Cutaneous adverse reactions following COVID‐19 vaccinations: A systematic review and meta‐analysis

Abstract

Background COVID‐19 vaccines are currently the most effective interventions in controlling and preventing severe disease progression. Dermatologic reactions to COVID‐19 vaccinations may be rare among clinical trial participants. However, since global mass vaccination became a reality, these adverse effects may become more widespread, and different skin reactions would arise. Objective To systematically review the cutaneous adverse reactions in cases subject to vaccines for COVID‐19. Methods We searched the PubMed, SCOPUS, Web of Science, and Embase databases, identifying the relevant records and including the eligible observational ones. After assessing the methodological quality of the included studies, we qualitatively and quantitatively synthesized the data regarding the cutaneous side effects experienced by those in the studies' population. Results Overall, 36 studies were included in our systematic review, with the majority being cross‐sectional. We found that pain, erythema, and swelling were the most common local side effects, while different types of rashes, urticaria, and angioedema were the most non‐local. Few cases also reported experiencing flare‐ups of their underlying diseases or developing newly‐onset diseases of various etiologies. Our meta‐analyses also found that while viral vector‐based vaccines are, though insignificantly, safer in injection site complaints, individuals who received mRNA vaccines developed significantly fewer non‐local cutaneous adverse events. Discussion Cutaneous reactions to the COVID‐19 vaccines are similar to common cutaneous drug eruptions and COVID‐19 cutaneous manifestations. However, we believe that further high‐quality research is needed to assess better how and why cutaneous reactions occur in different vaccines.

"Original Antigenic Sin" in SARS-CoV-2 Vaccination Followed by Infection

“…Whereas the Th17 role has been linked to an enhanced immune response producing eosinophilic pulmonary immunopathology in COVID-19 [ 9 ], the previous history of asthma and the vaccine adjuvant (aluminum-hydroxide) could have diminished these effects by polarizing into Th2 responses [ 4 , 9 ]. Eosinophilia was not verified during the first days, but IgE titers remained elevated five weeks after the onset of the symptoms.…”

“…Although an increase in the number of reports of skin manifestations has been documented in the context of SARS-CoV-2 infection and, more recently, after vaccination against COVID-19 [ 4 ], chance influence cannot be ruled out so we described these effects as adverse events, not reactions. The immunopathogenic mechanisms and the causal association can only be theorized, but the accumulated scientific evidence supports our suspicions.…”

“…Since massive vaccination has been implemented, reports of adverse events following approved vaccines have increased worldwide. The most frequent cutaneous effects reported are localized at the injection site [ 4 ], with a particular interest in the “COVID arm” phenomenon, a harmless delayed hypersensitivity reaction mostly related to mRNA vaccines [ 5 ] while those events classified as delayed local reactions typically start eight days or more after vaccination [ 4 ].…”

COVID‐19 vaccine and oral lesions: Putative pathogenic mechanisms

“…Although a cause-effect relationship has not been established yet, SARS-CoV-2 and COVID-19 vaccine-associated autoimmunity, resulting from molecular mimicry and immune cross-reactivity, has also been noticed with flare-ups of an underlying disease and new onsets in individuals susceptible to immune dysregulation. Anti-SARS-CoV-2 antibodies may cross-react with unknown aminoacidic sequences of glycoproteins on the host oral epitheliocytes, structurally similar to the viral ones (Shafie'ei et al, 2022), promoting autoreactive B or T lymphocytes activation, as previously hypothesized for antibodies targeting protein S in hepatitis B vaccines (Drago & Rebora, 2002). Alternatively, vaccines generated Spike proteins may bind angiotensin-converting enzyme-2 (ACE-2) receptors on oral epitheliocytes, recruiting CD4+ lymphocytes (Zengarini et al, 2022).…”

“…A further pathogenic hypothesis may be linked to the reactivation of herpes simplex virus type 1 and varicella‐zoster virus (Di Spirito, Amato, et al, 2022 ; Di Spirito, Pelella, et al, 2022 ; Shafie'ei et al, 2022 ), observed in oral mucosal and cutaneous adverse reactions. Both viruses are also involved in the genesis of erythema multiforme and Bell's palsy (Cirillo & Doan, 2022 ), the last seeming increasingly documented following mRNA and inactivated COVID‐19 vaccines compared with the background rate.…”