In a groundbreaking study by Weill Cornell Medicine and The Jackson Laboratory, researchers have unveiled compelling insights into the enduring effects of severe COVID-19 on the body's immune system. The findings shed light on the alterations in gene expression within immune system stem cells, offering a potential explanation for persistent inflammation and the emergence of long COVID symptoms.

Led by Steven Josefowicz, Ph.D., from Weill Cornell Medicine, and Duygu Ucar, Ph.D., from The Jackson Laboratory for Genomic Medicine, the research, published on August 18 in Cell, introduces a novel technique. This method isolates and analyzes rare CD34+ hematopoietic stem and progenitor cells from human blood, unraveling the intricacies of the epigenetic landscape — the packaging and condensation of DNA.

Epigenetic Footprints: Unveiling the Secrets of Stem Cells

The team examined stem cells from individuals who had recovered from severe COVID-19, investigating changes in the epigenetic landscape that dictate gene activation. Their groundbreaking discovery revealed that stem cells from COVID-19 survivors exhibited heightened accessibility of DNA, particularly at genes associated with inflammation and the determination of cell types. Importantly, these alterations extended to the mature immune cells derived from these stem cells, sensitizing them to future encounters with pathogens.

Josefowicz highlights the significance, stating, "We found that these stem cells can pass their epigenetic 'memories' on to their progeny immune cells, changing those cells' inflammatory programs."

While the adaptive immune system's memory of past infections is well-documented, the study delves into the less-explored realm of innate immune cells. These cells, the first responders to infection, undergo epigenetic changes in hematopoietic stem cells, influencing their responses to future threats.

A Breakthrough Approach to Studying Hematopoietic Stem Cells

Historically, studying hematopoietic stem cells, abundant in bone marrow, has been challenging due to invasive techniques. The team's innovative approach, focusing on stem cells circulating in the blood, provides a groundbreaking platform for investigating these cells at single-cell resolution. This newfound accessibility enables researchers to examine how stem cells respond to infection and vaccination through a simple blood draw.

The researchers, including first author Jin-Gyu Cheong, Ph.D., observed that epigenetic changes persisted in stem cells long after recovery from severe COVID-19. This discovery challenges conventional wisdom and suggests that the impact of the virus extends beyond the acute phase.

Beyond Stem Cells: Unraveling Immune Responses

Expanding their investigation beyond stem cells, the team examined monocytes, white blood cells crucial to the innate immune response. Remarkably, these cells exhibited altered epigenetic programming up to a year after severe COVID-19, making them hyper-responsive to stimulation.

Ucar emphasizes the broader implications, stating, "Understanding epigenetic memory associated with infections can be a way for us to understand how certain diseases like COVID-19 have such long-lasting health consequences."

Additionally, the researchers explored factors influencing the degree of epigenetic changes in patients. Notably, individuals treated with IL6 blockers during acute disease were less likely to experience significant immune memory changes a year later. The ongoing focus on understanding how inflammatory molecules and other factors shape lasting changes in stem cells remains at the forefront of their research.

Looking Ahead: Game-Changing Blood Stem Cell Research

Armed with this newfound platform, the researchers are poised to explore hematopoietic stem cell sub-types more accessible in the blood than bone marrow. Josefowicz declares, "With this workflow to study the plasticity of blood stem cells from a simple blood draw, it's now game on."

This groundbreaking study opens doors to unraveling the complexities of COVID-19's impact on the immune system, paving the way for future insights into diseases and therapies.

Key Takeaways:

• Severe COVID-19 induces lasting alterations in the immune system's gene expression.
• Stem cells from COVID-19 survivors exhibit heightened epigenetic changes, influencing immune responses.
• The study introduces an innovative technique to study hematopoietic stem cells with a simple blood draw.
• Epigenetic changes persist in stem cells and immune cells long after recovery from severe COVID-19.
• Understanding these epigenetic memories may provide insights into the long-term consequences of diseases like COVID-19.