Wuller Shannon, Singer Nora G, Lewis Colby, Karlson Elizabeth W, Schulert Grant S, Goldman Jason D, Hadlock Jennifer, Arnold Jonathan, Hirabayashi Kathryn, Stiles Lauren E, Kleinman Lawrence C, Cowell Lindsay G, Hornig Mady, Hall Margaret A, Weiner Mark G, Koropsak Michael, Lamendola-Essel Michelle F, Kenney Rachel, Moffitt Richard A, Abedian Sajjad, Esquenazi-Karonika Shari, Johnson Steven G, Stroebel Stephenson, Wallace Zachary S, Costenbader Karen H
Department of Population Health, New York University Grossman School of Medicine, New York, New York, United States of America.
Department of Rheumatology, The MetroHealth System, Cleveland, Ohio, United States of America.
PLoS One. 2025 Jun 4;20(6):e0324513. doi: 10.1371/journal.pone.0324513. eCollection 2025.
SARS-CoV-2 infection has been associated with increased autoimmune disease risk. Past studies have not aligned regarding the most prevalent autoimmune diseases after infection, however. Furthermore, the relationship between infection severity and new autoimmune disease risk has not been well examined. We used RECOVER's electronic health record (EHR) networks, N3C, PCORnet, and PEDSnet, to estimate types and frequency of autoimmune diseases arising after SARS-CoV-2 infection and assessed how infection severity related to autoimmune disease risk. We identified patients of any age with SARS-CoV-2 infection between April 1, 2020 and April 1, 2021, and assigned them to a World Health Organization COVID-19 severity category for adults or the PEDSnet acute COVID-19 illness severity classification system for children (<age 21). We collected baseline covariates from the EHR in the year pre-index infection date and followed patients for 2 years for new autoimmune disease, defined as ≥ 2 new ICD-9, ICD-10, or SNOMED codes in the same concept set, starting >30 days after SARS-CoV-2 infection index date and occurring ≥1 day apart. We calculated overall and infection severity-stratified incidence ratesper 1000 person-years for all autoimmune diseases. With least severe COVID-19 severity as reference, survival analyses examined incident autoimmune disease risk. The most common new-onset autoimmune diseases in all networks were thyroid disease, psoriasis/psoriatic arthritis, and inflammatory bowel disease. Among adults, inflammatory arthritis was the most common, and Sjögren's disease also had high incidence. Incident type 1 diabetes and hematological autoimmune diseases were specifically found in children. Across networks, after adjustment, patients with highest COVID-19 severity had highest risk for new autoimmune disease vs. those with least severe disease (N3C: adjusted Hazard Ratio, (aHR) 1.47 (95%CI 1.33-1.66); PCORnet aHR 1.14 (95%CI 1.02-1.26); PEDSnet: aHR 3.14 (95%CI 2.42-4.07)]. Overall, severe acute COVID-19 was most strongly associated with autoimmune disease risk in three EHR networks.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染与自身免疫性疾病风险增加有关。然而，过去的研究对于感染后最常见的自身免疫性疾病并未达成一致。此外，感染严重程度与新发自身免疫性疾病风险之间的关系尚未得到充分研究。我们利用“恢复”（RECOVER）的电子健康记录（EHR）网络、国家COVID-19合作项目（N3C）、PCORnet和儿科电子数据网络（PEDSnet），来估计SARS-CoV-2感染后出现的自身免疫性疾病的类型和频率，并评估感染严重程度与自身免疫性疾病风险之间的关系。我们确定了2020年4月1日至2021年4月1日期间感染SARS-CoV-2的任何年龄患者，并将他们按照世界卫生组织针对成人的COVID-19严重程度分类或针对儿童（<21岁）的PEDSnet急性COVID-19疾病严重程度分类系统进行分类。我们在索引感染日期前一年从电子健康记录中收集基线协变量，并对患者随访2年，以观察新发自身免疫性疾病，新发自身免疫性疾病定义为在同一概念集中出现≥2个新的国际疾病分类第九版（ICD-9）、国际疾病分类第十版（ICD-10）或医学系统命名法（SNOMED）编码，在SARS-CoV-2感染索引日期后>30天开始出现且间隔≥1天。我们计算了所有自身免疫性疾病每1000人年的总体发病率和按感染严重程度分层的发病率。以最不严重的COVID-19严重程度为参照，生存分析检查了新发自身免疫性疾病的风险。所有网络中最常见的新发自身免疫性疾病是甲状腺疾病、银屑病/银屑病关节炎和炎症性肠病。在成人中，炎性关节炎最为常见，干燥综合征的发病率也很高。1型糖尿病和血液系统自身免疫性疾病在儿童中尤为常见。在所有网络中，经过调整后，与病情最不严重的患者相比，COVID-19严重程度最高的患者患新发自身免疫性疾病的风险最高（N3C：调整后风险比（aHR）1.47（95%置信区间1.33 - 1.66）；PCORnet aHR 1.14（95%置信区间1.02 - 1.26）；PEDSnet：aHR 3.14（95%置信区间2.42 - 4.07））。总体而言，在三个电子健康记录网络中严重急性COVID-19与自身免疫性疾病风险的关联最为强烈。
