Thread by @ZdenekVrozina

A new Scientific Reports study adds an important nuance to the long COVID conversation. The biggest difference was not between people with PCC and without PCC, but between uninfected people and everyone who had recovered from SARS2🧵

Long COVID may be part of a broader post-infectious biological spectrum, where symptomatic PCC represents the more clinically visible end of a continuous dysregulation rather than a completely separate category.

That matters, because a lot of people still think in very rigid categories here. But instead of two clean boxes - recovered vs long COVID - the biology may look more like a continuum.

The study looked at plasma proteins 3 months after mild, non hospitalized COVID-19. The cohort included 35 uninfected controls, 62 convalescent individuals without PCC, and 53 people with PCC.

What they found is striking. People who had COVID still showed a distinct plasma proteome compared with uninfected controls at 3 months. But PCC and convalescent participants overlapped a lot.

It may actually be the point. If long COVID is a heterogeneous post-infectious syndrome, overlap is exactly what you would expect.

In that framework, PCC may not be a totally separate biological state. It may be the more symptomatic, more clinically apparent end of a shared post-infectious process.

The oxidative stress findings fit that model well. Both post-infection groups had lower glutathione (GSH) than uninfected controls, suggesting reduced antioxidant reserve even outside overt PCC.

But the PCC group showed stronger signs of ongoing redox stress, including lower PRDX6, higher PON3 and VNN1, and higher 8-OHdG, a marker of oxidative DNA damage.

So this does not look like some people have biology, others just have symptoms. It looks more like a shared post-infectious shift, with symptom burden emerging where that dysregulation is stronger, more persistent, or less well compensated.

The study also found signals in complement, coagulation, inflammation, and metabolic pathways - including CPB2, C1Q, KNG1, GAPDH, CST3, and PCSK9. That adds to the case that long COVID has a real systemic biological footprint.

Reason to be cautious. ELISA validation was only partly consistent with the proteomics. Several markers were not robustly replicated across methods.

Real value of this study is not a ready-made biomarker, but broader idea - post COVID biology may persist even in people who do not currently meet criteria for PCC, while symptomatic PCC may reflect the more clinically visible edge of that same continuum. @szupraha @ZdravkoOnline @adamvojtech86

That also means the overlap between PCC and convalescent groups should not automatically be dismissed as noise. It may reflect the reality of a dynamic, layered, post infectious syndrome rather than a clean binary state.

We need true longitudinal tracking of the same people over time.

Still, this paper is important. Long COVID may be less about crossing a sharp biological line, and more about where someone sits on a post-infectious spectrum of ongoing dysregulation.

Chowdhury at al., Distinct plasma proteome signature at 3 months post-COVID-19 infection irrespective of post-COVID condition. nature.com/articles/s4159…