Background

There is a paucity of data on vaccine-induced or infection-induced (hybrid or natural) immunity against omicron (B.1.1.529) subvariant BA.2, particularly in comparing the effects of previous SARS-CoV-2 infection with the same or different genetic lineage. We aimed to estimate the protection against omicron BA.2 associated with previous primary infection with omicron BA.1 or pre-omicron SARS-CoV-2, among health-care workers with and without mRNA vaccination.

Methods

We conducted a test-negative case-control study among health-care workers aged 18 years or older who were tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 was the predominant variant and was presumptively diagnosed with a positive test result. We identified cases (positive test during study period) and controls (negative test during study period) using the provincial laboratory database that records all nucleic acid amplification testing for SARS-CoV-2 in Quebec, and used the provincial immunisation registry to determine vaccination status. Logistic regression models compared the likelihood of BA.2 infection or reinfection (second positive test ≥30 days after primary infection) among health-care workers who had previous primary infection and none to three mRNA vaccine doses versus unvaccinated health-care workers with no primary infection.

Findings

258 007 SARS-CoV-2 tests were done during the study period. Among those with a valid result and that met the inclusion criteria, there were 37 732 presumed BA.2 cases (2521 [6·7%] reinfections following pre-omicron primary infection and 659 [1·7%] reinfections following BA.1 primary infection) and 73 507 controls (7360 [10·0%] had pre-omicron primary infection and 12 315 [16·8%] had BA.1 primary infection). Pre-omicron primary infection was associated with a 38% (95% CI 19–53) reduction in BA.2 infection risk, with higher BA.2 protection among those who had also received one (56%, 95% CI 47–63), two (69%, 64–73), or three (70%, 66–74) mRNA vaccine doses. Omicron BA.1 primary infection was associated with greater protection against BA.2 infection (risk reduction of 72%, 95% CI 65–78), and protection was increased further among those who had received two doses of mRNA vaccine (96%, 95–96), but was not improved with a third dose (96%, 95–97).

Interpretation

Health-care workers who had received two doses of mRNA vaccine and had previous BA.1 infection were subsequently well protected for a prolonged period against BA.2 reinfection, with a third vaccine dose conferring no improvement to that hybrid protection. If this protection also pertains to future variants, there might be limited benefit from additional vaccine doses for people with hybrid immunity, depending on timing and variant.

Funding

Ministère de la Santé et des Services Sociaux du Québec.

中文翻译：

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在接种和未接种 mRNA 疫苗的医护人员中，预防原发性 omicron BA.1 或前 omicron SARS-CoV-2 感染带来的 omicron (B.1.1.529) BA.2 再感染：一项测试阴性病例对照研究

背景

关于疫苗诱导或感染诱导（混合或自然）针对 omicron (B.1.1.529) 亚变体 BA.2 的免疫的数据很少，特别是在比较先前 SARS-CoV-2 感染与相同病毒感染的效果方面。或不同的遗传谱系。我们的目的是评估在接种或未接种 mRNA 疫苗的医护人员中，对与先前原发感染 omicron BA.1 或 pre-omicron SARS-CoV-2 相关的 omicron BA.2 的保护作用。

方法

我们对 2022 年 3 月 27 日至 6 月 4 日期间在加拿大魁北克省接受 SARS-CoV-2 检测的 18 岁或以上的医护人员进行了一项测试呈阴性的病例对照研究，当时 BA.2 是主要病毒变异并被推定诊断为阳性测试结果。我们使用记录魁北克省所有 SARS-CoV-2 核酸扩增检测的省级实验室数据库确定了病例（研究期间检测呈阳性）和对照（研究期间检测呈阴性），并使用省免疫登记处确定疫苗接种状况。Logistic 回归模型比较了先前曾感染过原发感染且未接种过三剂 mRNA 疫苗的医护人员与未接种过原发感染的未接种疫苗的医护人员之间的 BA.2 感染或再感染（初次感染后 30 天以上的第二次阳性检测）的可能性。感染。

发现

研究期间进行了 258 007 次 SARS-CoV-2 检测。在具有有效结果且符合纳入标准的患者中，有 37 732 例疑似 BA.2 病例（2521 例 [6·7%] 为前微米原发感染后的再感染，659 例 [1·7%] 为 BA.1 后的再感染。原发感染）和 73 507 名对照（7360 [10·0%] 患有前微米原发感染，12 315 [16·8%] 患有 BA.1 原发感染）。前微米级原发感染与 BA.2 感染风险降低 38% (95% CI 19–53) 相关，同时接受过一次感染的患者的 BA.2 保护程度更高 (56%, 95% CI 47–63) )、两剂 (69%, 64–73) 或三剂 (70%, 66–74) mRNA 疫苗剂量。Omicron BA.1 原发感染与针对 BA.2 感染的更大保护相关（风险降低 72%，95% CI 65-78），并且在接受两剂 mRNA 疫苗的患者中，保护作用进一步增强（96%， 95-96），但第三剂后没有改善（96%，95-97）。

解释

接受过两剂 mRNA 疫苗且之前曾感染过 BA.1 的卫生保健工作者随后在很长一段时间内得到了良好的保护，免受 BA.2 的再次感染，而第三剂疫苗对这种混合保护没有任何改善。如果这种保护也适用于未来的变异，那么对于具有混合免疫的人来说，额外疫苗剂量的益处可能有限，具体取决于时间和变异。

资金

魁北克省卫生与社会服务部。