tetano
Editor, Senior Moderator
Front Immunol
. 2025 Oct 1:16:1672485.
doi: 10.3389/fimmu.2025.1672485. eCollection 2025. Severe COVID-19 induces prolonged elevation of the acute-phase protein pentraxin 3
Bernhard Kratzer[SUP] 1 [/SUP], Robert B Stieger[SUP] 1 [/SUP], Seyma Durmus[SUP] 1 [/SUP], Doris Trapin[SUP] 1 [/SUP], Pia Gattinger[SUP] 2 [/SUP], Paul Ettel[SUP] 1 [/SUP], Al Nasar Ahmed Sehgal[SUP] 1 [/SUP], Kristina Borochova[SUP] 2 [/SUP], Yulia Dorofeeva[SUP] 2 [/SUP], Inna Tulaeva[SUP] 2 3 4 [/SUP], Katharina Grabmeier-Pfistershammer[SUP] 1 [/SUP], Peter A Tauber[SUP] 1 [/SUP], Marika Gerdov[SUP] 5 [/SUP], Thomas Perkmann[SUP] 5 [/SUP], Ingrid Fae[SUP] 6 [/SUP], Sabine Wenda[SUP] 6 [/SUP], Michael Kundi[SUP] 7 [/SUP], Sebastian Wrighton[SUP] 1 [/SUP], Gottfried F Fischer[SUP] 6 [/SUP], Rudolf Valenta[SUP] 2 3 4 8 9 [/SUP], Winfried F Pickl[SUP] 1 9 [/SUP]
Affiliations
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.
Keywords: COVID-19; acute-phase proteins; pentraxin-3; severe COVID-19; soluble pattern recognition receptors.
. 2025 Oct 1:16:1672485.
doi: 10.3389/fimmu.2025.1672485. eCollection 2025. Severe COVID-19 induces prolonged elevation of the acute-phase protein pentraxin 3
Bernhard Kratzer[SUP] 1 [/SUP], Robert B Stieger[SUP] 1 [/SUP], Seyma Durmus[SUP] 1 [/SUP], Doris Trapin[SUP] 1 [/SUP], Pia Gattinger[SUP] 2 [/SUP], Paul Ettel[SUP] 1 [/SUP], Al Nasar Ahmed Sehgal[SUP] 1 [/SUP], Kristina Borochova[SUP] 2 [/SUP], Yulia Dorofeeva[SUP] 2 [/SUP], Inna Tulaeva[SUP] 2 3 4 [/SUP], Katharina Grabmeier-Pfistershammer[SUP] 1 [/SUP], Peter A Tauber[SUP] 1 [/SUP], Marika Gerdov[SUP] 5 [/SUP], Thomas Perkmann[SUP] 5 [/SUP], Ingrid Fae[SUP] 6 [/SUP], Sabine Wenda[SUP] 6 [/SUP], Michael Kundi[SUP] 7 [/SUP], Sebastian Wrighton[SUP] 1 [/SUP], Gottfried F Fischer[SUP] 6 [/SUP], Rudolf Valenta[SUP] 2 3 4 8 9 [/SUP], Winfried F Pickl[SUP] 1 9 [/SUP]
Affiliations
- PMID: 41103408
- PMCID: PMC12520919
- DOI: 10.3389/fimmu.2025.1672485
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.
Keywords: COVID-19; acute-phase proteins; pentraxin-3; severe COVID-19; soluble pattern recognition receptors.