"Introduction
... Our study uniquely combines clinical, demographic, and proteomic data to investigate both the impact of COVID-19 infection and the effects of vaccination, with a focus on elderly and multimorbid populations in a clinically well-characterized cohort from the Epidemiological Care Center of the University of Szeged...
Additionally, we aimed to identify key biomarkers that may improve diagnostic accuracy and enhance risk stratification. By examining proteomic changes associated with SARS-CoV-2 infection and vaccination, we uncovered molecular signatures that may support the development of personalized treatment strategies and enable the effective monitoring of long-term health outcomes...
2.1. Clinical Characteristics of Patients
Blood samples were collected between March 2022 and spring 2023, a period when SARS-CoV-2 infections in Hungary were overwhelmingly caused by Omicron subvariants (BA.1, BA.2, BA.4, and BA.5). Accordingly, the COV+ group primarily represents Omicron-era cases. A total of 366 patients were included...
The cohort was stratified according to both COVID-19 and vaccination status: 222 individuals were COV+ vac+, 95 were COV+ vac−, 40 were COV− vac+, and 9 were COV− vac−...
2.5. Vaccination, Comorbidities, and Parameter Correlations
... Significant positive correlations were found between vaccination status and proBNP (r = 0.24, p < 0.0001), CRP (r = 0.113, p = 0.034), and carbamide (r = 0.301, p < 0.0001), suggesting links between vaccination status and markers of cardiac stress (proBNP), inflammation (CRP), and renal function (carbamide)...
3. Discussion
... [O]ur data suggest that SARS-CoV-2 infection and vaccination—especially with mRNA-based COVID-19 vaccines—are associated with distinct patterns of inflammation, coagulation, and organ function in elderly and multimorbid individuals...
Among the clearest signals, elevated proBNP levels were consistently associated with vaccination, even at a mean post-vaccination interval of over 240 days. ProBNP is a recognized biomarker of cardiac stress, routinely used to assess heart failure and thromboembolic risk. Elevated proBNP has also been linked to increased mortality in COVID-19, independent of baseline cardiac conditions. In our cohort, vaccinated individuals—predominantly mRNA vaccine recipients—displayed sustained proBNP elevation, consistent with chronic, low-grade myocardial stress. This aligns with prior reports of post-vaccination cardiac complications, including myocarditis and pericarditis, especially following mRNA vaccination. Persistence well beyond expected immune activation windows is consistent with ongoing subclinical inflammation, endothelial dysfunction, or immune-mediated cardiac strain, possibly linked to repeated spike protein exposure. Notably, linear regression analysis showed that proBNP elevation was significantly associated with vaccination status (β = 1750, p = 0.0103), but not with pre-existing CVD (β = 654.5, p = 0.3179), indicating that the observed elevation in vaccinated individuals is unlikely to be driven solely by underlying heart conditions...
Carbamide levels were also significantly higher in vaccinated SARS-CoV-2-positive individuals (p < 0.0001), consistent with renal stress or heightened protein catabolism from combined effects of infection and vaccination. While impaired renal function is known to elevate proBNP levels, this explanation appears unlikely to fully account for our findings. Renal disease prevalence was actually higher among unvaccinated individuals (11.71%) than vaccinated ones (7.63%), making renal dysfunction an unlikely sole explanation for both carbamide and proBNP patterns. This further supports the possibility of a vaccination-associated component...
5. Conclusions
This study demonstrates that both SARS-CoV-2 infection and spike protein-expressing COVID-19 vaccination are associated with distinct systemic alterations at the clinical, biochemical, and proteomic levels. Acute infection was linked to classical inflammatory and innate immune activation, whereas vaccinated individuals—sampled on average 210+ days after their last, predominantly spike-expressing vaccine dose—exhibited a molecular profile suggestive of low-grade inflammation, procoagulant activity, complement activation, and vascular remodeling. These post-vaccination associations were detectable across diverse clinical backgrounds and occurred independently of acute illness."
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