Researchers say they have made a major breakthrough in efforts to truly identify “Long Covid”.

The team from the Translational Genomics Research Institute (TGen), part of City of Hope, and the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Centre has revealed they have identified a potential biomarker for long COVID.

If the findings of their study are confirmed by other research centres, the biomarker could be the first specific and quantifiable indicator for confirming long COVID. Currently, clinicians confer a diagnosis of long COVID based upon a collection of symptoms that patients develop after SARS-CoV-2 infection.

“If a patient arrives in clinic and they relate the persistence of typical signs and symptoms of long COVID, 12 weeks or more after COVID -19 infection, I give them a presumptive diagnosis, but I don’t have any blood tests or biomarkers to confirm this diagnosis,” said William Stringer, a Lundquist Institute investigator and senior author on the study.

The study results detail the detection of SARS-CoV-2 protein fragments within extracellular vesicles (EVs) — tiny, naturally occurring packages that help cells share proteins, metabolites, and other materials. The researchers collected and analysed blood samples from 14 patients over 12 weeks of aerobic exercise training (56 samples in all) in a clinical trial led by Stringer in long COVID.

The researchers found 65 distinct protein fragments from SARS-CoV-2 inside the EVs. These fragments come from the virus’s Pp1ab protein, an RNA Replicase enzyme which is key to how the virus copies itself and makes other viral particles. This protein is found uniquely in SARS-CoV-2, and not in uninfected human cells, noted Asghar Abbasi, a Lundquist Institute investigator and first author of the study.

Significantly, the researchers found that these viral peptides were demonstrated in each subject, but not each blood draw, in the EVs of Long COVID patients and were not detected in a separate control group of pre-pandemic EV samples.

These findings add to growing evidence that suggests that SARS-CoV-2 may persist in certain body tissues long after the initial infection. Some groups hypothesize these lingering viral reservoirs could play a role in Long COVID. How the virus reaches tissues without its usual entry points—such as the brain—remains an open question, and may be related to EV particles.

“We thought that maybe if the virus is circulating or moving in the body, we should try to see if EVs are carrying those viral fragments,” Abbasi explained.

“While promising, the molecular signal of the viral peptides within the study samples was observed to be subtle and not consistently detected at every blood collection time point,” said Patrick Pirrotte, associate professor at TGen, director of the Integrated Mass Spectrometry Shared Resource at TGen and City of Hope, and co-senior author of the study. “There’s still a lot to unpack that we don’t know at this point.”

“We haven’t run [our tests] on people without long COVID symptoms who are currently, or who were, infected with COVID,” said Stringer. “This raises the question: is this just continuing to take out the trash from the COVID infected cell or is this really ongoing replication someplace? I think that’s the mechanistic issue that needs to be resolved in future studies.”