目前，患者感染严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）后，机体免疫状况随时间的纵向变化及其与临床结局的关联尚不明确。因此，我们致力于研究新冠病毒特异性抗体[免疫球蛋白G（IgG）和免疫球蛋白M（IgM）]随时间变化的特征，并分析特异性抗体、炎性细胞因子及其与新冠病毒肺炎（COVID-19，简称新冠肺炎）患者的生存状况之间的关联。研究共招募了1830例实验室确诊的新冠肺炎感染病例。利用局部加权回归散点平滑法（LOWESS）拟合患者自发病以来直至12周的病毒载量、特异性抗体及细胞因子水平随时间的变化谱。通过中介分析，探究细胞因子在抗体应答与生存状况之间的中介效应。在1830例患者中，新冠病毒核酸阳性患者共1435例，新冠病毒特异性IgG和（或）IgM抗体阳性患者为395例。在1435例患者中，2.4%的患者在住院期间既未出现IgG也未出现IgM的血清学转变。特异性IgG和IgM的血清阳性率在发病后的第1周分别为29.6%和48.1%，并在5周内达到峰值。对于痊愈出院患者组，在发病后的12周内，IgM水平缓慢下降，而IgG水平基本维持在188 AU· mL⁻¹左右。反之，对于最终进展为死亡的患者，其IgM水平迅速下降，IgG水平在第12周也下降至87 AU· mL⁻¹。与出院患者组相比，病亡患者组的白细胞介素6（IL-6）、白细胞介素8（IL-8）、白细胞介素10（IL-10）、白细胞介素1β（IL-1β）、白细胞介素2受体（IL-2R）及肿瘤坏死因子-α（TNF-α）水平均较高，IgG水平与死亡风险之间12.5%的关联由上述细胞因子介导。本研究阐明了新冠病毒特异性抗体自发病以来12周内的实时变化特征，并表明了抗体应答对生存结局的积极作用，相关发现对新冠肺炎患者的预后评估可能有所帮助。

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the associations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for
SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL 1 for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU mL 1 at the twelfth week. Elevated interleukin-6, interleukin-8, interleukin-10, interleukin-1b, interleukin-2R, and tumor necrosis factor-a levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.