Blood Biomarker Test Could Confirm Long COVID Diagnosis

No blood tests or biomarkers currently exist to confirm the condition, leaving diagnosis largely presumptive. Now, a new study has uncovered a possible biological signal that could serve as the first specific, quantifiable indicator for the condition.

Researchers from the Translational Genomics Research Institute (TGen, Phoenix, AZ, USA;) have identified SARS-CoV-2 protein fragments within extracellular vesicles (EVs) in the blood of long COVID patients. EVs are tiny, naturally occurring packages that transport proteins, metabolites, and other materials between cells.

The study, reported in Infection, analyzed 56 blood samples from 14 patients over 12 weeks of aerobic exercise training in a long COVID clinical trial. Researchers found 65 distinct protein fragments from the virus’s Pp1ab protein, an RNA replicase enzyme essential for viral replication. This protein is unique to SARS-CoV-2 and not found in uninfected human cells.

Significantly, these viral peptides were demonstrated in each long COVID patient, though not in every sample taken, and were not detected in a separate control group of pre-pandemic EV samples. Their presence supports growing evidence that SARS-CoV-2 may persist in certain tissues long after acute infection. Some scientists suggest lingering viral reservoirs could contribute to the ongoing symptoms of long COVID.

The findings raise key questions about the nature of these peptides—whether they indicate ongoing viral replication or are merely residual “molecular trash” left after viral protein formation. The team has yet to test individuals without long COVID symptoms who have been infected with SARS-CoV-2, leaving the broader significance of the biomarker to be determined.

"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," said William Stringer, M.D., Lundquist Institute investigator and senior author of the study.

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