Severe COVID-19 may cause long-lasting alterations to the innate immune system, the primary line of defense against pathogens, based on a small study funded by the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health. These changes may help explain why the disease can damage so many alternative organs and why some individuals with long COVID have high levels of inflammation throughout the body. The findings were published online today within the journal Cell.

Researchers led by Steven Z. Josefowicz, Ph.D., of Weill Cornell Medicine in Recent York City examined immune cells and molecules in blood samples from 38 people recovering from severe COVID-19 and other severe illnesses, in addition to from 19 healthy people. Notably, the researchers established a latest technique for collecting, concentrating and characterizing very rare blood-forming stem cells that flow into within the blood, eliminating the necessity to extract such cells from bone marrow.

In these rare stem cells-;the parents of immune-system cells-;taken from people recovering from COVID-19, the scientists identified changes within the instructions for which genes got turned on or off. These changes were passed right down to daughter cells, leading them to spice up production of immune cells called monocytes. Within the monocytes from people recovering from severe COVID-19, the changes in gene expression led the cells to pump out greater amounts of molecules called inflammatory cytokines than monocytes from individuals who were healthy or had non-COVID-19 illnesses. The researchers observed these changes as much as a 12 months after the participants got here down with COVID-19. Resulting from the small variety of study participants, the scientists couldn’t establish a direct association between the cellular and molecular changes and health outcomes.

The investigators suspected that an inflammatory cytokine called IL-6 might play role in establishing the changes in gene-expression instructions. They tested their hypothesis each in mice with COVID-19-like disease and in individuals with COVID-19. In these experiments, a number of the subjects received antibodies on the early stage of illness that prevented IL-6 from binding to cells. During recovery, these mice and folks had lower levels of altered stem cell gene-expression instructions, monocyte production and inflammatory cytokine production than subjects that did not receive the antibody. As well as, the lungs and brains of mice that received the antibodies had fewer monocyte-derived cells and fewer organ damage.

These findings suggest that SARS-CoV-2 may cause changes in gene expression that ultimately boost the production of inflammatory cytokines, and one form of those cytokines perpetuates the method by inducing these changes in stem cells even after the illness is over. Moreover, the findings suggest that early-acting IL-6 is probably going a serious driver of long-term inflammation in individuals with severe COVID-19. These findings make clear the pathogenesis of SARS-CoV-2 infection and will provide latest leads for therapies. The outcomes also underscore the importance of staying up to this point with really helpful COVID-19 vaccines, that are proven to guard against serious illness, hospitalization and death.

Source:

NIH/National Institute of Allergy and Infectious Diseases

Journal reference:

Cheong, J-G., et al. (2023) Epigenetic memory of coronavirus infection in innate immune cells and their progenitors. Cell. doi.org/10.1016/j.cell.2023.07.019.