最新研究结果表明新冠肺炎康复者体内抗病毒抗体至少能稳定维持4个月

hantavirus

新冠病毒作为一种新发的烈性传染病毒，对其感染免疫的机理研究相对较少，之前有零星报道，提到康复患者中的中和抗体水平较低，且维持时间较短，这无疑对疫苗的研发带来挑战！近日，国际顶级医学期刊《新英格兰医学杂志》上发表了在冰岛的新冠肺炎临床数据，该项研究为迄今规模最大、随访时间最长、检测手段最多样，研究结果表明：新冠肺炎患者体内的抗病毒抗体在诊断后没有显著降低，而且至少能稳定保持4个月，这意味着人体对新冠病毒产生的免疫力可能不是短暂的。




新冠疫情爆发以来，最为大家关注的问题之一是：人类对新冠病毒的免疫力究竟能持续多久？这一方面关系到康复后是否会出现二次感染，另一方面关系到疫苗的效果。以往的研究表明，经核酸检测确认阳性之后，患者体内针对核蛋白（N）和刺突蛋白（S）的IgG抗体在21～28天内显著减少，针对三聚体S蛋白的抗体会在56天内显著减少。不过，之前的研究规模小，采用的检测方法也不够全面。因此，我们对于新冠肺炎患者体液免疫反应的性质和持久性所知有限。



本文采用6种抗体检测手段对30576名冰岛人的血清样本进行了检测。此外，研究人员还对1237名经过核酸检测确认感染新冠病毒的患者，进行了为期4个月的血清抗病毒抗体追踪检测。




▲ 研究流程



结果表明在经核酸检测确诊后的第25天，90%以上的康复者血清样本泛Ig抗体检测均呈阳性，在随后的100天里，血清抗体阳性患者的比例保持稳定。例如，IgM anti-N抗体水平在诊断后不久迅速上升，然后迅速下降，两个月后一般检测不到。IgA anti-S1抗体在诊断后一个月下降，此后仍可检测到。IgG anti-N和IgG anti-S1抗体水平在诊断后的前6周内上升，然后略有下降。





▲ 不同抗体滴度随时间的变化



此外，在本研究中，研究人员也发现抗病毒抗体水平在老年人和住院者中较高，女性患者体内pan-Ig anti-S1-RBD和IgA anti-S1水平较低。体重指数与抗体水平呈正相关；吸烟和使用抗炎药物与抗体水平较低相关。




▲ 抗体水平与临床特征之间的关系



总的来看，这项临床研究表明，新冠感染者体内的抗体水平没有显著降低，而且至少能稳定维持4个月，这与之前的研究数据差异明显。由于冰岛人群的感染率极低，研究人员认为抗体水平持久这个现象，应该不是二次感染导致的。


在随论文同期发表的评论文章中，麻省总医院Ragon研究所的两位专家对上述现象，给出了另一个解释。他们表示，病毒感染和注射疫苗其实会产生两波抗体。第一波是由早期的短命浆细胞产生的，但这一波在急性感染被解决后会迅速消退；而第二波抗体是由少量寿命较长的浆细胞产生的，这些浆细胞提供了长期的免疫力。




▲ 两波抗体产生示意图



不过，需要指出的是，抗新冠病毒抗体的水平虽然至少能稳定维持4个月，但是抗体的持续存在是否能给康复者提供持续的保护仍然未知。在疫苗的III期临床数据出炉之前，无疑这是各好消息！
附文献信息：

题目：Humoral Immune Response to SARS-CoV-2 in Iceland

DOI：10.1056/NEJMoa2026116

摘要：BACKGROUND：Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).METHODS：We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. RESULTS​：Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. CONCLUSIONS​：Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.