核酸疫苗接種後因為新發自體免疫疾病及自體發炎疾病而導致的住院：單一中心觀察性研究

Hospitalizations for new-onset autoimmune and autoinflammatory diseases following vaccinations with nucleic acid-based vaccines: a single center experience

目的：自從新冠肺炎疫苗在全世界施打以來，核酸疫苗和免疫介導疾病之間是相關還是巧合的爭論持續至今。然而，新冠疫苗對重要臨床終點是否產生影響，目前仍缺乏流行病學證據。
方法：這篇研究回溯性地篩選自2021年4月至2022年3月，因為自體免疫疾病和自體發炎疾病活躍而在台北榮民總醫院住院的病人。這些病人大多被指派給風濕及免疫專科的主治醫師照顧。被招收到我們研究的141人之中，有38位患者符合資格，他們以新發自體免疫疾病及自體發炎疾病表現，而且在住院日前180天內接種AZD1222、BNT-162b2、或mRNA-1273新冠疫苗。我們的假說是接種疫苗之後所發生的住院非隨機發生，中間的潛伏期不呈均勻分布，並採用雙尾Kolmogorov-Smirnov適合度檢定進行分析。
結果：自前次接種疫苗至住院的潛伏期為平均53.8±31.1（人數38；中位數54.5）天。以Kolmogorov-Smirnov適合度檢定分析，潛伏期的分布並不是均勻的（p值為0.006）。接種疫苗後150天內沒有住院發生。180天觀察期內，31（81.6%）位病人集中於接種疫苗後75天內住院。
結論：核酸疫苗有可能引起免疫系統副作用，最終導致因為新發自體免疫疾病及自體發炎疾病而造成的住院，大多在疫苗接種後75天內發生。遇到相關臨床情境時應謹慎、留意。

Objective: Debates regarding association or coincidence between nucleic acid-based vaccines and immune-mediated diseases following their vaccinations have been ongoing since the introduction of COVID-19 vaccines worldwide. However, epidemiological evidence of their influences on hard clinical endpoints is still lacking.
Methods: We retrospectively screened medical charts for patients hospitalized to Taipei Veterans General Hospital (TVGH) for active autoimmune and autoinflammatory diseases between April 2021 and March 2022. They were mostly assigned to board-certified rheumatologists & immunologists in our hospital. Patients presenting with new-onset autoimmune and autoinflammatory diseases and receiving AZD1222, BNT-162b2, or mRNA-1273 within 180 days before the dates of admissions will be eligible. We hypothesized that hospitalizations following vaccinations are not random and the incubation periods would not distribute uniformly, assessed by two-tailed Kolmogorov-Smirnov test for goodness of fit.
Results: The incubation periods from the last vaccinations to admissions are, in average, 53.8±31.1 (N = 38; median 54.5) days. The distribution of the incubation periods was not uniform as analysed by Kolmogorov-Smirnov test (p = 0.006). There were no hospitalizations after 150 days post-vaccination, and admissions of 31 (81.6%) patients clustered within 75 days post-vaccination over a 180-day observation period.
Conclusions: Hospitalizations attributable to immunizations are rare events. Still, nucleic acid-based vaccines may potentially exert unwanted effects on the immune system of unfortunate individuals, leading to admissions for new-onset autoimmune/autoinflammatory diseases, mostly within 75 days postvaccination in our patients. Attention and cautions should be exercised among physicians upon relevant clinical scenarios.