Association Between Immune Dysfunction and COVID-19 Breakthrough Infection After SARS-CoV-2 Vaccination in the US
Association Between Immune Dysfunction and COVID-19 Breakthrough Infection After SARS-CoV-2 Vaccination in the US
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DOI：
10.1001/jamainternmed.2021.7024
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发表时间：
2021-12-28
影响因子：
39
通讯作者：
Patel, Rena C.
中科院分区：
文献类型：
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作者：
Sun, Jing;Zheng, Qulu;Patel, Rena C.
免疫功能障碍的人患严重COVID-19结果的风险更高。然而，这些患者在很大程度上被排除在SARS-CoV-2疫苗临床试验之外，造成了很大的证据缺口。目的确定在有或没有免疫功能障碍的人群中接种SARS-CoV-2疫苗后COVID-19突破性感染的发病率和发病率比（IRR）。该合作伙伴关系开发了一个安全的、基于电子病历的COVID-19临床数据库，这些数据来自美国各地的学术医疗中心。在2020年12月10日至2021年9月16日期间至少接种了1剂SARS-CoV-2疫苗的人被纳入样本。主要结果和指标疫苗接种、COVID-19诊断、免疫功能障碍诊断（即HIV感染、多发性硬化、类风湿性关节炎、实体器官移植和骨髓移植）、其他合并症，通过N3 C数据飞地访问人口统计数据。突破性感染定义为在接种疫苗第14天或之后感染的COVID-19感染，使用具有稳健SE的泊松回归评估了有或无免疫功能障碍的患者在完全或部分接种疫苗后的风险。Poisson回归模型控制了研究期间（2021年6月20日[Delta变体前或后]之前或之后）、完全疫苗接种状态、疫苗接种前COVID-19感染、人口统计学特征、地理位置和合并症负担。这些患者的中位（IQR）年龄为51（34-66）岁，主要为女性（n = 378 307 [56.9%]）。总体而言，在完全接种疫苗的人群中，COVID-19突破性感染的发病率为每1000人月5.0例，但在Delta变体成为主要SARS-CoV-2毒株后，发病率更高（2021年6月20日之前与之后的发病率，2.2 [95% CI，2.2-2.2] vs 7.3 [95% CI，7.3-7.4]/1000人月）。与部分疫苗接种相比，完全疫苗接种与突破性感染风险降低28%相关（校正IRR [AIRR]，0.72; 95%CI，0.68-0.76）。在完全接种疫苗后发生突破性感染的人更有可能是老年人和女性。HIV感染者（AIRR，1.33; 95% CI，1.18-1.49），类风湿性关节炎（AIRR，1.20; 95% CI，1.09-1.32）和实体器官移植（AIRR，2.16; 95%可信区间，1.96-2.38）结论和相关性这项队列研究发现，全面接种疫苗与降低COVID风险相关。19突破性感染，无论患者的免疫状态如何。尽管接种了全面疫苗，但免疫功能障碍的人发生COVID-19突破性感染的风险远高于没有这种情况的人。对于免疫功能障碍的患者，即使在完全接种疫苗后，也建议继续使用非药物干预（例如，戴口罩）和替代疫苗策略（例如，额外剂量或免疫原性检测）。
IMPORTANCE Persons with immune dysfunction have a higher risk for severe COVID-19 outcomes. However, these patients were largely excluded from SARS-CoV-2 vaccine clinical trials, creating a large evidence gap.OBJECTIVE To identify the incidence rate and incidence rate ratio (IRR) for COVID-19 breakthrough infection after SARS-CoV-2 vaccination among persons with or without immune dysfunction.DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study analyzed data from the National COVID Cohort Collaborative (N3C), a partnership that developed a secure, centralized electronic medical record-based repository of COVID-19 clinical data from academic medical centers across the US. Persons who received at least 1 dose of a SARS-CoV-2 vaccine between December 10, 2020, and September 16, 2021, were included in the sample.MAIN OUTCOMES AND MEASURES Vaccination, COVID-19 diagnosis, immune dysfunction diagnoses (ie, HIV infection, multiple sclerosis, rheumatoid arthritis, solid organ transplant, and bone marrow transplantation), other comorbid conditions, and demographic data were accessed through the N3C Data Enclave. Breakthrough infection was defined as a COVID-19 infection that was contracted on or after the 14th day of vaccination, and the risk after full or partial vaccination was assessed for patients with or without immune dysfunction using Poisson regression with robust SEs. Poisson regression models were controlled for a study period (before or after [pre- or post-Delta variant] June 20, 2021), full vaccination status, COVID-19 infection before vaccination, demographic characteristics, geographic location, and comorbidity burden.RESULTS A total of 664 722 patients in the N3C sample were included. These patients had a median (IQR) age of 51 (34-66) years and were predominantly women (n = 378 307 [56.9%]). Overall, the incidence rate for COVID-19 breakthrough infection was 5.0 per 1000 person-months among fully vaccinated persons but was higher after the Delta variant became the dominant SARS-CoV-2 strain (incidence rate before vs after June 20, 2021, 2.2 [95% CI, 2.2-2.2] vs 7.3 [95% CI, 7.3-7.4] per 1000 person-months). Compared with partial vaccination, full vaccination was associated with a 28% reduced risk for breakthrough infection (adjusted IRR [AIRR], 0.72; 95% CI, 0.68-0.76). People with a breakthrough infection after full vaccination were more likely to be older and women. People with HIV infection (AIRR, 1.33; 95% CI, 1.18-1.49), rheumatoid arthritis (AIRR, 1.20; 95% CI, 1.09-1.32), and solid organ transplant (AIRR, 2.16; 95% CI, 1.96-2.38) had a higher rate of breakthrough infection.CONCLUSIONS AND RELEVANCE This cohort study found that full vaccination was associated with reduced risk of COVID-19 breakthrough infection, regardless of the immune status of patients. Despite full vaccination, persons with immune dysfunction had substantially higher risk for COVID-19 breakthrough infection than those without such a condition. For persons with immune dysfunction, continued use of nonpharmaceutical interventions (eg, mask wearing) and alternative vaccine strategies (eg, additional doses or immunogenicity testing) are recommended even after full vaccination.