Alhumaid Saad, Al Mutair Abbas, Al Alawi Zainab, Rabaan Ali A, Tirupathi Raghavendra, Alomari Mohammed A, Alshakhes Aqeel S, Alshawi Abeer M, Ahmed Gasmelseed Y, Almusabeh Hassan M, Alghareeb Tariq T, Alghuwainem Abdulaziz A, Alsulaiman Zainab A, Alabdulmuhsin Mohammed A, AlBuwaidi Emad A, Dukhi Amjad K Bu, Mufti Hani N, Al-Qahtani Manaf, Dhama Kuldeep, Al-Tawfiq Jaffar A, Al-Omari Awad
Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Ministry of Health, Rashdiah Street, P. O. Box 12944, Al-Ahsa, 31982, Saudi Arabia.
Research Center, Almoosa Specialist Hospital, Al-Ahsa, Saudi Arabia.
Allergy Asthma Clin Immunol. 2021 Oct 16;17(1):109. doi: 10.1186/s13223-021-00613-7.
Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population.
To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases.
A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed.
Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses.
Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I = 81%, p = < 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I = 99%, p = < 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I = 85% versus 2.8, 95% CI 0.0 to 5.7, I = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I = 99% versus 63.8, 95% CI 0.0 to 151.8, I = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger's tests confirmed asymmetry by producing p values < 0.05. Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. The key triggers to anaphylactic and nonanaphylactic reactions identified in these studies included foods, medications, stinging insects or jellyfish, contrast media, cosmetics and detergents, household products, and latex. Previous history of anaphylaxis; and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis and cholinergic urticaria were also found to be important.
The prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low; and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.
目前尚无关于普通成年人群中对SARS-CoV-2疫苗过敏反应和非过敏反应全球发病率的系统评价和荟萃分析。
估计COVID-19疫苗接种后过敏反应和非过敏反应的发病率，并描述确诊病例的人口统计学和临床特征、触发因素、表现出的体征和症状、治疗及临床过程。
一项系统评价和荟萃分析。遵循系统评价和荟萃分析的首选报告项目（PRISMA）声明。
于2020年12月1日至2021年5月31日使用以下关键词单独或组合在英文电子数据库（Proquest、Medline、Embase、Pubmed、CINAHL、Wiley在线图书馆和Nature）中进行检索：过敏反应、非过敏反应、过敏反应、非过敏反应、过敏性/类过敏性休克、超敏反应、过敏反应、变态反应、免疫反应、免疫性反应、血管性水肿、意识丧失、全身性红斑、荨麻疹、荨麻疹皮疹、发绀、呼噜声、喘鸣、呼吸急促、喘息、心动过速、腹痛、腹泻、恶心、呕吐和类胰蛋白酶。我们纳入了所有医疗机构中各年龄段成年人的研究。患病率的效应量合并为95%置信区间（CI）。为尽量减少异质性，我们进行了亚组分析。
在检索到的1734篇论文中，26篇文章纳入系统评价（8篇病例报告、5篇队列研究、4篇病例系列、2篇随机对照试验和1篇随机横断面研究），14篇文章（1篇队列研究、2篇病例系列、1篇随机对照试验和1篇随机横断面研究）纳入荟萃分析。分析了涉及26337421名疫苗接种者的研究[辉瑞-BioNTech（n = 14505399）和莫德纳（n = 11831488）]。两种疫苗过敏反应的总体合并患病率估计为5.0（95%CI 2.9至7.2，I = 81%，p = <0.0001），而两种疫苗非过敏反应的总体合并患病率估计为53.9（95%CI 0.0至116.1，I = 99%，p = <0.0001）。与莫德纳相比，接种辉瑞-BioNTech导致的过敏反应更高（8.0，95%CI 0.0至11.3，I = 85%，而莫德纳为2.8，95%CI 0.0至5.7，I = 59%）。然而，与莫德纳相比，辉瑞-BioNTech的非过敏反应发生率较低（43.9，95%CI 0.0至131.9，I = 99%，而莫德纳为63.8，95%CI 0.0至151.8，I = 98%）。基于mRNA疫苗类型确定与mRNA COVID-19免疫接种相关的过敏反应和非过敏反应发生率的合并效应量的可能发表偏倚的漏斗图在视觉检查时显得不对称，Egger检验通过产生p值<0.05证实了不对称性。在纳入的研究中，对SARS-CoV-2疫苗过敏反应和非过敏反应最常见的危险因素是女性和特应性个人史。这些研究中确定的过敏反应和非过敏反应的关键触发因素包括食物、药物、叮咬昆虫或水母、造影剂、化妆品和洗涤剂、家用产品以及乳胶。既往过敏反应史；以及哮喘、过敏性鼻炎、特应性和接触性湿疹/皮炎、银屑病和胆碱能性荨麻疹等合并症也被发现很重要。
COVID-19 mRNA疫苗相关过敏反应的患病率非常低；非过敏反应发生率较高，然而，皮肤反应大多为自限性。过敏反应和非过敏反应均不应阻碍疫苗接种。
