do Nascimento Lais Alves, Machado NicolleRakanidis, Borges João Vitor da Silva, Fagundes Beatriz Oliveira, Bergamasco Isabella Siuffi, Sgnotto Fabio da Ressureição, Bachi André Luis Lacerda, Sato Maria Notomi, Victor Jefferson Russo
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil.
School of Medicine, Santo Amaro University (UNISA), São Paulo, Brazil.
Front Immunol. 2025 Sep 3;16:1668223. doi: 10.3389/fimmu.2025.1668223. eCollection 2025.
The contribution of antibody-mediated responses to COVID - 19 outcomes remains unclear, particularly regarding cross-reactivity with unrelated pathogens. While co-infections are known to influence disease progression, the broader landscape of IgG reactivity during SARS-CoV-2 infection has not been systematically explored.
We employed a high-density peptide microarray containing 4,344 linear epitopes from 37 viruses, 27 bacteria, 17 parasites, and 8 fungi to characterize serum IgG repertoires from individuals with moderate (n = 39) or severe (n = 40) COVID - 19. Controls included pre-pandemic healthy donors and a pooled intravenous immunoglobulin (IVIg) formulation. Data analysis included intensity ranking, epitope mapping, and comparative analysis of mean signal intensities for each epitope between the COVID-Mod and COVID-Sev groups.
COVID - 19 patients showed widespread IgG reactivity against diverse pathogens, with patterns differing by disease severity. Severe cases displayed broader and more intense reactivity, notably against hepatitis C virus (HCV), SARS-CoV-1, influenza A, Mycobacterium tuberculosis, and Plasmodium falciparum. Moderate cases showed preferential recognition of epitopes from HTLV-I, Neisseria meningitidis, and Trypanosoma cruzi. These findings suggest that SARS-CoV-2 infection modulates pre-existing humoral memory, possibly through epitope spreading or immune reprogramming.
SARS-CoV-2 infection reshapes the IgG epitope repertoire in a severity-dependent manner, extending to antigens from unrelated pathogens. This phenomenon may reflect underlying immune dysregulation or idiotype-driven interactions. Comprehensive profiling of pathogen-related IgG responses may reveal potential biomarkers of disease severity. This phenomenon may inform future investigations aimed at improving personalized management strategies for co-infected or immunocompromised patients.
抗体介导的反应对新冠病毒疾病结局的贡献仍不明确，尤其是与无关病原体的交叉反应。虽然已知合并感染会影响疾病进展，但尚未系统探索严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染期间IgG反应性的更广泛情况。
我们采用了一种高密度肽微阵列，其包含来自37种病毒、27种细菌、17种寄生虫和8种真菌的4344个线性表位，以表征中度（n = 39）或重度（n = 40）新冠病毒疾病患者的血清IgG库。对照组包括疫情前的健康供体和一种静脉注射免疫球蛋白（IVIg）混合制剂。数据分析包括强度排名、表位定位以及新冠病毒疾病中度组和重度组之间每个表位的平均信号强度比较分析。
新冠病毒疾病患者显示出针对多种病原体的广泛IgG反应性，其模式因疾病严重程度而异。重症病例表现出更广泛、更强的反应性，特别是针对丙型肝炎病毒（HCV）、SARS-CoV-1、甲型流感、结核分枝杆菌和恶性疟原虫。中度病例表现出对人嗜T淋巴细胞病毒I型（HTLV-I）、脑膜炎奈瑟菌和克氏锥虫表位的优先识别。这些发现表明，SARS-CoV-2感染可能通过表位扩展或免疫重编程来调节预先存在的体液免疫记忆。
SARS-CoV-2感染以严重程度依赖的方式重塑IgG表位库，扩展到来自无关病原体的抗原。这种现象可能反映了潜在的免疫失调或独特型驱动的相互作用。对病原体相关IgG反应的全面分析可能揭示疾病严重程度的潜在生物标志物。这一现象可能为未来旨在改善合并感染或免疫功能低下患者个性化管理策略的研究提供信息。
