Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
ICES, Toronto, Ontario, Canada.
Clin Infect Dis. 2024 May 15;78(5):1372-1382. doi: 10.1093/cid/ciad716.
We assessed protection from coronavirus disease 2019 (COVID-19) vaccines and/or prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection against Omicron-associated severe outcomes during successive sublineage-predominant periods.
We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, polymerase chain reaction (PCR)-tested adults aged ≥50 years in Ontario, Canada, between 2 January 2022 and 30 June 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection.
We included 18 526 cases with Omicron-associated severe outcomes and 90 778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95% confidence interval [CI] 63%-72%; fourth-dose, 6-month: 80%, 95% CI 77%-83%) but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95% CI 48%-67%; 12-month: 49%, 95% CI 41%-56%; fourth-dose, 6-month: 62%, 95% CI 56%-68%, 12-months: 51%, 95% CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95% CI 36%-75%; fourth-dose, 6-month: 63%, 95% CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95% CI 79%-96%). Prior infection alone did not confer lasting protection.
Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.
我们评估了针对新型冠状病毒病 2019（COVID-19）疫苗和/或先前严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染对奥密克戎相关严重结局的保护作用，这些保护作用在连续的亚谱系主导期间发生。
我们使用了一种阴性病例对照设计，来评估 2022 年 1 月 2 日至 2023 年 6 月 30 日期间，安大略省社区居住、聚合酶链反应（PCR）检测的 50 岁及以上成年人中，疫苗和/或先前感染对住院/死亡的保护作用。多变量逻辑回归用于估计在最后一次接种或感染后 15 个月内，每剂（2-5 剂）疫苗和/或先前经 PCR 确诊的 SARS-CoV-2 感染（与未接种、未感染的受试者相比）对住院/死亡的几率的相对变化。
我们纳入了 18526 例奥密克戎相关严重结局病例和 90778 例阴性对照病例。在 BA.1/BA.2 主导期间，疫苗保护作用很高，但在 BA.4/BA.5 和 BQ/XBB 主导期间，保护作用通常<50%，且没有加强针。第三/第四剂疫苗在 BA.4/BA.5 主导期间短暂增加了保护作用（第三剂，6 个月：68%，95%置信区间[CI]63%-72%；第四剂，6 个月：80%，95% CI 77%-83%），但在 BQ/XBB 主导期间保护作用较低且迅速减弱（第三剂，6 个月：59%，95% CI 48%-67%；12 个月：49%，95% CI 41%-56%；第四剂，6 个月：62%，95% CI 56%-68%，12 个月：51%，95% CI 41%-56%）。混合免疫在 BA.1/BA.2 和 BA.4/BA.5 主导期间提供了近 90%的保护作用，但在 BQ/XBB 主导期间有所降低（第三剂，6 个月：60%，95% CI 36%-75%；第四剂，6 个月：63%，95% CI 42%-76%）。第五剂（二价）疫苗接种恢复了保护作用（6 个月：91%，95% CI 79%-96%）。单独的既往感染并不能提供持久的保护作用。
当免疫逃避变异/亚变体出现时，COVID-19 疫苗和/或先前 SARS-CoV-2 感染对严重结局的保护作用会降低，并且这种保护作用可能会随着时间的推移而减弱。我们的研究结果支持一种基于变异的加强针接种策略，并定期进行审查。
