23 Jan 2026 2 min read longcovid

Possible long COVID biomarker: identification of SARS-CoV-2 related proteins in Serum Extracellular Vesicles

A new study reports that fragments of SARS-CoV-2 proteins can still be detected in the blood of people with Long COVID more than a year after infection.

Photo by National Cancer Institute / Unsplash

Plain-Language Summary

This study investigates whether fragments of SARS-CoV-2, the virus that causes COVID-19, can still be detected in the blood of people with Long COVID long after their initial infection. The researchers focused on extracellular vesicles (EVs), which are very small membrane-bound particles released by cells that transport proteins and genetic material throughout the body. EVs are increasingly studied because they can reflect ongoing biological processes and disease activity.

Blood samples were collected from 14 adults with persistent Long COVID symptoms, such as fatigue, shortness of breath, and post-exertional malaise, an average of about 17 months after their initial infection. Using high-sensitivity mass spectrometry, the researchers analyzed EVs isolated from blood samples taken at rest and during exercise. They specifically searched for peptides (short protein fragments) that are unique to SARS-CoV-2.

The analysis detected multiple SARS-CoV-2-derived peptides, particularly from a viral replication protein called polyprotein 1ab (Pp1ab), in EVs from all Long COVID participants. These viral peptides were not found in EVs collected from control samples obtained before the COVID-19 pandemic. The findings suggest that EVs may carry persistent viral components long after acute infection and could potentially serve as measurable markers of ongoing viral-related processes in Long COVID.

Key Findings

SARS-CoV-2-derived peptides were detected in serum extracellular vesicles from all Long COVID participants studied.
A total of 65 unique viral peptides mapped to polyprotein 1ab, a protein essential for viral RNA replication.
A conserved peptide from non-structural protein 3 (nsp3) was confirmed in 12 of 14 participants using targeted mass spectrometry.
Viral peptides were detected across multiple time points, including samples collected during exercise.
No SARS-CoV-2 peptides were detected in pre-pandemic control samples.
The identified viral peptide was conserved across major SARS-CoV-2 variants, including Alpha, Delta, and Omicron.

Study Type

Observational laboratory study using proteomic analysis of blood-derived extracellular vesicles.

What This Means (and Doesn’t Mean)

The findings support the possibility that components of SARS-CoV-2 may persist in the body of some people with Long COVID and be transported through extracellular vesicles. This provides a potential biological explanation for ongoing immune activation and suggests that EV-associated viral peptides could be explored as biomarkers for Long COVID in future studies.

However, this study involved a small number of participants and does not prove that the detected viral material is infectious or directly responsible for symptoms. It also does not establish how common this phenomenon is among all people with Long COVID or whether targeting these viral components would improve clinical outcomes.

Source

Journal article: https://link.springer.com/article/10.1007/s15010-025-02612-x

Disclaimer

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