Trier Nicole Hartwig, Zivlaei Nadia, Ostrowski Sisse Rye, Sørensen Erik, Larsen Margit, Slibinskas Rimantas, Ciplys Evaldas, Frederiksen Jette Lautrup, Houen Gunnar
Department of Neurology, Rigshospitalet Glostrup, Valdemar Hansens vej 13, Glostrup, Denmark.
Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen OE, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, BLegdamsvej 3B, 2200 Copenhagen N, Denmark.
Immunol Lett. 2025 Aug;274:107004. doi: 10.1016/j.imlet.2025.107004. Epub 2025 Mar 27.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can have a serious course with many complications, especially in immunocompromised individuals. In such persons, other latent virus infections may contribute to disease pathology, in particular viruses which infect immune cells such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV).
In this study, serology-based assays were conducted to analyse antibody responses to SARS-CoV-2 spike protein (SP), EBV Epstein-Barr nuclear antigen (EBNA)-1 and CMV phosphoprotein (pp)52 in naturally SARS-CoV-2-infected individuals, non-infected healthy controls (HCs) and vaccinated healthy controls (VHCs) to identify an association between SARS-CoV-2 antibodies and EBV and CMV antibodies in order to determine whether latent EBV and CMV infected individuals are more prone to become infected with SARS-CoV-2. Moreover, SARS-CoV-2, EBV, and CMV antibody responses were characterized in serum from patients with relapsing-remitting multiple sclerosis (RRMS), a chronic inflammatory disease strongly associated with EBV infections, to determine whether the serologic virus antibody profile varies in immunocompromised RRMS individuals upon SARS-CoV-2 vaccinations compared to VHCs.
Significantly elevated SP IgG, IgM and IgA levels were identified in SARS-CoV-2-infected immunocompetent individuals when compared to non-infected HCs. However, no correlation was found to serum antibodies between SARS-CoV-2, EBV, and CMV in individuals infected with SARS-CoV-2 and in VHCs, suggesting that latent infections with neither EBV nor CMV associates to SARS-CoV-2 infection. Moreover, no significant difference in SP IgG, IgA and IgM levels was observed between vaccinated RRMS patients and VHCs, indicating that the immune system of immune deficient RRMS patients and VHCs respond identical to SARS-CoV-2 vaccinations.
Collectively, SARS-CoV-2 SP antibody levels reflect the vaccination and infection history and do not associate with EBV and CMV serostatus.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染可能病程严重并伴有许多并发症，尤其是在免疫功能低下的个体中。在这类人群中，其他潜伏病毒感染可能会导致疾病病理变化，特别是那些感染免疫细胞的病毒，如爱泼斯坦-巴尔病毒（EBV）和巨细胞病毒（CMV）。
在本研究中，采用基于血清学的检测方法，分析自然感染SARS-CoV-2的个体、未感染的健康对照（HCs）和接种疫苗的健康对照（VHCs）对SARS-CoV-2刺突蛋白（SP）、EBV爱泼斯坦-巴尔核抗原（EBNA）-1和CMV磷蛋白（pp）52的抗体反应，以确定SARS-CoV-2抗体与EBV和CMV抗体之间的关联，从而确定潜伏性EBV和CMV感染个体是否更易感染SARS-CoV-2。此外，还对复发缓解型多发性硬化症（RRMS）患者的血清中的SARS-CoV-2、EBV和CMV抗体反应进行了特征分析，RRMS是一种与EBV感染密切相关的慢性炎症性疾病，目的是确定与VHCs相比，免疫功能低下的RRMS个体在接种SARS-CoV-2疫苗后血清病毒抗体谱是否有所不同。
与未感染的HCs相比，在自然感染SARS-CoV-2的免疫功能正常个体中，SP IgG、IgM和IgA水平显著升高。然而, 在感染SARS-CoV-2的个体和VHCs中，未发现SARS-CoV-2、EBV和CMV血清抗体之间存在相关性，这表明EBV和CMV的潜伏感染与SARS-CoV-2感染均无关联。此外，接种疫苗的RRMS患者与VHCs之间的SP IgG、IgA和IgM水平未观察到显著差异，这表明免疫缺陷的RRMS患者和VHCs的免疫系统对SARS-CoV-2疫苗的反应相同。
总体而言，SARS-CoV-2 SP抗体水平反映了疫苗接种和感染史，与EBV和CMV血清状态无关。
