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A small study backed by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, suggests that severe COVID-19 might induce prolonged alterations to the innate immune system, the body's primary defense against infections. These changes could partially explain the disease's capacity to impact various organs and the heightened systemic inflammation observed in some COVID patients. The findings were published online today in the journal Cell.
Researchers from Weill Cornell Medicine in New York City, led by Steven Z. Josefowicz, Ph.D., analyzed immune cells and chemicals in blood samples from 38 patients recovering from severe COVID-19 and other serious illnesses, as well as 19 healthy individuals. Importantly, the researchers introduced a novel method that avoids the need for bone marrow cell extraction, enabling the collection, concentration, and characterization of the rare blood-forming stem cells found in the bloodstream.
These scientists noted changes in the instructions determining which genes were active or inactive in these unique stem cells, derived from individuals recovering from COVID-19. These changes persisted in the daughter cells, elevating the number of immune cells, specifically monocytes. These altered gene expressions caused monocytes from patients recovering from severe COVID-19 to produce higher amounts of inflammatory cytokines compared to those from healthy subjects or those with non-COVID-19 diseases. These changes were observable up to a year post-COVID-19 diagnosis. However, due to the study's limited size, the researchers couldn't establish a direct link between these cellular and molecular changes.
The team theorized that IL-6, an inflammatory cytokine, might be responsible for the altered gene expressions. They tested this hypothesis in both mice mimicking a COVID-19-like condition and human COVID-19 patients. Some subjects in these experiments were administered antibodies early in the disease progression, blocking IL-6 from binding to cells. These mice and humans exhibited slower recovery compared to those not given the antibody, as they had reduced altered stem cell gene expressions, monocyte proliferation, and inflammatory cytokine production. Furthermore, mice treated with these antibodies presented fewer monocyte-derived cells and decreased organ damage in their lungs and brains.
Based on these findings, SARS-CoV-2 appears to modify gene expression, augmenting the secretion of inflammatory cytokines. A particular subtype of these cytokines perpetuates this effect by instigating changes in stem cells even after the infection has subsided. Moreover, the data indicate that early exposure to IL-6 might play a crucial role in persistent inflammation in individuals with severe COVID-19. These insights offer potential therapeutic avenues and elucidate the pathogenesis of the SARS-CoV-2 infection. The results underscore the importance of adhering to recommended COVID-19 vaccination schedules, proven to protect against severe disease, hospitalization, and mortality.