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 reac-tions 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%). Geographical-ly, different distribution patterns were observed for these reactions. Regard-ing 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 dif-ference among reactions between the first and the second dose of vaccines.Conclusions We examined the global incidence pattern of common cutane-ous reactions related to COVID-19 vaccination and found low incidence and short duration of systemic skin reactions and local injection site reactions (ex-cept 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.