Scientists Find Viral Traces in Blood That Could Finally Explain Long COVID

Scientists have discovered COVID-19 protein fragments lurking inside tiny cellular packages in the blood of long COVID patients, potentially offering the first measurable biomarker for this mysterious condition. The finding suggests the virus may persist in body tissues long after the initial infection, possibly explaining why symptoms can drag on for months or even years.

What Did Researchers Find in Long COVID Patients' Blood?

A team from the Translational Genomics Research Institute and Harbor-UCLA Medical Center analyzed blood samples from 14 long COVID patients over 12 weeks of exercise training, collecting 56 samples total. They discovered 65 distinct protein fragments from SARS-CoV-2 hidden inside extracellular vesicles—tiny, naturally occurring packages that help cells share proteins and other materials.

These fragments came from the virus's Pp1ab protein, an RNA replicase enzyme that's crucial for how the virus copies itself. "This protein is found uniquely in SARS-CoV-2, and not in uninfected human cells," noted Dr. Asghar Abbasi, the study's first author.

Could This Lead to Better Long COVID Diagnosis?

Currently, doctors diagnose long COVID based on a collection of symptoms that persist 12 weeks or more after 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," explained Dr. William Stringer, the study's senior author.

The viral fragments were found in each patient but not at every blood draw, and they weren't detected in pre-pandemic control samples. However, the researchers caution that the molecular signals were subtle and inconsistent, leaving important questions unanswered.

What Does This Mean for Understanding Long COVID?

Separate research has identified a distinct type of immune cell called LC-Mo (long COVID monocytes) that appears linked to persistent symptoms. These cells showed specific patterns associated with:

• Inflammatory Signaling: Persistent elevations of plasma proteins including CCL2, CXCL11, and tumor necrosis factor (TNF) that indicate ongoing inflammation
• Tissue Scarring Programs: Epigenetic changes that drive profibrotic programs, potentially leading to tissue damage and scarring
• Impaired Immune Response: Reduced ability to mount proper interferon responses when stimulated, suggesting compromised immune function

The LC-Mo state was particularly enriched in people who had mild-to-moderate acute COVID-19 infections and correlated with fatigue severity. In patients with severe respiratory symptoms, these cells showed higher expression levels and appeared in lung samples with a profibrotic profile.

"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 Dr. Patrick Pirrotte, co-senior author of the blood fragment study.

The researchers still don't know whether these fragments represent active viral replication or simply molecular "trash" left over from previous infection. Long COVID affects 10% to 20% of people after SARS-CoV-2 infection, with symptoms that can persist for over three years, making these potential biomarkers crucial for better understanding and treating the condition.