Hudák Anett, Pettko-Szandtner Aladár, Letoha Annamária, Letoha Tamás
Pharmacoidea Ltd., H-6726 Szeged, Hungary.
Biological Research Centre of the Hungarian Academy of Sciences, H-6726 Szeged, Hungary.
Int J Mol Sci. 2025 Aug 19;26(16):8007. doi: 10.3390/ijms26168007.
Vaccines played a crucial role in the COVID-19 pandemic, but their long-term biological effects and efficacy in vulnerable populations remain under intensive investigation. This study assessed clinical outcomes, comorbidities, and systemic biomarker and proteomic profiles in 366 multimorbid patients, stratified into four groups based on SARS-CoV-2 infection and vaccination status (COV+ vac+, COV+ vac-, COV- vac+, COV- vac-). Clinical and laboratory data, including comorbidities and relevant biomarkers, were collected. Proteomic analysis using mass spectrometry was performed to identify molecular changes associated with infection and vaccination. Statistical analyses examined associations between clinical status, biomarkers, and patient outcomes. As most participants received mRNA-based vaccines, the results primarily reflect responses to spike protein-expressing platforms. Biomarkers of cardiac and renal stress-namely proBNP and carbamide-were elevated in vaccinated individuals. Five deaths occurred in the COV+ vac+ group and two in the COV+ vac- group, most of which were attributed to exacerbations of pre-existing chronic diseases rather than to COVID-19 pneumonia. Protection against breakthrough infections waned over time, particularly beyond 200 days post-vaccination. Mass spectrometry identified proteins such as actin, fibrinogen chains, and SAA2 as potential diagnostic targets. Although the cross-sectional observational design limits the ability to draw causal inferences, the observed waning immunity and potential systemic alterations in vaccinated multimorbid patients highlight the importance of longitudinal follow-up to guide tailored immunization strategies and post-vaccination monitoring in high-risk groups.
疫苗在新冠疫情中发挥了关键作用，但其长期生物学效应以及在弱势群体中的有效性仍在深入研究中。本研究评估了366名患有多种疾病的患者的临床结局、合并症、全身生物标志物和蛋白质组学特征，这些患者根据感染新冠病毒和接种疫苗的状况分为四组（新冠病毒感染且接种疫苗、新冠病毒感染未接种疫苗、未感染新冠病毒接种疫苗、未感染新冠病毒未接种疫苗）。收集了包括合并症和相关生物标志物在内的临床和实验室数据。采用质谱法进行蛋白质组学分析，以识别与感染和接种疫苗相关的分子变化。统计分析研究了临床状况、生物标志物与患者结局之间的关联。由于大多数参与者接种的是基于信使核糖核酸的疫苗，结果主要反映了对表达刺突蛋白平台的反应。接种疫苗个体的心脏和肾脏应激生物标志物——即脑钠肽前体和尿素——升高。新冠病毒感染且接种疫苗组有5例死亡，新冠病毒感染未接种疫苗组有2例死亡，其中大多数归因于原有慢性病的加重，而非新冠病毒肺炎。对突破性感染的防护作用会随着时间减弱，尤其是在接种疫苗200天后。质谱法鉴定出肌动蛋白、纤维蛋白原链和血清淀粉样蛋白A2等蛋白质为潜在诊断靶点。尽管横断面观察性设计限制了得出因果推断的能力，但在接种疫苗的患有多种疾病的患者中观察到的免疫力减弱和潜在的全身改变凸显了纵向随访对于指导高危人群量身定制免疫策略和接种后监测的重要性。
