Background

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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接种疫苗的医护人员中出现 Covid-19 突破性感染

 背景

尽管 BNT162b2 信使 RNA 疫苗针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 具有高效能，但仍报告了罕见的突破性感染，包括医护人员中的感染。需要数据来描述这些感染的特征并定义突破性和感染性的相关性。

 方法

在以色列最大的医疗中心，我们通过对有症状（包括轻微症状）或已知感染暴露的医护人员进行广泛评估，发现了突破性感染。这些评估包括流行病学调查、重复逆转录聚合酶链反应（RT-PCR）测定、抗原检测快速诊断测试（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（感染期）内获得抗体滴度的突破性感染患者与四到五名未感染的对照进行匹配，并使用广义估计方程来预测病例和对照之间的几何平均滴度以及两组滴度之间的比率。我们还评估了中和抗体滴度和 N 基因周期阈值 (Ct) 值与感染性之间的相关性。

 结果

在可获得 RT-PCR 数据的 1497 名完全接种疫苗的医护人员中，记录了 39 例 SARS-CoV-2 突破性感染。病例患者在感染前后的中和抗体滴度低于匹配的未感染对照（病例与对照比率，0.361；95%置信区间，0.165至0.787）。较高的感染周围中和抗体滴度与较低的感染性（较高的 Ct 值）相关。尽管 19% 的病例有持续症状（>6 周），但大多数突破性病例均为轻度或无症状。 85% 的测试样本中发现了 B.1.1.7 (alpha) 变体。总共 74% 的病例患者在感染过程中的某个时刻存在高病毒载量（Ct 值，<30）；然而，在这些患者中，只有 17 名 (59%) 的同时 Ag-RDT 呈阳性结果。没有记录继发感染。

 结论

在完全接种疫苗的医护人员中，SARS-CoV-2 突破性感染的发生与感染期间的中和抗体滴度相关。尽管确实出现了持续症状，但大多数突破性感染都是轻微或无症状的。