A small study suggests that severe COVID-19 may cause long-term changes in the innate immune system, which is the first line of defense against pathogens. These changes may help explain why the disease damages so many different organs and why some people with long new crowns (LONG COVID) have high levels of systemic inflammation. The findings were published online Aug. 18, 2023, in the journal Cell under the title "Epigenetic memory of coronavirus infection in innate immune cells and their progenitors ".
Paper co-corresponding author Steven Z. Josefowicz, PhD, of Weill Cornell Medical College, and his team of researchers examined immune cells and molecules in blood samples from 38 patients with severe COVID-19 and other serious illnesses, as well as 19 healthy individuals. Notably, they established a new technique for collecting, concentrating, and characterizing the very rare hematopoietic stem cells that circulate in the bloodstream, thereby eliminating the need to extract these cells from the bone marrow.
In these rare stem cells taken from COVID-19 survivors, these authors found changes in the instructions that turn genes on or off. These changes were passed on to their daughter cells, causing them to promote the production of immune cells called monocytes. In the monocytes of people recovering from severe COVID-19, the changes in gene expression caused these cells to release more molecules called inflammatory cytokines than the monocytes of people who were healthy or did not have COVID-19.
These authors observed these changes one year after these participants were infected with SARS-CoV-2, the coronavirus that causes COVID-19. Because of the small number of people involved in the study, they were unable to determine a direct link between these cellular and molecular changes and health outcomes.
These authors hypothesized that an inflammatory cytokine called IL-6 might play a role in the changes in gene expression instructions. They tested this hypothesis in mice with COVID-19-like diseases and in patients with COVID-19.
In these experiments, some subjects were treated early in the disease with antibodies that prevented IL-6 from binding to cells. During recovery, these mice and patients had lower levels of altered hematopoietic stem cell gene expression directives, monocyte production, and inflammatory cytokine production than subjects who did not receive the antibody treatment. In addition, mice treated with these antibodies had lower numbers of monocytes in the lungs and brain and less organ damage.
Image from Cell, 2023, doi:10.1016/j.cell.2023.07.019.
These findings suggest that SARS-CoV-2 can lead to changes in gene expression that ultimately promote the production of inflammatory cytokines, and that one of these cytokines can induce these changes in hematopoietic stem cells even after the disease has ended, thereby perpetuating the process.
Furthermore, these findings suggest that early acting IL-6 may be a major driver of long-term inflammation in patients with severe COVID-19. These findings shed light on the pathogenesis of SARS-CoV-2 infection and may provide new clues for treatment. These findings also underscore the importance of timely vaccination with the recommended COVID-19 vaccines, which have been shown to prevent severe illness, hospitalization, and death.
