Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2). We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates. A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44–0·67) in CPRD GOLD, 0·48 (0·34–0·68) in CPRD AURUM, 0·71 (0·55–0·91) in SIDIAP, and 0·59 (0·40–0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60–1·20] in CPRD GOLD and 0·84 [0·74–0·94] in CPRD AURUM). Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults. National Institute for Health and Care Research.

中文翻译：

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COVID-19 疫苗预防长期新冠症状的有效性：对英国、西班牙和爱沙尼亚数据的交错队列研究


尽管疫苗已被证明可以有效预防严重的 COVID-19，但其对预防长期症状的作用尚未完全了解。我们的目的是评估疫苗接种对预防长期新冠肺炎症状的总体效果，并评估最常用疫苗（ChAdOx1 和 BNT162b2）的相对有效性。我们使用来自英国（临床实践研究数据链 [CPRD] GOLD 和 AURUM）、西班牙加泰罗尼亚（初级保健研究信息系统 [SIDIAP]）的初级保健记录以及爱沙尼亚的国家健康保险索赔（ CORIVA 数据库）。截至 2021 年 1 月 4 日（英国）、2021 年 2 月 20 日（西班牙）和 2021 年 1 月 28 日（爱沙尼亚）登记至少 180 天的所有成年人均构成源人口。疫苗接种状态被用作随时间变化的暴露情况，并与疫苗推出期交错。接种疫苗的人根据接种的第一剂剂量按疫苗品牌进一步分类。长期COVID的主要结局定义是在PCR阳性检测或临床诊断出COVID-19之日起90至365天内至少出现世界卫生组织列出的25种症状中的一种，并且180天内没有该症状的病史SARS-Cov-2 感染之前。对每个队列分别应用倾向得分重叠加权，以最大程度地减少混杂。计算次分布风险比 (sHR) 以估计疫苗对长期新冠病毒的有效性，并使用阴性对照结果进行经验校准。对交错队列进行随机效应荟萃分析，以汇总总体效应估计。 总共有 1 618 395 (CPRD GOLD)、5 729 800 (CPRD AURUM)、2 744 821 (SIDIAP) 和 77 603 (CORIVA) 接种者以及 1 640 371 (CPRD GOLD)、5 860 564 (CPRD A)乌鲁姆） 、2 588 518 (SIDIAP) 和 302 267 (CORIVA) 未接种疫苗的人被包括在内。与未接种疫苗的人相比，接种第一剂任何 COVID-19 疫苗的人的长期 COVID 症状的总体 HR 在 CPRD GOLD 中为 0·54 (95% CI 0·44–0·67)，在 CPRD GOLD 中为 0·48 (0·48)。 CPRD AURUM 中为 34–0·68)，SIDIAP 中为 0·71 (0·55–0·91)，CORIVA 中为 0·59 (0·40–0·87)。首剂 BNT162b2 的预防效果比 ChAdOx1 稍强（CPRD GOLD 中的 sHR 为 0·85 [0·60–1·20]，CPRD AURUM 中的 sHR 为 0·84 [0·74–0·94]） 。针对 COVID-19 的疫苗接种持续降低了长期出现新冠肺炎症状的风险，这突显了疫苗接种对于预防持续性新冠肺炎症状（尤其是成人）的重要性。国家健康与护理研究所。