Kratzer et al. (2025)
- Authors: 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, Winfried F. Pickl.
- Institutes: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Laboratory for Immunopathology, Department of Clinical Immunology and Allergology, IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; Life Improvement by Future Technologies (LIFT) Center, Moscow, Russia; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria; Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, Vienna, Austria; Department for Environmental Health, Center for Public Health, Medical University of Vienna, Vienna, Austria; Center for Molecular Allergology, Karl Landsteiner University, Krems, Austria; Karl Landsteiner University of Health Sciences, Krems, Austria.
- Publisher: Frontiers in Immunology
- Link: DOI
Summary
This study reveals that a specific inflammatory protein, PTX-3, can remain abnormally high for up to 10 months after a severe COVID-19 infection, long after other markers of acute illness have normalized. This suggests that the body may still be dealing with the after-effects of the virus, such as repairing damaged tissue. The research also found a genetic link, indicating that some individuals may be predisposed to both a more severe illness and this prolonged inflammatory signal. For patients with post-viral conditions, this identifies a potential objective biomarker (PTX-3) that reflects the long-lasting impact of a viral infection on the innate immune system.
What was researched?
This study investigated the long-term plasma levels of five acute-phase proteins (CRP, MBL, PTX-3, SAA, and SP-D) in patients who had recovered from COVID-19. The researchers aimed to determine if these markers remained elevated months after infection, how their levels related to the initial disease severity, and whether genetic factors could explain any persistent changes.
Why was it researched?
During an acute COVID-19 infection, high levels of these proteins are associated with severe disease, but they are expected to return to normal within days of recovery. It was unclear if COVID-19 could have a lasting impact on these innate immune factors. This research was motivated by the need to understand the long-term immunological consequences of the infection, particularly in patients who experienced severe illness.
How was it researched?
This was a case-control study involving 141 COVID-19 convalescent patients (105 with mild and 36 with severe disease) and 98 non-infected controls. Researchers measured the plasma levels of the five proteins at 10 weeks and again at 10 months post-infection. In a subgroup of 36 severe and 38 mild patients, they performed genetic sequencing of the PTX-3 gene to identify single nucleotide polymorphisms (SNPs) and used statistical modeling to connect genetics, protein levels, and disease severity.
What has been found?
At 10 weeks post-infection, only pentraxin 3 (PTX-3) levels were significantly higher in convalescent patients compared to controls, an effect driven primarily by the severe COVID-19 group. While PTX-3 levels generally decreased by 10 months, a significantly higher percentage of severe patients still maintained very high levels. The study identified a strong association between a specific genetic variation (the homozygous wildtype A/A genotype at SNP rs971145291) and severe disease, and this relationship was shown to be mediated by its effect on raising PTX-3 levels.
Discussion
The authors acknowledge several limitations, including the assessment at only two time points, the loss of some severe cases to follow-up, and the lack of genetic sequencing for the control group. They also note that the study was conducted early in the pandemic, so the findings may not apply to newer variants or vaccinated individuals. The prolonged elevation of PTX-3 is theorized to result from a combination of genetic predisposition and ongoing biological processes, such as tissue repair after severe lung damage.
Conclusion & Future Work
The authors conclude that PTX-3 can serve as a long-term, retrospective biomarker for severe COVID-19, with its prolonged elevation being partly determined by a person’s genetic makeup. They suggest PTX-3 may be a marker for sustained immune activation or tissue damage. Future studies are needed to explore its potential role in Long COVID and to validate the genetic findings in larger, more diverse cohorts.