Cardiac Arrhythmia after COVID-19 Vaccination versus Non–COVID-19 Vaccination: A Systematic Review and Meta-Analysis
Authors: Shi Ao , Tang Xiaoyi , Xia Panpan , Hao Meiqi , Shu Yuan , Nakanishi Hayato , Smayra Karen , Farzad Armin , Hu Kaibo , Liu Qi , Pan Su , Dixon Richard A. F. , Wu Yue , Cai Peng , Yu Peng , Li Pengyang 
Published: November 2022

Aims

Cardiac arrhythmia is a rare complication after vaccination. Recently, reports of arrhythmia after COVID-19 vaccination have increased. Whether the risk for cardiac arrhythmia is higher with COVID-19 vaccines than with non–COVID-19 vaccines remains controversial. This meta-analysis explored the incidence of arrhythmia after COVID-19 vaccination and compared it with the incidence of arrhythmia after non–COVID-19 vaccination.

Methods

We searched the MEDLINE, Scopus, Cochrane Library, and Embase databases for English-language studies reporting the incidence of arrhythmia (the primary endpoint) after vaccination from January 1, 1947 to October 28, 2022. Secondary endpoints included incidence of tachyarrhythmia and all-cause mortality. Subgroup analyses were conducted to evaluate the incidence of arrhythmia by age (children [<18 years] versus adults [≥18 years]), vaccine type (mRNA COVID-19 vaccine versus non-mRNA COVID-19 vaccine; individual non–COVID-19 vaccines versus COVID-19 vaccine), and COVID-19 vaccine dose (first versus second versus third). Random-effects meta-analyses were performed, and the intrastudy risk for bias and the certainty of evidence were evaluated. This study was registered with PROSPERO (CRD42022365912).

Results

The overall incidence of arrhythmia from 36 studies (1,528,459,662 vaccine doses) was 291.8 (95% CI 111.6-762.7) cases per million doses. The incidence of arrhythmia was significantly higher after COVID-19 vaccination (2263.4 [875.4-5839.2] cases per million doses; 830,585,553 doses, 23 studies) than after non–COVID-19 vaccination (9.9 [1.3-75.5] cases per million doses; 697,874,109 doses, 14 studies;P<0.01). Compared with COVID-19 vaccines, the influenza, pertussis, human papillomavirus, and acellular pertussis vaccines were associated with a significantly lower incidence of arrhythmia.

The incidence of tachyarrhythmia was significantly higher after COVID-19 vaccination (4367.5 [1535.2-12,360.8] cases per million doses; 1,208,656 doses, 15 studies) than after non– COVID-19 vaccination (25.8 [4.5-149.4] cases per million doses; 179,822,553 doses, 11 studies;P<0.01). Arrhythmia was also more frequent after the third dose of COVID-19 vaccine (19,064.3 [5775.5-61,051.2] cases per million doses; 7968 doses, 3 studies) than after the first dose (3450.9 [988.2-11,977.6] cases per million doses; 41,714,762 doses, 12 studies;P=0.05) or second dose (2262.5 [2205.9-2320.7] cases per million doses; 34,540,749 doses, 10 studies;P<0.01). All-cause mortality was comparable between the COVID-19 and non–COVID-19 vaccination groups.

Conclusions

The overall risk for arrhythmia after COVID-19 vaccination was relatively low, although it was higher in COVID-19 vaccine recipients than in non–COVID-19 vaccine recipients. This increased risk should be evaluated along with other important factors, such as the incidence of local outbreaks and the risk for arrhythmia due to COVID infection itself, when weighing the safety and efficacy of COVID-19 vaccines.