Is Long-COVID related to Overactive Inflammation?

News

Is Long-COVID related to Overactive Inflammation?

Is Long-COVID related to Overactive Inflammation?

New research from the Allen Institute and Fred Hutchinson Cancer Center suggests that an increased inflammatory response may be at the root of many Long-COVID cases.

By examining the proteins found in the blood, the researchers identified a specific group of molecules involved in inflammation.

Notably, these molecules were only detected in a certain group of long-term COVID patients, not in those who had fully recovered from the virus.

The team’s findings are detailed in a recent article published in the journal Nature Communications:

Of the 55 Long-COVID patients, about two-thirds had persistently high levels of certain inflammatory signals.

The scientists also studied blood samples from 25 people who had COVID but recovered, as well as 25 volunteers who, to their knowledge, never had COVID.

Those without Long-COVID did not show the same signs of inflammation in their blood.

Patient volunteers in the new analysis were based on part of a larger, ongoing study by Fred Hatch, the Seattle COVID Cohort Study, which was led by Fred Hatch’s senior vice president and vaccine with Julie McElrath, MD, director of the Division of Infectious Diseases, and Julie Czartoski, MD, Hatch’s research clinician, ARNP lead.

Is Long-COVID related to Overactive Inflammation?

Circulating serum proteins 60 days after the onset of infectious symptoms of SARS CoV 2 identify a Long-COVID subcategory with persistent inflammation. This feature helps clarify the biodiversity of Long-COVID, highlights the need for targeted therapeutic strategies, and demonstrates diagnostic utility for distinguishing between inflammatory and non-inflammatory Long-COVID. Source: Rachel Tompa, Ph.D. / Allen Institute

Scientists have seen a link between inflammation and Long-COVID before, but the new study is the first to track these markers of inflammation long-term in the same patients.

The findings have an obvious implication, said Troy Torgerson, MD, director of experimental immunology at the Allen Institute for Immunology, part of the Allen Institute: Certain classes of anti-inflammatory drugs may ease symptoms in some long-term COVID patients. symptom.

But doctors need a way to tell which Long-COVID patients might benefit from which treatment — a kind of precision medicine for a so far still maddeningly mysterious disease.

“The big question is, can we define which Long-COVID patients have persistent inflammation and which don’t?” said Torgerson, who worked with McElrath, Aarthi Talla, senior bioinformatician at the Allen Institute for Immunology, and former senior bioinformatician.

Scientist Dr. Suhas Vasaikar (now Chief Scientist at Seagen Corporation) led the Nature Communications publication together with former Executive Vice President and Director Dr. Tom Bumol.

Specifically, blood markers found in this subgroup of “inflammatory Long-COVID” patients, as the scientists call them, point to a flavor of inflammation similar to that seen in autoimmune diseases such as rheumatoid arthritis. This inflammation can be treated with an existing class of drugs called JAK inhibitors, at least in the case of rheumatoid arthritis (it has not been tested for Long-COVID).

The scientists also hope to narrow down the molecular signature of their “inflammatory Long-COVID” to a few markers that could be used clinically to separate this subset of Long-COVID patients from others.

Treatment plan

Launched in spring 2020, shortly after the COVID-19 pandemic shut down businesses and schools across the U.S., the Fred Hatch-led Seattle COVID cohort study was originally designed to track immune responses in patients with mild or moderate COVID . The idea is to capture the details of a “successful” immune response — one in which patients don’t get too sick, don’t need to be hospitalized, and make a full recovery.

But the team soon realized that even among those who didn’t get super ill, not everyone recovered. In initial work in 2020 to track details of the immune responses of 18 COVID patients, scientists found that symptoms persisted in a small number of people, an early example of what would eventually be called long-term COVID, or just long-term COVID.

Early in the study, the scientists saw that certain immune responses — namely inflammation — were consistently high in these small numbers of long-term COVID patients. In patients who got sick and then fully recovered, inflammation levels rose as their bodies fought off the disease, and then fell back as their condition improved. In those with long-term COVID, inflammation levels never went back down.

So the team decided to expand their study to look at more patients with long-term COVID, focusing on 1,500 proteins circulating in the blood. These assays revealed distinct molecular “barrels” of Long-COVID, inflammatory and non-inflammatory Long-COVID. Understanding the molecular roots of the disease, or a subset of the disease, will help guide clinical trial design and eventual treatment decisions, the scientists said.

“The ultimate goal is to treat patients,” Talla said. “Although we call everything Long-COVID, the results of this work tell us that we may not be able to provide the same kind of therapy to everyone, and that we should not treat it for the sake of treatment.” Put everyone into a group. “

Those with noninflammatory Long-COVID may live with permanent organ or tissue damage from their disease, Torgerson said. This will require very different treatment than those with high levels of inflammation. The scientists also saw that the groups could not be distinguished based on symptoms alone.

If anti-inflammatory drugs prove to be effective in treating inflammatory Long-COVID, patients will first need to be screened to determine which form of Long-COVID they have. It is hoped that these findings provide a characterization of Long-COVID that can guide potential future treatments.