The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders. The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.

已经描述了严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染（也称为 Long COVID）的急性后遗症，但接种疫苗的人中突破性的 SARS-CoV-2 感染 (BTI) 是否会导致后遗症- 急性后遗症尚不清楚。在这项研究中，我们使用美国退伍军人事务部国家医疗保健数据库建立了一个由 33,940 名 BTI 患者和几个没有 SARS-CoV-2 感染证据的人组成的队列，包括当代 ( n  = 4,983,491)、历史 ( n  = 5,785,273) 并接种疫苗 ( n = 2,566,369) 控制。在感染后 6 个月，我们发现，在疾病的前 30 天之后，与当代对照组相比，患有 BTI 的人表现出更高的死亡风险（风险比 (HR) = 1.75，95% 置信区间 (CI)：1.59 , 1.93) 和偶发的急性后遗症 (HR = 1.50, 95% CI: 1.46, 1.54)，包括心血管、凝血和血液、胃肠道、肾脏、心理健康、代谢、肌肉骨骼和神经系统疾病。与历史和接种疫苗的对照相比，结果是一致的。与之前未接种过疫苗的 SARS-CoV-2 感染者相比（n = 113,474)，BTI 患者的死亡风险较低 (HR = 0.66, 95% CI: 0.58, 0.74) 和急性后遗症 (HR = 0.85, 95% CI: 0.82, 0.89)。总之，研究结果表明，在感染前接种疫苗只能在疾病的急性后期阶段提供部分保护。因此，将其作为唯一的缓解策略可能无法最佳地减少 SARS-CoV-2 感染的长期健康后果。研究结果强调了继续优化 BTI 一级预防策略的必要性，并将指导 BTI 患者急性后护理途径的发展。