新冠疫情期间肾移植受者的体液疫苗反应和突破性感染：一项全国性队列研究
Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study.
作者信息
Hovd Markus, Åsberg Anders, Munthe Ludvig A, Heldal Kristian, Reisæter Anna V, Vaage John T, Lund-Johansen Fridtjof, Midtvedt Karsten
机构信息
Department of Transplantation Medicine, Oslo University Hospital, Norway.
Department of Pharmacy, University of Oslo, Norway.
出版信息
EClinicalMedicine. 2023 Jun;60:102035. doi: 10.1016/j.eclinm.2023.102035. Epub 2023 Jun 6.
BACKGROUND
Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs.
METHODS
We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4-10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway.
FINDINGS
The study included 3607 KTRs (59 [48-70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3-4] vaccines (range 2-6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31-57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference.
INTERPRETATION
Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic.
FUNDING
CEPI and internal funds.
背景
肾移植受者（KTRs）对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗的反应降低，且患重症冠状病毒病2019（COVID-19）的风险增加。目前尚不清楚疫苗诱导的抗受体结合域免疫球蛋白G（抗RBD IgG）水平是否与预防COVID-19感染及感染后的生存情况相关。我们旨在评估疫苗反应对KTRs中突破性感染（BTI）风险和COVID-19死亡的影响。
方法
我们开展了一项全国性研究，调查SARS-CoV-2感染、COVID-19相关/非相关死亡的竞争风险，以及每次接种疫苗后4至10周通过抗RBD IgG反应水平评估的疫苗效力。该研究纳入了2020年2月20日在挪威存活且移植肾功能正常的所有KTRs，2022年11月11日之后的事件进行右删失处理。纳入了一个2019年1月1日至2020年1月1日的疫情前参考队列以评估超额死亡率。该研究在挪威奥斯陆大学医院Rikshospitalet进行。
结果
该研究纳入了3607名KTRs（年龄59[48 - 70]岁），其移植肾在2020年2月20日功能正常，接受了（中位数[四分位间距]）4[3 - 4]剂疫苗（范围2 - 6剂，99%为信使核糖核酸（mRNA）疫苗）。在3213名KTRs提供的12701份血清样本中检测了抗RBD IgG。在接种疫苗41[31 - 57]天后评估疫苗反应。共有1090名KTRs感染了SARS-CoV-2，其中1005例（92%）为BTI，疫苗反应并不能预防BTI。在比较疫苗反应水平（≥5与≥5000 BAU/mL）时，感染后40天COVID-19相关死亡的风险比为1.71（95%置信区间：1.14，2.56）。与2019年疫情前参考队列相比，SARS-CoV-2感染存活的KTRs中未记录到超额非COVID-19死亡率。
解读
我们的研究结果表明，SARS-CoV-2 mRNA疫苗反应不能预测对感染的预防作用，但可预防KTRs中致命疾病的进展，且更高的疫苗反应进一步降低了COVID-19死亡风险。在疫情期间未观察到超额非COVID-19死亡率。
资金来源
流行病防范创新联盟（CEPI）和内部资金。
Zotero 插件