network analysis suggested a central role for the transcriptional factor NF-κB in the regulation of the observed transcriptional alterations.
Conclusions: SARS-CoV-2 infection causes a prolonged increase in the pro-inflammatory transcriptional status that could predispose post-acute patients to the development of long-term health consequences, including autoimmune disease, reactivation of other viruses and disruption of the host immune system-microbiome ecosystem.
Keywords: COVID-19; IL-2-induced anti-inflammatory signature; NF-kB; Post-acute sequelae of COVID-19 (PASC); SARS-CoV-2; Single-cell multiomics.
. 2023 Sep 12;15(1):69.
doi: 10.1186/s13073-023-01227-x. SARS-CoV-2 infection induces a long-lived pro-inflammatory transcriptional profile
Jia-Yuan Zhang[SUP] 1 [/SUP], Justin P Whalley[SUP] 2 3 [/SUP], Julian C Knight[SUP] 2 4 [/SUP], Linda S Wicker[SUP] #[/SUP][SUP] 1 [/SUP], John A Todd[SUP] #[/SUP][SUP] 5 [/SUP], Ricardo C Ferreira[SUP] #[/SUP][SUP] 6 [/SUP]
Affiliations
- PMID: 37700317
- DOI: 10.1186/s13073-023-01227-x
Background: The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in COVID-19 patients has been extensively investigated. However, much less is known about the long-term effects of infection in patients and how it could affect the immune system and its capacity to respond to future perturbations.
Methods: Using a targeted single-cell multiomics approach, we have recently identified a prolonged anti-inflammatory gene expression signature in T and NK cells in type 1 diabetes patients treated with low-dose IL-2. Here, we investigated the dynamics of this signature in three independent cohorts of COVID-19 patients: (i) the Oxford COVID-19 Multi-omics Blood Atlas (COMBAT) dataset, a cross-sectional cohort including 77 COVID-19 patients and ten healthy donors; (ii) the INCOV dataset, consisting of 525 samples taken from 209 COVID-19 patients during and after infection; and (iii) a longitudinal dataset consisting of 269 whole-blood samples taken from 139 COVID-19 patients followed for a period of up to 7 months after the onset of symptoms using a bulk transcriptomic approach.
Results: We discovered that SARS-CoV-2 infection leads to a prolonged alteration of the gene expression profile of circulating T, B and NK cells and monocytes. Some of the genes affected were the same as those present in the IL-2-induced anti-inflammatory gene expression signature but were regulated in the opposite direction, implying a pro-inflammatory status. The altered transcriptional profile was detected in COVID-19 patients for at least 2 months after the onset of the disease symptoms but was not observed in response to influenza infection or sepsis. Gene network analysis suggested a central role for the transcriptional factor NF-κB in the regulation of the observed transcriptional alterations.
Conclusions: SARS-CoV-2 infection causes a prolonged increase in the pro-inflammatory transcriptional status that could predispose post-acute patients to the development of long-term health consequences, including autoimmune disease, reactivation of other viruses and disruption of the host immune system-microbiome ecosystem.
Keywords: COVID-19; IL-2-induced anti-inflammatory signature; NF-kB; Post-acute sequelae of COVID-19 (PASC); SARS-CoV-2; Single-cell multiomics.