Severe COVID-19 induces prolonged elevation of the acute-phase protein pentraxin 3, 2025, Kratzer et al.

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Frontiers | Severe COVID-19 induces prolonged elevation of the acute-phase protein pentraxin 3

IntroductionDuring the acute-phase of COVID-19, elevated levels of several acute-phase proteins, such as C-reactive protein (CRP), mannose-binding lectin (MB...

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Bernhard Kratzer, Robert B Stieger, Seyma Durmus, Doris Trapin, Pia Gattinger, Paul Ettel, Al Nasar Ahmed Sehgal, Kristina Borochova, Yulia Dorofeeva, Inna Tulaeva, Katharina Grabmeier-Pfistershammer, Peter A Tauber, Marika Gerdov, Thomas Perkmann, Ingrid Fae, Sabine Wenda, Michael Kundi, Sebastian Wrighton, Gottfried Fischer, Rudolf Valenta, Winfried F Pickl

Introduction: During the acute-phase of COVID-19, elevated levels of several acute-phase proteins, such as C-reactive protein (CRP), mannose-binding lectin (MBL), pentraxin 3 (PTX-3), serum amyloid A (SAA) and surfactant protein D (SP-D), are associated with severe to fatal clinical outcomes. Typically, these markers return to baseline within days after resolution of the acute infection.

Methods: In this study, we assessed the plasma levels of these proteins in a well-defined cohort of 141 COVID-19 convalescent patients 10 weeks after infection and compared them to 98 non-infected controls. In addition, we performed genetic analyses in a subgroup of patients and related the findings with structural equation modelling to disease severity.

Results: In contrast to other acute-phase proteins, PTX-3 levels were significantly higher in severe COVID-19 convalescent patients than in the control group. Furthermore, a higher proportion of patients with severe COVID-19 exhibited PTX-3 levels above 5000 pg/ml even 10 months post-infection, compared to those with mild disease. To explore potential genetic influences, a genetic analysis was performed on all severely affected patients (n=36) and on an age- and sex-matched subset of mild COVID-19 patients (n=38). Results revealed a significantly higher frequency (p<0.0001) of the homozygous wildtype genotype of the PTX-3 SNP rs971145291 in severe (15 out of 36) versus mild (1 out of 38) COVID-19 patients. Using structural equation modelling, the association of this PTX-3 genotype and disease severity was shown to be mediated by elevated PTX-3 levels, with no contribution from other analyzed (clinical) confounders.

Discussion: In summary, severe COVID-19 patients show high PTX-3 serum levels which may be influenced by genetic predisposition, specifically the absence of the rs971145291 SNP variant. PTX-3 may thus serve both as a biomarker for tissue damage and/or long-term immune activation and eventually post-COVID-19 complications.

 

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Potential biomarker for the development of long COVID identified | MedUni Vienna

www.meduniwien.ac.at

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A research team at MedUni Vienna found that levels of the immune protein PTX-3 remain significantly elevated in patients who had severe COVID-19, even up to ten months after infection. This suggests PTX-3 could serve as a biomarker for long-term tissue damage, immune activation, and post-COVID complications such as ME/CFS. The study involved 141 recovered COVID-19 patients and 98 uninfected controls, comparing their levels of acute phase proteins over time. Unlike most such proteins that normalize after infection, PTX-3 remained high in severe cases, indicating possible ongoing repair or viral remnants. These findings, published in Frontiers in Immunology, add valuable insight into the long-term effects of COVID-19 and highlight the need for further research.

 

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Press release:

Potential biomarker for the development of long COVID identified | MedUni Vienna

www.meduniwien.ac.at

Potential biomarker for the development of long COVID identified​

Study provides new insights into the mechanisms of SARS-CoV-2 infections

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(Vienna, 01 October 2025) A research team working at MedUni Vienna has demonstrated that a specific component of the immune system (PTX-3) remains at significantly higher levels in the blood of patients who have suffered from severe COVID-19, even months after the acute infection has subsided. This study identified PTX-3 as a potential biomarker for existing tissue damage, long-term immune activation and also for complications following COVID-19. The resultswere published in the top-journal "Frontiers in Immunology" and make an important contribution to a better understanding of the consequences of COVID-19. Importantly, they may point to another possible cause of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Within this study, the research groups led by Winfried Pickl and Rudolf Valenta (both from the Center for Pathophysiology, Infectiology and Immunology at MedUni Vienna) examined the levels of so-called acute phase proteins in the blood of 141 COVID-19 convalescent patients ten weeks and ten months after acute infection. These were then compared with levles from 98 uninfected control subjects. Acute phase proteins are components of the innate immune system that are rapidly released into circulation during infections to ward off infections and control associated inflammatory and repair processes. During the acute phase of COVID-19, elevated serum levels of several such proteins from this group are associated with severe to fatal clinical outcomes. As a rule, these markers return to their baseline values within a few days after the acute infection has subsided. However, the current study has shown for the first time that this is not the case for pentraxin 3 (PTX-3).

The research team's investigations revealed that PTX-3 levels were significantly higher in convalescent COVID-19 patients who had experienced a severe disease course persisting ten weeks post infection. In addition, some of these patients still had significantly higher PTX-3 levels ten months after the acute phase when compared to patients with mild disease or uninfected control subjects. "We assume that the higher PTX-3 levels either indicate ongoing tissue repair mechanisms or could hint at the presence of persistent SARS-CoV-2 remnants in the body," says Winfried Pickl. "PTX-3 could thus serve as a biomarker for long-lasting tissue damage and/or long-term immune activation resulting in possible complications after COVID-19," adds Rudolf Valenta.

Previous studies have already described PTX-3 as a marker for severe COVID-19 in its acute stage. The current results indicate that the protein could also play a role in long-term recovery. "Scientits have already linked long-lasting immune activation due to ongoing repair processes and residual virus components in the body to the development of long COVID-19. Our study constitutes important additional insights into these mechanisms," said the study's first author, Bernhard Kratzer. Further research is needed to better understand COVID-19 pathophysiology, its long-term consequences, and to confirm these new findings in prospective studies.

Publication: Frontiers in Immunology
Severe COVID-19 induces prolonged elevation of the acute-phase protein pentraxin 3.
Bernhard Kratzer, Robert B. Stieger, Seyma Durmus, Doris Trapin, Pia Gattinger, Paul Ettel, Al Nasar Ahmed Sehgal, Kristina Borochova, Yulia Dorofeeva, Inna Tulaeva, Katharina Grabmeier-Pfistershammer, Peter A. Tauber, Marika Gerdov, Thomas Perkmann, Ingrid Fae, Sabine Wenda, Michael Kundi, Sebastian Wrighton, Gottfried F. Fischer, Rudolf Valenta* and Winfried F. Pickl*.
DOI: 10.3389/fimmu.2025.1672485