Table_1_Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes.xlsx

Autoantibodies to multiple targets are found during acute COVID-19. Whether all, or some, persist after 6 months, and their correlation with sustained anti-SARS-CoV-2 immunity, is still controversial. Herein, we measured antibodies to multiple SARS-CoV-2 antigens (Wuhan-Hu-1 nucleoprotein (NP), whole spike (S), spike subunits (S1, S2 and receptor binding domain (RBD)) and Omicron spike) and 102 human proteins with known autoimmune associations, in plasma from healthcare workers 8 months post-exposure to SARS-CoV-2 (n=31 with confirmed COVID-19 disease and n=21 uninfected controls (PCR and anti-SARS-CoV-2 negative) at baseline). IgG antibody responses to SARS-CoV-2 antigens were significantly higher in the convalescent cohort than the healthy cohort, highlighting lasting antibody responses up to 8 months post-infection. These were also shown to be cross-reactive to the Omicron variant spike protein at a similar level to lasting anti-RBD antibodies (correlation r=0.89). Individuals post COVID-19 infection recognised a common set of autoantigens, specific to this group in comparison to the healthy controls. Moreover, the long-term level of anti-Spike IgG was associated with the breadth of autoreactivity post-COVID-19. There were further moderate positive correlations between anti-SARS-CoV-2 responses and 11 specific autoantigens. The most commonly recognised autoantigens were found in the COVID-19 convalescent cohort. Although there was no overall correlation in self-reported symptom severity and anti-SARS-CoV-2 antibody levels, anti-calprotectin antibodies were associated with return to healthy normal life 8 months post infection. Calprotectin was also the most common target for autoantibodies, recognized by 22.6% of the overall convalescent cohort. Future studies may address whether, counter-intuitively, such autoantibodies may play a protective role in the pathology of long-COVID-19.

急性新型冠状病毒肺炎（COVID-19）感染期间可检测到针对多种靶标的自身抗体。目前对于这些自身抗体是否全部或部分在感染6个月后仍持续存在，以及其与持续抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）免疫的相关性，仍存在争议。
本研究中，我们于暴露于SARS-CoV-2 8个月后采集医护人员的血浆样本，检测其针对多种SARS-CoV-2抗原【包括武汉-Hu-1株核蛋白（NP）、全长刺突蛋白（S）、刺突亚基（S1、S2及受体结合域（RBD））以及奥密克戎（Omicron）株刺突蛋白】以及102种已被证实与自身免疫相关的人类蛋白的抗体水平；其中确诊COVID-19病例31例，基线时PCR及抗SARS-CoV-2抗体均为阴性的未感染对照21例。
相较于健康对照组，新冠康复队列中针对SARS-CoV-2抗原的IgG抗体应答水平显著更高，表明感染后8个月仍存在持久的抗体应答。上述抗体对奥密克戎株刺突蛋白同样具有交叉反应性，其反应水平与持久的抗RBD抗体水平相当（相关系数r=0.89）。
新冠感染个体可识别一组共同的自身抗原，与健康对照组相比，该组自身抗原具有群体特异性。此外，长期抗刺突蛋白IgG水平与新冠感染后的自身反应广度呈显著相关。抗SARS-CoV-2抗体应答与11种特定自身抗原之间还存在中等程度的正相关。最常被识别的自身抗原在新冠康复队列中得以检出。
尽管自我报告的症状严重程度与抗SARS-CoV-2抗体水平之间未发现总体相关性，但抗钙卫蛋白抗体与感染后8个月恢复正常健康生活状态显著相关。钙卫蛋白同时也是自身抗体最常见的靶标，在全部康复队列中有22.6%的个体可检测到针对该靶标的自身抗体。未来研究可进一步探讨：与直觉相悖的是，此类自身抗体是否在长新冠（long-COVID-19）的病理进程中发挥保护作用。