Unraveling Long COVID: Could Excessive Inflammation be the Missing Piece of the Puzzle?

by Tatsuya Nakamura
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Recent research by the Allen Institute and Fred Hutchinson Cancer Center points to an amplified inflammatory response as a potential explanation for many long COVID instances. This discovery indicates that select anti-inflammatory medications might ease symptoms for certain long COVID sufferers, advancing the concept of personalized medicine in managing this disease.

Understanding the molecular traces of this chronic condition could offer critical clues for directing clinical trials and designing treatment plans.

The Allen Institute and Fred Hutchinson Cancer Center’s research suggests that an escalated inflammatory response could be at the core of many long COVID cases.

The researchers pinpointed a particular group of molecules related to inflammation by studying proteins present in the bloodstream. These molecules were exclusively detected in a specific group of long COVID patients and were not present in individuals who had fully recovered from the virus. The findings are elaborated in an article recently published in the journal Nature Communications.

Among 55 patients suffering from long COVID, around two-thirds showed persistently high levels of certain inflammatory signals. Blood samples from 25 individuals who had recovered from COVID and 25 volunteers who had never contracted the virus to their knowledge were also studied. Those without long COVID did not exhibit similar inflammation signs in their blood.

The volunteers for this new analysis are participating in a larger, ongoing study based in Fred Hutch, the Seattle COVID Cohort Study, led by Julie McElrath, M.D., Ph.D., and Julie Czartoski, ARNP.

Elevated serum proteins 60 days after the onset of SARS-CoV-2 symptoms reveal a sub-category of long-COVID associated with enduring inflammation. This signature highlights biological diversity in long-COVID, underscoring the need for targeted treatment strategies and providing diagnostic utility for differentiating inflammatory and non-inflammatory long-COVID. Credit: Rachel Tompa, Ph.D. / Allen Institute

While earlier studies have linked inflammation to long COVID, this new research is the first to track the ongoing presence of these inflammatory markers in the same patients over time.

Troy Torgerson, M.D., Ph.D., points to a clear inference from these results: certain types of anti-inflammatory drugs could potentially lessen symptoms for some long COVID patients. However, doctors need a method to determine which long COVID patients could benefit from specific treatments — a step towards precision medicine for a disease that continues to be frustratingly elusive.

“The central question was whether we could identify which long COVID patients have chronic inflammation versus those that don’t. Such information would be beneficial for planning clinical trials and assisting clinicians in developing targeted treatments for their patients,” stated Torgerson, who spearheaded the Nature Communications publication along with McElrath and others.

The blood markers discovered in this subset of “inflammatory long COVID” patients suggest a type of inflammation akin to that seen in autoimmune diseases like rheumatoid arthritis. This inflammation might be treatable with an existing class of drugs called JAK inhibitors, though this has not yet been confirmed for long COVID.

The researchers aim to further refine their molecular signature of “inflammatory long COVID” to a handful of markers that could be used in clinical practice to differentiate these patients from others.

Developing more nuanced treatment methods

Inaugurated in early 2020, shortly after the COVID-19 pandemic led to widespread closures across the U.S., the Seattle COVID Cohort Study initially aimed to track immune responses over time in mild to moderate COVID patients. The objective was to capture the specifics of a “successful” immune response that resulted in a complete recovery.

However, the researchers soon noted

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