基于VAERS对两类不同COVID-19疫苗引起静脉血栓栓塞的风险信号分析

Risk signal analysis of venous thrombosis induced by two types of COVID-19 vaccines based on VAERS

目的:基于美国疫苗不良事件报告系统(Vaccine Adverse Event Reporting System,VAERS)数据,比较信使核糖核酸(messenger RNA,mRNA)、腺病毒载体两类COVID-19新冠疫苗引起静脉血栓栓塞(venous thromboembolism,VTE)不良事件的风险信号。方法:提取2020年1月至2023年6月VAERS数据库新冠疫苗相关不良反应(adverse drug reaction,ADR)数据,统计分析mRNA疫苗和腺病毒载体疫苗VTE不良反应的人口学特征;通过比例失衡法,利用报告比值比(reporting odds ratio,ROR)和Fisher’s精确检验检测比较两类新冠疫苗的VTE风险信号;使用Weibull分布分析两类新冠疫苗与VTE发病间隔的关系。结果:共检索到COVID-19疫苗VTE不良反应7764例,其中mRNA疫苗6445例,61~80岁人群发生VTE占比较高,以第2剂接种后发生VTE为主(2684例,41.64%);腺病毒载体疫苗1319例,VTE发生以第1剂接种后为主(843例,63.91%)。与其他疫苗相比,比例失衡法检测到两类新冠疫苗具有VTE风险信号,ROR分别为mRNA疫苗10.91(95%CI:8.07~14.76)和腺病毒载体疫苗29.63(95%CI:21.83~40.22)。同时,腺病毒载体疫苗与mRNA疫苗总VTE的ROR为2.71(95%CI:2.56~2.88),并检测到8个腺病毒载体疫苗VTE风险信号。Weibull分布结果显示3剂mRNA疫苗VTE距离接种的发生时间分别为9(3~23)d、23(5~83)d和25(6~107)d,2剂腺病毒载体疫苗VTE距离接种发生时间分别为17(8~46)d和16(5~182)d。结论:接种COVID-19新冠疫苗存在VTE风险,两类疫苗VTE均趋向于接种后早期出现。与mRNA疫苗相比,腺病毒载体疫苗存在较强的VTE风险信号,预防接种新冠疫苗时应注意监测VTE的发生。

OBJECTIVE To explore the trends in reporting venous thromboembolism(VTE)for two types of COVID-19 vaccinations based upon the data of Vaccine Adverse Event Reporting System(VAERS).METHODS Raw data on COVID-19 vaccines associated with adverse drug reactions(ADR)were retrieved from the database of VAERS from January 2020 to June 2023.Demographic profiles of messenger RNA(mRNA)vaccine and adenovirus vector-based vaccine associated with VTE were statistically examined.ADR signals of two types of vaccines were detected by reporting odds ratio(ROR)and Fisher's exact test and plotted on a volcano graph.Weibull distribution was utilized for time-to-onset analysis.RESULTS A total of 7764 cases of COVID-19 vaccines associated with VTE were retrieved,including mRNA vaccine(n=6445).A higher percentage of VTE occurred in 61-80-year-old subjects mostly after a second dose of vaccination(n=2684,41.64%).Among 1319 cases of adenovirus vector-based vaccine,VTE primarily occurred after an initial dose of immunization(n=843,63.91%).As compared with other vaccines,two types of COVID-19 vaccines carried the risk signals of VTE by proportional imbalance method with a ROR of 10.91(95%CI:8.07-14.76)for mRNA vaccine and 29.63(95%CI:21.83-40.22)for adenovirus vector-based vaccine.ROR for total VTE of adenovirus vector-based vaccine versus mRNA vaccine was 2.71(95%CI:2.56-2.88)and 8 risk signals of VTE were detected for adenovirus vector-based vaccine.Weibull distribution results indicated that VTE occurred at Day 9(3-23),23(5-83)and 25(6-107)post-vaccination for 3 doses of mRNA vaccine and Day 17(8-46)and 16(5-182)post-vaccination for 2 doses of adenovirus vector-based vaccine.CONCLUSION There is a risk of VTE associated with COVID-19 vaccination.And VTE is prone to occur during early post-vaccination period for both vaccines.As compared with mRNA vaccine,adenovirus-vectored vaccine has a stronger risk signal of VTE and VTE should be monitored during preventive COVID-19 vaccination.