First infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risk of acute and postacute death and sequelae in various organ systems. Whether reinfection adds to risks incurred after first infection is unclear. Here we used the US Department of Veterans Affairs’ national healthcare database to build a cohort of individuals with one SARS-CoV-2 infection (n = 443,588), reinfection (two or more infections, n = 40,947) and a noninfected control (n = 5,334,729). We used inverse probability-weighted survival models to estimate risks and 6-month burdens of death, hospitalization and incident sequelae. Compared to no reinfection, reinfection contributed additional risks of death (hazard ratio (HR) = 2.17, 95% confidence intervals (CI) 1.93–2.45), hospitalization (HR = 3.32, 95% CI 3.13–3.51) and sequelae including pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders. The risks were evident regardless of vaccination status. The risks were most pronounced in the acute phase but persisted in the postacute phase at 6 months. Compared to noninfected controls, cumulative risks and burdens of repeat infection increased according to the number of infections. Limitations included a cohort of mostly white males. The evidence shows that reinfection further increases risks of death, hospitalization and sequelae in multiple organ systems in the acute and postacute phase. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.

首次感染严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 与各器官系统急性和急性后死亡及后遗症的风险增加相关。再次感染是否会增加首次感染后发生的风险尚不清楚。在这里，我们使用美国退伍军人事务部的国家医疗保健数据库建立了一组感染 1 次 SARS-CoV-2 的个体 ( n = 443,588)、再次感染的个体 (2 次或以上感染， n = 40,947) 和未感染的对照个体 ( n = 443,588)。 = 5,334,729）。我们使用逆概率加权生存模型来估计死亡、住院和事件后遗症的风险和 6 个月负担。与无再感染相比，再感染会带来额外的死亡风险（风险比 (HR) = 2.17，95% 置信区间 (CI) 1.93–2.45）、住院（HR = 3.32，95% CI 3.13–3.51）和后遗症，包括肺部、心血管、血液、糖尿病、胃肠道、肾脏、心理健康、肌肉骨骼和神经系统疾病。无论疫苗接种情况如何，风险都是显而易见的。这些风险在急性期最为明显，但在 6 个月的急性后期持续存在。与未感染的对照组相比，重复感染的累积风险和负担根据感染数量而增加。局限性包括一群主要是白人男性。证据表明，再感染进一步增加了急性期和急性期后多器官系统死亡、住院和后遗症的风险。减少 SARS-CoV-2 造成的死亡和疾病的总体负担需要采取预防再感染的策略。