Researchers Assess Innate Immune System Changes Following Severe COVID-19


Changes in gene expression could ultimately boost the production of inflammatory cytokines.

In a new study published in the journal Cell, researchers found that severe COVID-19 could trigger long-lasting alterations to the innate immune symptom, which is the initial defense against pathogens. The results of this study could explain why COVID-19 could cause damage to organs, along with why individuals that were diagnosed with long COVID displayed high levels of inflammation in the body.2

Cytokines - Image credit: 7activestudio |

Image credit: 7activestudio |

Following infection with COVID-19, individuals are at risk for long-term complications. Innate immune cell activation, combined with a delayed adaptive immune and interferon response, are often displayed in acute severe COVID-19. However, changes that take place within the immune system could impact future responses to pathogens and vaccines that connect to long-term clinical symptoms.1

The study was led by Steven Z. Josefowicz, PhD., of Weill Cornell Medicine in New York City. Josefowicz and researchers included 38 individuals that were recovering from severe COVID-19 and other severe illnesses, and 19 healthy individuals in the study. The study authors noted that the researchers examined immune cells and molecules in blood samples from both groups of individuals.2

Rather than extracting cells from bone marrow, the study authors created a new technique for collecting that involved “concentrating and characterizing very rare blood-forming stem cells that circulate in the blood.”1

The researchers took rare stem cells from the individuals that were recovering from COVID-19, which were the parents of the immune-system cells. The researchers then were able to pinpoint the changes in the guide for the certain genes that were turned on or off.2

“These changes were passed down to daughter cells, leading them to boost production of immune cells called monocytes. In 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 people who were healthy or had non-COVID-19 illnesses,” said the study authors.

The participants with COVID-19 were monitored for a year to observe the reported changes. However, the study authors noted that because the study was small, the researchers were not able to connect the cellular and molecular changes, as well as the health outcomes.2

The researchers used mice that had similar diseases to COVID-19 and individuals with COVID-19 to test whether an inflammatory cytokine, interleukin (IL)-6, contributed to the changes in the gene-expression method.2

The study authors noted the subjects that received antibodies at earlier phases of the illness displayed prevention of IL-6 binding to cells. When the individuals and mice were in recovery from the illness they presented lower levels of altered stem cell gene-expression instructions, monocyte production, and inflammatory cytokine production, compared to subjects that did not receive the antibody.2

“These findings suggest that SARS-CoV-2 can cause changes in gene expression that ultimately boost the production of inflammatory cytokines, and one type of those cytokines perpetuates the process by inducing these changes in stem cells even after the illness is over,” said the study authors.

The press release noted that the results found that IL-6 contributes to long-term inflammation in individuals with severe COVID-19. However, the researchers highlight and recommend for individuals to receive each COVID-19 vaccine to be protected against the illness.2


  1. Epigenetic memory of coronavirus infection in innate immune cells and their progenitors. Cell. News release. August 31, 2023. Accessed November 6, 2023.
  2. Severe COVID-19 may lead to long-term innate immune system changes. EurekAlert!. News release. August 18, 2023. Accessed November 6, 2023.
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