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Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19.
Liu, Zhaoli; Kilic, Gizem; Li, Wenchao; Bulut, Ozlem; Gupta, Manoj Kumar; Zhang, Bowen; Qi, Cancan; Peng, He; Tsay, Hsin-Chieh; Soon, Chai Fen; Mekonnen, Yonatan Ayalew; Ferreira, Anaísa Valido; van der Made, Caspar I; van Cranenbroek, Bram; Koenen, Hans J P M; Simonetti, Elles; Diavatopoulos, Dimitri; de Jonge, Marien I; Müller, Lisa; Schaal, Heiner; Ostermann, Philipp N; Cornberg, Markus; Eiz-Vesper, Britta; van de Veerdonk, Frank; van Crevel, Reinout; Joosten, Leo A B; Domínguez-Andrés, Jorge; Xu, Cheng-Jian; Netea, Mihai G; Li, Yang.
  • Liu Z; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Kilic G; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Li W; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Bulut O; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Gupta MK; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Zhang B; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Qi C; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Peng H; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Tsay HC; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Soon CF; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Mekonnen YA; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Ferreira AV; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • van der Made CI; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • van Cranenbroek B; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Koenen HJPM; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Simonetti E; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Diavatopoulos D; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • de Jonge MI; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Müller L; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Schaal H; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
  • Ostermann PN; TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Cornberg M; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Eiz-Vesper B; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
  • van de Veerdonk F; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • van Crevel R; Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands.
  • Joosten LAB; Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands.
  • Domínguez-Andrés J; Laboratory of Pediatric Infectious Diseases, Radboud Centre for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Xu CJ; Laboratory of Pediatric Infectious Diseases, Radboud Centre for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Netea MG; Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands.
  • Li Y; Institute of Virology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf, Germany.
Front Immunol ; 13: 838132, 2022.
Article in English | MEDLINE | ID: covidwho-1809394
ABSTRACT
The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in 14 convalescent COVID-19 and 15 healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays minor changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1Ra and IFN-γ was higher in convalescent individuals. In conclusion, we propose that despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Topics: Long Covid Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.838132

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Topics: Long Covid Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.838132