From the Journals

Severe COVID may cause long-term cellular changes: Study



Severe COVID infections may lead to lasting damage to the immune system, new research finds.

The small study, published in Cell and funded by the National Institutes of Health, details how immune cells were analyzed through blood samples collected from 38 patients recovering from severe COVID and other critical illnesses, and from 19 healthy people. Researchers from Weill Cornell Medicine, New York, and The Jackson Laboratory for Genomic Medicine, Farmington, Conn., found through isolating hematopoietic stem cells that people recovering from severe bouts of COVID had changes to their DNA that were passed down to offspring cells.

The research team, led by Steven Josefowicz, PhD, of Weill Cornell’s pathology department, and Duygu Ucar, PhD, associate professor at The Jackson Laboratory for Genomic Medicine, discovered that this chain reaction of stem cell changes caused a boost in the production of monocytes. The authors found that, due to the innate cellular changes from a severe case of COVID, patients in recovery ended up producing a larger amount of inflammatory cytokines, rather than monocytes – distinct from samples collected from healthy patients and those recovering from other critical illnesses.

These changes to patients’ epigenetic landscapes were observed even a year after the initial COVID-19 infection. While the small participant pool meant that the research team could not establish a direct line between these innate changes and any ensuing health outcomes, the research provides us with clues as to why patients continue to struggle with inflammation and long COVID symptoms well after they recover.

While the authors reiterate the study’s limitations and hesitate to make any clear-cut associations between the results and long-term health outcomes, Wolfgang Leitner, PhD, from the NIH’s National Institute of Allergy and Infectious Diseases, predicts that long COVID can, at least in part, be explained by the changes in innate immune responses.

“Ideally, the authors would have had cells from each patient before they got infected, as a comparator, to see what the epigenetic landscape was before COVID changed it,” said Dr. Leitner. “Clear links between the severity of COVID and genetics were discovered already early in the pandemic and this paper should prompt follow-up studies that link mutations in immune genes with the epigenetic changes described here.”

Dr. Leitner said he had some initial predictions about the long-term impact of COVID-19, but he had not anticipated some of what the study’s findings now show.

“Unlike in the case of, for example, influenza, where the lungs go into ‘repair mode’ after the infection has been resolved – which leaves people susceptible to secondary infections for up to several months – this study shows that after severe COVID, the immune system remains in ‘emergency mode’ and in a heightened state of inflammation,” said Dr. Leitner.

“That further aggravates the problem the initial strong inflammation causes: even higher risk of autoimmune disease, but also, cancer.”

Commenting on the findings, Eric Topol, MD, editor-in-chief of Medscape Medical News, said the study presents “evidence that a key line of immune cells are essentially irrevocably, epigenetically altered and activated.

“You do not want to have this [COVID],” he added.

The study also highlights the researchers’ novel approach to isolating hematopoietic stem cells, found largely in bone marrow. This type of research has been limited in the past because of how costly and invasive it can be to analyze cells in bone marrow. But, by isolating and enriching hematopoietic stem cells, the team can decipher the full cellular diversity of the cells’ bone marrow counterparts.

“This revelation opened the doors to study, at single-cell resolution, how stem cells are affected upon infection and vaccination with a simple blood draw,” representatives from the Jackson lab said in a press release.

A version of this article appeared on

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