Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system

The study “Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system” provides significant insights into the long-term effects of COVID-19 on the immune system.

Here’s a summary:

  1. Study Overview: The research by Cheong et al. focused on how COVID-19 causes interleukin-6 (IL-6) induced epigenetic reprogramming of human immune stem cells, leading to lasting alterations in the composition and response characteristics of circulating immune cells. This study is crucial in understanding the mechanisms of post-acute sequelae of COVID-19 (PASC), commonly referred to as long-COVID​​.
  2. Methodology and Findings:
    • Cheong et al. investigated changes in patients’ circulating immune cells after the clearance of acute SARS-CoV-2 infection, analyzing samples from COVID-19 convalescent patients and comparing them to non-infected controls. The focus was on peripheral blood mononuclear cells (PBMCs), particularly CD14+ monocytes, using transcriptome analysis and ATAC-seq sequencing.
    • CD14+ monocytes showed the most drastic changes, with one cluster, M.SC3, being more abundant even 12 months after infection. These cells resembled intermediate-type monocytes with enhanced antigen-presenting capabilities. Post-COVID monocytes exhibited up to a 100-fold increase in the secretion of proinflammatory cytokines and heightened transcriptional responses related to cytokine signaling and monocyte activation. Persistent epigenetic changes were observed in these cells, indicating a state of heightened alertness​​.
  3. Implications for Understanding Long COVID:
    • The discovery that IL-6 induces epigenetic reprogramming of immune cells, leading to persistent immune changes in post-COVID monocytes, is a critical step toward understanding the etiology of long COVID. These findings suggest the concept of ‘trained immunity’ or ‘innate immune memory,’ where the immune system retains a memory of past infections, leading to altered responses to subsequent challenges.
    • The study’s results also have implications for understanding the mechanism of anti-IL6R therapies, which are used in various diseases including rheumatoid arthritis and cytokine release syndrome associated with cancer therapies. The ability to reprogram hematopoietic stem and progenitor cells (HSPCs) into less debilitating epigenetic states could be crucial in preventing and treating the adverse consequences of an ill-trained innate immune system​​.

This research contributes significantly to the understanding of long COVID, particularly in the context of the immune system’s response to SARS-CoV-2 infection, and lays the groundwork for future studies and potential therapeutic strategies.

Read More: https://www.nature.com/articles/s41392-023-01717-9

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