Image description: Image shows an inflammatory response to a blood cell. Inset pictures show a patient lying in bed with ME/CFS and a biochemist carrying out research. The title reads: Overactive inflammatory response could be at the root of many long COVID cases. The ME Association logo (bottom right)

Overactive inflammatory response in Long Covid

ME Association Comment

“The new ME Association guide to the links between Long Covid and ME/CFS explains that there are a number of possible explanations as to what is causing Long Covid – most of which apply to ME/CFS as well.

“One of the more promising lines of research relates to the possibility that the immune response that is triggered by the initial COVID-19 infection fails to switch off and a state of low level immune system activation persists – which again appears to be the case in ME/CFS.

“This new research, using more sophisticated markers of immune system activation, adds further support to this immune activation hypothesis and the way in which this could then be causing inflammation in various parts of the body.

“These findings also provide a good basis for assessing the use of drugs that can help to dampen down inflammation and immune system activation in both Long Covid and ME/CFS.”

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.

Dr Charles Shepherd

Article Extracts

Reviewed by Danielle Ellis, Medicalnet

An overactive inflammatory response could be at the root of many long COVID cases, according to a new study from the Allen Institute and Fred Hutchinson Cancer Center.

Looking at proteins circulating in the blood, the scientists found a set of molecules associated with inflammation that were present only in a subset of patients with long COVID and were not seen in those who recovered from their disease. The researchers published an article describing their findings in the journal Nature Communications today.

Out of 55 patients with long COVID, about two-thirds had persistently high levels of certain signals of inflammation. The scientists also looked at blood samples from 25 people who had COVID but recovered, and from 25 volunteers who had never had COVID to their knowledge. Those without long COVID did not show the same signs of inflammation in their blood.

Scientists have seen previous links between inflammation and long COVID, but the new study is the first to trace the persistence of these inflammatory markers over time in the same patients.

In those early days of the study, the scientists saw that certain immune responses – namely inflammation – were consistently high in these few patients with long COVID. In the patients that got sick and then recovered fully, inflammation levels went up as their bodies fought off the illness, and then went back down as they got better. In those with long COVID, the levels never went back down.

“Those patients with non-inflammatory long COVID might be living with permanent organ or tissue damage from their disease. That would require very different treatment from those with high levels of inflammation.”

Troy Torgerson, M.D., Ph.D., Director of Experimental Immunology at the Allen Institute for Immunology

The scientists also saw that these groups can't be distinguished based on symptoms alone. If anti-inflammatory drugs prove effective in treating inflammatory long COVID, patients would first need to be screened to determine which form of long COVID they have.

“We hope these findings provide features of long COVID that may guide potential future therapeutic approaches,”

Julie McElrath M.D., Ph.D. Senior Vice President and Director of Fred Hutch's Vaccine and Infectious Disease Division

Research article reference: Persistent serum protein signatures define an inflammatory subcategory of long COVID, Julie McElrath et al. Nature Communications.

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