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COVID-19 and trained immunity: the inflammatory burden of long covid

Jienan Gu1, Qianhui Liu2, Jiale Zhang1

  • 1Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Frontiers in Immunology
|December 13, 2023
PubMed

Insights

Severe COVID-19 causes lasting epigenetic changes in immune cells, potentially leading to chronic inflammation and related diseases through a process called trained immunity.

Area of Science:

  • Immunology
  • Epigenetics
  • Infectious Diseases

Background:

  • Severe COVID-19 triggers excessive inflammation driven by innate immune cells, particularly monocytes.
  • Epigenetic alterations, including increased chromatin accessibility in monocytes, persist post-recovery.
  • These changes suggest a reprogramming of hematopoietic stem and progenitor cells (HSPCs), indicative of trained immunity.

Purpose of the Study:

  • To investigate the epigenetic reprogramming of HSPCs and monocytes following severe COVID-19.
  • To understand the role of cytokines like IL-6 and IL-1β in mediating these epigenetic changes.
  • To explore the implications of persistent monocyte inflammation for long-term health outcomes and disease exacerbation.

Main Methods:

  • Analysis of epigenetic modifications in monocytes and HSPCs from patients recovering from severe COVID-19.
  • Quantification of inflammatory mediators, including IL-6 and IL-1β.
  • Assessment of chromatin accessibility at key immune-related genes.

Main Results:

  • Evidence of extensive epigenetic changes in monocytes during COVID-19 recovery, linked to cytokine production and leukocyte activation.
  • Identification of IL-6 as a key mediator in establishing durable epigenetic modifications in monocytes.
  • HSPC reprogramming appears to be the origin of persistent monocyte epigenetic memory.

Conclusions:

  • COVID-19-induced trained immunity in monocytes may contribute to chronic inflammation, tissue damage, and post-acute sequelae.
  • Hematopoietic epigenetic reprogramming by COVID-19 could exacerbate inflammatory diseases.
  • Further research is needed to elucidate mechanisms and develop interventions targeting IL-6 to mitigate sustained inflammation.

Keywords:
chronic inflammationhematopoietic stem and progenitor cellsinnate immuneinterleukin-1βinterleukin-6monocytespost-acute sequelae of COVID-19 symptoms

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