Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Vaccine. 2024 May 31;42(15):3455-3460. doi: 10.1016/j.vaccine.2024.04.044. Epub 2024 Apr 23.
Previous research suggested that the inactivated influenza vaccine (IIV) may protect against SARS-CoV-2 infection or a severe course of COVID-19. These findings were however based on cohort studies, that are prone to confounding by indication. We examined the association between IIV and SARS-Cov-2 infection in a Dutch population using a test-negative design.
This test-negative case-control study was conducted in adults (≥60) who tested because of COVID-19 like symptoms at community SARS-CoV-2 testing locations in the Netherlands during the period of November 8th 2021-March 11th 2022. Information on receipt of IIV in October-November 2021 was routinely collected at each visit. Logistic regression was used to calculate unadjusted, partially (sex, age, education level) and fully adjusted (COVID-19 vaccination, IIV 2020) odds ratios (ORs) for receipt of IIV in SARS-CoV-2 positive versus negative subjects. Differential effects on SARS-CoV-2 risk by time since IIV were investigated by including an interaction term for calendar time: November 2021-January 2022 vs February-March 2022.
In total, 1,832 participants were included in the main analysis, of whom 336 (18.3 %) had a positive SARS-CoV-2 test. No significant association between IIV and SARS-CoV-2 infection was found; fully adjusted OR of 1.07 (95 % CI: 0.78-1.49). The interaction term for time periods was not significant (1.04 [95 % CI: 0.51-2.15], p = 0.91). Results were robust in sensitivity analyses.
While earlier observational studies suggested a protective non-specific effect of IIV and SARS-CoV-2 infections, this smaller, but well controlled test-negative design study does not suggest an effect, either positive or negative. Larger test-negative design studies, or alternative designs such as the self-controlled case series design are needed to confirm these findings and provide more definite answers on the topic.
先前的研究表明，灭活流感疫苗（IIV）可能对 SARS-CoV-2 感染或 COVID-19 重症病例有保护作用。然而，这些发现是基于队列研究的，这些研究容易受到指示性偏倚的影响。我们使用阴性病例对照设计，在荷兰人群中研究了 IIV 与 SARS-CoV-2 感染之间的关联。
本阴性病例对照研究在 2021 年 11 月 8 日至 2022 年 3 月 11 日期间，在荷兰社区 SARS-CoV-2 检测点因 COVID-19 样症状接受检测的成年人（≥60 岁）中进行。在每次就诊时，常规收集 2021 年 10 月至 11 月期间接受 IIV 的信息。使用逻辑回归计算 SARS-CoV-2 阳性与阴性受试者中接受 IIV 的未调整、部分（性别、年龄、教育程度）和完全调整（COVID-19 疫苗接种、2020 年 IIV）比值比（OR）。通过包含日历时间的交互项来研究 IIV 后时间对 SARS-CoV-2 风险的差异影响：2021 年 11 月至 2022 年 1 月与 2022 年 2 月至 3 月。
共有 1832 名参与者纳入主要分析，其中 336 名（18.3%）SARS-CoV-2 检测呈阳性。未发现 IIV 与 SARS-CoV-2 感染之间存在显著关联；完全调整后的 OR 为 1.07（95%CI：0.78-1.49）。时间期间的交互项不显著（1.04[95%CI：0.51-2.15]，p=0.91）。敏感性分析结果稳健。
虽然早期的观察性研究表明 IIV 和 SARS-CoV-2 感染具有非特异性保护作用，但这项规模较小但控制较好的阴性病例对照设计研究并未表明存在阳性或阴性作用。需要更大的阴性病例对照设计研究或替代设计，如自我对照病例系列设计，以证实这些发现并就该主题提供更明确的答案。
