PDF(Pubmed)
Abstract：
BACKGROUND: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines.
OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions.
METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements.
RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes.
CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.
OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions.
METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements.
RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes.
CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.
摘要：
背景：冠状病毒病-2019（COVID-19）mRNA疫苗后的系统性过敏反应（sAR）最初报道的发生率高于传统疫苗。
目的：我们的目的是评估这些个体重新接种疫苗的安全性，并询问这些反应的潜在机制。
方法：在本随机分组中，双盲,第二阶段试验，16-69岁的人，以前在他们的第一剂COVID-19mRNA疫苗中报告有令人信服的sAR，被随机分配到连续几天接受第二剂BNT162b2(Pfizer-BioNTech;Comirnaty®)疫苗和安慰剂，1：1在美国国立卫生研究院（NIH）的交叉时尚。五个月后,如果第二剂未导致严重的sAR,则提供开放标签的BNT162b2加强剂.在研究期间,没有参与者接受mRNA-1273(Moderna;Spikevax®)疫苗。主要终点是第二次给药和加强疫苗接种后sAR的复发;探索性终点包括生物标志物测量。
结果：在111名接受筛查的个体中，18人随机接受研究干预。八人接受BNT162b2第二剂，然后接受安慰剂；八人接受安慰剂，然后接受BNT162b2第二剂；两人在接受任何研究干预之前退出。所有16人都接受了加强剂量。在第二剂和加强疫苗接种后，sAR在两名受试者中复发(12.5%，95%CI1.6-38.3）。安慰剂后无sAR发生。模拟过敏反应，免疫应激相关反应(ISRR)，在接种疫苗和安慰剂后比sAR更常见，并且与更高的给药前焦虑评分相关，感觉异常,以及明显的生命体征和生物标志物变化。
结论：我们的研究结果支持对COVID-19mRNA疫苗报告sAR的个体进行重新接种。不同的临床和实验室特征可以区分sAR和ISRR。
目的：我们的目的是评估这些个体重新接种疫苗的安全性，并询问这些反应的潜在机制。
方法：在本随机分组中，双盲,第二阶段试验，16-69岁的人，以前在他们的第一剂COVID-19mRNA疫苗中报告有令人信服的sAR，被随机分配到连续几天接受第二剂BNT162b2(Pfizer-BioNTech;Comirnaty®)疫苗和安慰剂，1：1在美国国立卫生研究院（NIH）的交叉时尚。五个月后,如果第二剂未导致严重的sAR,则提供开放标签的BNT162b2加强剂.在研究期间,没有参与者接受mRNA-1273(Moderna;Spikevax®)疫苗。主要终点是第二次给药和加强疫苗接种后sAR的复发;探索性终点包括生物标志物测量。
结果：在111名接受筛查的个体中，18人随机接受研究干预。八人接受BNT162b2第二剂，然后接受安慰剂；八人接受安慰剂，然后接受BNT162b2第二剂；两人在接受任何研究干预之前退出。所有16人都接受了加强剂量。在第二剂和加强疫苗接种后，sAR在两名受试者中复发(12.5%，95%CI1.6-38.3）。安慰剂后无sAR发生。模拟过敏反应，免疫应激相关反应(ISRR)，在接种疫苗和安慰剂后比sAR更常见，并且与更高的给药前焦虑评分相关，感觉异常,以及明显的生命体征和生物标志物变化。
结论：我们的研究结果支持对COVID-19mRNA疫苗报告sAR的个体进行重新接种。不同的临床和实验室特征可以区分sAR和ISRR。
