Scientific reportsApr 17, 2026

Unique blood protein patterns 3 months after COVID-19 infection, regardless of ongoing symptoms

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

Plasma proteomic changes persisted 3 months after SARS-CoV-2 infection regardless of post-COVID condition, with additional oxidative stress and inflammatory differences in PCC.

Evidence

This plasma proteomics study using DIA-MS compared uninfected, convalescent, and PCC samples and found a distinct post-infection proteome, lower PRDX6, higher VNN1 and PON3, higher six proteins linked to glycolysis/complement/coagulation/inflammation in PCC, and higher 8-OHdG with lower GSH and GSSG in PCC.

Caveat

The abstract states that ELISA validation did not necessarily match the proteomics findings, so some protein-level signals remain uncertain and need alternate validation.

Simplified

Persistent symptoms following SARS-CoV-2 infection are the hallmark of post-COVID condition (PCC), also referred to as long COVID. However, the underlying molecular mechanisms remain poorly understood. In this study, we employed data-independent acquisition mass spectrometry (DIA-MS)-based plasma proteomics to identify molecular alterations associated with PCC. DIA-MS proteomic analysis revealed a clear distinction between the plasma proteome of uninfected individuals and those previously infected with SARS-CoV-2, irrespective of PCC status. PCC samples demonstrated downregulation of the antioxidant protein peroxiredoxin 6 (PRDX6) and upregulation of oxidative stress-associated proteins, particularly vanin-1 (VNN1) and paraoxonase-3 (PON3). Additionally, individuals with PCC exhibited significantly elevated levels of six proteins-PCSK9, CST3, C1Q, CPB2, KNG1, and GAPDH-associated with glycolysis, complement and coagulation cascades, and inflammatory pathways. Validation by ELISA does not necessarily reflect the proteomics data suggesting the requirement for alternate methods of validation. Nonetheless, oxidative stress, as measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG), further showed that PCC samples had significantly higher levels of DNA damage, compared with convalescent individuals. Antioxidant markers, including reduced and oxidized glutathione (GSH and GSSG), were significantly lower in PCC samples than in uninfected controls. Collectively, these findings indicate that plasma proteomic alterations persist for at least 3 months following SARS-CoV-2 infection, with additional disruptions in oxidative stress and inflammatory pathways characterizing individuals with PCC.