Humoral Response Profile in SARS-CoV‑2 Infection: Differences across Virus Strains and Influenza

The clinical manifestation of COVID-19 after SARS-CoV-2 infection varies greatly, with many patients requiring intensive care due to complications like acute respiratory distress syndrome, reduced respiratory system compliance, and altered iron metabolism, which can be mistaken for worsening Influenza A infection. This highlights the need to study the humoral immune response to better understand the pathophysiology of viral respiratory infections and improve treatments and diagnostics. This study analyzed autoantibody and acute-phase reactant profiles in patients infected with SARS-CoV-2 and Influenza A using customized protein microarrays for sensitive and reproducible results. The findings revealed a significant increase in autoantibodies in SARS-CoV-2 patients, including those targeting calcitonin-related polypeptides, hepatocyte growth factor, or interleukin 8, compared to Influenza A patients, who showed elevated levels of selectin E and surfactant protein D. Additionally, most acute-phase reactants were higher in SARS-CoV-2 patients. The serological profile showed that the wild-type SARS-CoV-2 strain induced both IgM and IgG responses to all viral proteins, while other strains triggered an IgG response only at a later stage. Multiomics factor analysis identified key factors driving variation in COVID-19’s heterogeneous disease presentation. These insights offer valuable information for developing vaccines and therapeutic strategies against SARS-CoV-2.

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染后引发的新型冠状病毒肺炎（COVID-19）临床表现差异显著，大量患者会因急性呼吸窘迫综合征、呼吸系统顺应性下降、铁代谢异常等并发症需接受重症监护，此类表现易被误诊为甲型流感（Influenza A）病情恶化。这凸显了开展体液免疫应答研究的必要性，以更好地阐释病毒性呼吸道感染的病理生理学机制，并优化治疗与诊断手段。本研究采用定制化蛋白质微阵列（protein microarrays），对SARS-CoV-2感染者与甲型流感感染者的自身抗体及急性期反应物谱进行分析，以获取灵敏且可重复的实验结果。研究结果表明，与甲型流感患者相比，SARS-CoV-2感染者体内自身抗体水平显著升高，包括靶向降钙素相关多肽、肝细胞生长因子以及白细胞介素8（interleukin 8）的自身抗体；而甲型流感患者体内则表现为选择素E（selectin E）与表面活性蛋白D（surfactant protein D）水平升高。此外，多数急性期反应物在SARS-CoV-2感染者体内水平更高。血清学特征分析显示，野生型SARS-CoV-2毒株可诱导机体针对所有病毒蛋白的IgM与IgG应答，而其他毒株仅在感染后期触发IgG应答。多组学因子分析明确了驱动新冠异质性疾病表现的关键影响因素。上述研究发现为开发针对SARS-CoV-2的疫苗与治疗策略提供了极具价值的参考信息。