Severe COVID Alters Innate Immune System in Human, Animal Studies

On August 18, 2023, the National Institutes of Health (NIH) published a press release announcing a potential link between severe COVID-19 and changes to the innate immune system. The National Institute of Allergy and Infectious Diseases (NIAID) funded a study published in Cell, which revealed the conclusions.

The study looked at both human and animal immune systems. In the first component, the researchers assessed immune cells, molecules, and blood samples from 38 patients recovering from severe COVID-19. An additional 19 healthy patients were analyzed for comparison.

Rather than using a highly invasive bone marrow transplant to assess immune cells, researchers collected hematopoietic stem and progenitor cells (HSPCs) from enriched peripheral blood. They noted that it provided a good sample representative of bone marrow HSPCs.

Patients were evaluated for up to one year after severe infection. According to the study, patients with severe COVID-19 infections had distinct transcription factor activities, altered inflammatory regulation, and increased myelopoiesis.

The NIH press release notes, “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. The researchers observed these changes as much as a year after the participants came down with COVID-19.”

Although the data showed evidence of immune system changes, the researchers could not make definitive conclusions or validate associations due to the small participant pool. However, they theorized that IL-6, an inflammatory cytokine, may alter gene expression, impacting the innate immune system.

To assess their hypothesis, the investigators, including lead investigator Steven Z. Josefowicz, PhD, of Weill Cornell Medicine, used human participants and mouse models with COVID or COVID-like illness, respectively, to understand alterations in gene expression.

“In these experiments, some of the subjects received antibodies at the early stage of illness that prevented IL-6 from binding to cells. During recovery, these mice and people had lower levels of altered stem cell gene-expression instructions, monocyte production, and inflammatory cytokine production than subjects that didn’t receive the antibody. In addition, the lungs and brains of mice that received the antibodies had fewer monocyte-derived cells and less organ damage,” noted the press release.

While additional studies on these findings are required to assess the relationship further, the data implies that long-term inflammation in patients with severe COVID-19 is mediated by early IL-6 expression. The results also emphasize the importance of COVID vaccines to prevent severe illness.