ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1672485
This article is part of the Research TopicPattern Recognition Receptors: Balancing Inflammation and Immune HomeostasisView all 6 articles
Severe COVID-19 induces prolonged elevation of the acute-phase protein pentraxin 3 (PTX-3)
Provisionally accepted
Bernhard Kratzer
Robert B StiegerSeyma DurmusDoris Trapin
Pia Gattinger
Paul EttelAl Nasar Ahmed Sehgal
Kristina BorochovaYulia Dorofeeva
Inna Tulaeva
Katharina Grabmeier-PfistershammerPeter A TauberMarika Gerdov
Thomas Perkmann
Ingrid Fae
Sabine Wenda
Michael Kundi
Sebastian Wrighton
Gottfried Fischer
Rudolf Valenta*
Winfried F Pickl*- Medical University of Vienna, Vienna, Austria
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During the acute-phase of COVID-19, elevated levels of several acute-phase proteins, such as Creactive 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. In this study, we assessed 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 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. 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.
Keywords: COVID-19, Pentraxin-3, Soluble pattern recognition receptors, Acute-Phase Proteins, Severe COVID-19
Received: 24 Jul 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Kratzer, Stieger, Durmus, Trapin, Gattinger, Ettel, Sehgal, Borochova, Dorofeeva, Tulaeva, Grabmeier-Pfistershammer, Tauber, Gerdov, Perkmann, Fae, Wenda, Kundi, Wrighton, Fischer, Valenta and Pickl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Rudolf Valenta, Medical University of Vienna, Vienna, Austria
Winfried F Pickl, Medical University of Vienna, Vienna, Austria
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