Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants
Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants
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DOI：
10.1001/jama.2022.0470
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发表时间：
2022-01-21
影响因子：
120.7
通讯作者：
Verani, Jennifer R.
中科院分区：
文献类型：
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作者：
Accorsi, Emma K.;Britton, Amadea;Verani, Jennifer R.
重要性评估COVID-19疫苗对快速传播的SARS-CoV-2 Omicron变异株的性能对于提供公共卫生指导至关重要。目的评估接受3剂Pfizer-BioNTech BNT 162 b2或Moderna mRNA-1273疫苗与症状性SARS-CoV-2感染之间的相关性，按变异株分层（Omicron和Delta）.设计、设置和参与者在2021年12月10日至2022年1月1日期间对18岁或18岁以上的COVID样疾病成年人进行测试阴性病例对照分析，通过一个全国性的药物检测项目（美国49个州的4666个COVID-19检测点）。（第三次接种试验前>= 14天，第二次接种后>= 6个月）vs未接种疫苗，vs试验前6个月或更长时间接种2次疫苗主要结果和指标症状性SARS-CoV-2感染（根据使用S-基因靶失败定义的Omicron或Delta变体分层）和疫苗接种（3剂vs未接种和3剂vs 2剂）之间的相关性。相关性用多变量多项式回归进行测量。在这些病例中，次要结果是中位周期阈值（与存在的靶核酸的量成反比）的3种病毒基因，按变异和疫苗接种状态分层。（13 098 Omicron; 10 293 Delta）和46 764名对照（平均年龄，40.3 [SD，15.6]岁; 42 050 [60.1%]名女性）。18.6%报告既往接受过3剂mRNA疫苗（n = 2441）例Omicron病例，6.6%（n = 679）例Delta病例和39.7%对照组（n = 18 587）; 55.3%报告既往接受过2剂mRNA疫苗（n = 7245），44.4%（n = 4570），41.6%（n = 19 456）;未接种疫苗的报告率分别为26.0%（n = 3412）、49.0%（n = 5044）和18.6%（n = 8721）。3剂疫苗与未接种疫苗的调整后比值比为0.33（95% CI，0.31-0.35），Omicron和0.065 Delta（95% CI，0.059-0.071）;对于3剂疫苗与2剂疫苗，Omicron和Delta的校正比值比分别为0.34（95% CI，0.32-0.36）和0.16（95% CI，0.14-0.17）。对于Omicron和Delta，3次给药的病例中位周期阈值显著高于2次给药（Omicron N基因：19.35 vs 18.52; Omicron ORF 1ab基因：19.25 vs 18.40; Delta N基因：19.07 vs 17.52; Delta ORF 1ab基因：18.70 vs 17.28; Delta S基因：结论和相关性2021年12月在美国寻求COVID样疾病检测的个体中，与检测阴性对照相比，有症状的SARS-CoV-2感染病例接受3剂mRNA COVID-19疫苗（与未接种疫苗和接受2剂相比）的可能性较小。这些结果表明，接受3剂mRNA疫苗（相对于未接种疫苗和接受2剂）与针对Omicron和Delta变体的保护相关，尽管Omicron的优势比较高表明Omicron的保护作用低于Delta。
IMPORTANCE Assessing COVID-19 vaccine performance against the rapidly spreading SARS-CoV-2 Omicron variant is critical to inform public health guidance.OBJECTIVE To estimate the association between receipt of 3 doses of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccine and symptomatic SARS-CoV-2 infection, stratified by variant (Omicron and Delta).DESIGN, SETTING, AND PARTICIPANTS A test-negative case-control analysis among adults 18 years or older with COVID-like illness tested December 10, 2021, through January 1, 2022, by a national pharmacy-based testing program (4666 COVID-19 testing sites across 49 US states).EXPOSURES Three doses of mRNA COVID-19 vaccine (third dose >= 14 days before test and >= 6 months after second dose) vs unvaccinated and vs 2 doses 6 months or more before test (ie, eligible for a booster dose).MAIN OUTCOMES AND MEASURES Association between symptomatic SARS-CoV-2 infection (stratified by Omicron or Delta variants defined using S-gene target failure) and vaccination (3 doses vs unvaccinated and 3 doses vs 2 doses). Associations were measured with multivariable multinomial regression. Among cases, a secondary outcome was median cycle threshold values (inversely proportional to the amount of target nucleic acid present) for 3 viral genes, stratified by variant and vaccination status.RESULTS Overall, 23 391 cases (13 098 Omicron; 10 293 Delta) and 46 764 controls were included (mean age, 40.3 [SD, 15.6] years; 42 050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6%(n = 2441) of Omicron cases, 6.6%(n = 679) of Delta cases, and 39.7%(n = 18 587) of controls; prior receipt of 2 mRNA vaccine doses was reported for 55.3%(n = 7245), 44.4%(n = 4570), and 41.6%(n = 19 456), respectively; and being unvaccinated was reported for 26.0% (n = 3412), 49.0%(n = 5044), and 18.6% (n = 8721), respectively. The adjusted odds ratio for 3 doses vs unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta; for 3 vaccine doses vs 2 doses the adjusted odds ratio was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta. Median cycle threshold values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta (Omicron N gene: 19.35 vs 18.52; Omicron ORF1ab gene: 19.25 vs 18.40; Delta N gene: 19.07 vs 17.52; Delta ORF1ab gene: 18.70 vs 17.28; Delta S gene: 23.62 vs 20.24).CONCLUSIONS AND RELEVANCE Among individuals seeking testing for COVID-like illness in the US in December 2021, receipt of 3 doses of mRNA COVID-19 vaccine (compared with unvaccinated and with receipt of 2 doses) was less likely among cases with symptomatic SARS-CoV-2 infection compared with test-negative controls. These findings suggest that receipt of 3 doses of mRNA vaccine, relative to being unvaccinated and to receipt of 2 doses, was associated with protection against both the Omicron and Delta variants, although the higher odds ratios for Omicron suggest less protection for Omicron than for Delta.