Global incidence pattern and factors associated with common cutaneous reactions related to COVID-19 vaccination of 2.55 million participants in real-world settings: A systematic review and meta-analysis

BACKGROUND: Understanding the incidence pattern of cutaneous reactions is crucial for promoting COVID-19 vaccination. We aimed to report the global incidence pattern of, and factors associated with common cutaneous reactions related to COVID-19 vaccination in real-world settings. METHODS: We searched five databases (PubMed, Web of Science, Embase, CNKI, and Wanfang) from inception to May 13, 2022, for studies reporting the incidence of common cutaneous reactions related to COVID-19 vaccines in real-world settings. The outcomes were the systematic skin reactions (rash and urticaria) and the local injection site reactions (pain, swelling, redness, and erythema). We conducted random-effects meta-analyses and explored associated factors using multi-step statistical analyses. RESULTS: We included 35 studies and assessed 2 549 968 participants from 23 countries. The pooled incidence of overall systemic skin reactions was 3.8% (95% confidence interval (CI) = 2.4%-5.5%) with short duration (about one week). Specifically, the pooled incidence rates of rash and urticaria were 3.0% (95% CI = 2.1%-3.9%) and 1.1% (95% CI = 0.7%-1.5%), respectively. For overall local injection site reactions, the pooled incidence was 72.4% (95% CI = 65.7%-78.7%) with short duration (1 to 4.5 days). Except for local pain (72.2%, 95% CI = 65.3%-78.5%), other localized reactions had low incidence, including swelling (13.3%, 95% CI = 9.5%-17.7%), redness (11.5%, 95% CI = 5.7%-19.0%), and erythema (5.8%, 95% CI = 0.7%-15.4%). Geographically, different distribution patterns were observed for these reactions. Regarding associated factors, mRNA vaccines showed lower incidence of urticaria (P < 0.001). Asia population showed higher incidence of urticaria (P < 0.001). We observed lower incidence rates of overall local injection site reactions and pain among inactivated vaccines (P < 0.001). We found no significant difference among reactions between the first and the second dose of vaccines. CONCLUSIONS: We examined the global incidence pattern of common cutaneous reactions related to COVID-19 vaccination and found low incidence and short duration of systemic skin reactions and local injection site reactions (except for pain); discrepancies in these reactions were observed across different vaccine types. The cutaneous side effects related to COVID-19 vaccination do not seem to cause concern. REGISTRATION: PROSPERO: CRD42021258012.