Covid-19 Breakthrough Infections in Vaccinated Health Care Workers.
Covid-19 Breakthrough Infections in Vaccinated Health Care Workers.
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DOI：
10.1056/nejmoa2109072
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发表时间：
2021-10-14
期刊：
影响因子：
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通讯作者：
Regev-Yochay G
中科院分区：
文献类型：
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作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
尽管BNT 162 b2信使RNA疫苗对严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）具有很高的疗效，但仍有罕见的突破性感染报告，包括医护人员中的感染。需要数据来表征这些感染并定义突破和感染性的相关性。在以色列最大的医疗中心，我们通过对有症状（包括轻度症状）或已知感染暴露的医护人员进行广泛评估，确定了突破性感染。这些评价包括流行病学调查、重复逆转录酶-聚合酶链反应（RT-PCR）测定、抗原检测快速诊断试验（Ag-RDT）、血清学测定和基因组测序。在病例对照分析中评估了突破性感染的相关性。我们将在SARS-CoV-2检测前一周内（感染围期）获得抗体滴度的突破性感染患者与4至5名未感染的对照组进行匹配，并使用广义估计方程预测病例和对照组之间的几何平均滴度以及两组滴度之间的比值。我们还评估了中和抗体滴度和N基因循环阈值（Ct）值之间的相关性。在有RT-PCR数据的1497名完全接种疫苗的卫生保健工作者中，记录了39例SARS-CoV-2突破性感染。中和抗体滴度的情况下，患者在围感染期低于匹配的未感染的对照组（病例对照比，0.361，95%置信区间，0.165至0.787）。较高的围感染中和抗体滴度与较低的感染性（较高的Ct值）相关。大多数突破性病例是轻度或无症状的，尽管19%有持续症状（>6周）。B.1.1.7（alpha）变异体在85%的检测样本中被发现。共有74%的病例患者在感染期间的某个时间点具有高病毒载量（Ct值，<30）;然而，在这些患者中，仅17例（59%）在并发Ag-RDT上具有阳性结果。未记录继发感染。在完全接种疫苗的卫生保健工作者中，SARS-CoV-2突破性感染的发生与感染围期的中和抗体滴度相关。大多数突破性感染是轻微的或无症状的，尽管确实发生了持续的症状。
Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case–control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.