Table 2_Severity-dependent IgG epitope profiling in COVID-19 reveals differential recognition of pathogen-derived antigens.xlsx

BackgroundThe 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.
MethodsWe 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.
ResultsCOVID - 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.
ConclusionsSARS-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.

背景：抗体介导的免疫应答对新型冠状病毒病（COVID-19）转归的贡献仍未明确，尤其是在与无关病原体的交叉反应性方面。尽管已有研究证实合并感染可影响疾病进程，但目前尚未对新型冠状病毒（SARS-CoV-2）感染期间的IgG反应性全景进行系统探究。
方法：本研究采用高密度肽微阵列（high-density peptide microarray），该芯片搭载了来自37种病毒、27种细菌、17种寄生虫及8种真菌的4344个线性表位，用于表征中度（n=39）与重度（n=40）COVID-19患者的血清IgG抗体谱。对照组设置为大流行前健康供者及混合静脉注射免疫球蛋白（intravenous immunoglobulin, IVIg）制剂。数据分析包括信号强度排序、表位定位，以及对中度COVID-19组（COVID-Mod）与重度COVID-19组（COVID-Sev）各表位的平均信号强度开展比较分析。
结果：COVID-19患者针对多种病原体呈现出广泛的IgG反应性，且反应模式随疾病严重程度存在差异。重度患者展现出更广泛且更强的反应性，尤其针对丙型肝炎病毒（HCV）、严重急性呼吸综合征冠状病毒1型（SARS-CoV-1）、甲型流感病毒、结核分枝杆菌及恶性疟原虫。中度患者则优先识别人类T淋巴细胞病毒I型（HTLV-I）、脑膜炎奈瑟菌及克氏锥虫的表位。上述结果提示，SARS-CoV-2感染可调控预先存在的体液免疫记忆，该过程可能通过表位扩散或免疫重编程实现。
结论：SARS-CoV-2感染以疾病严重程度依赖性方式重塑IgG表位谱，其反应范围可延伸至无关病原体的抗原。该现象或反映潜在的免疫失调或独特型介导的相互作用。对病原体相关IgG应答进行全面谱式分析，或可揭示疾病严重程度的潜在生物标志物。这一发现可为未来旨在优化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借鉴。