Dermatological Complications of COVID 19 Vaccines: An Updated Review

Authors

  • Mohammed Omar Alsadi Primary Health Care Corporation, Doha, Qatar
  • Vinita John Primary Health Care Corporation, Doha, Qatar

DOI:

https://doi.org/10.55489/njcm.140320232663

Keywords:

DERMATOLOGICAL REACTIONS, SARS- COV-2, COVID 19, VACCINE

Abstract

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the 2019 coronavirus disease (COVID-19) pandemic, have been rapidly developed and authorized. However, recent studies showed that COVID-19 vaccination is associated with a wide range of dermatological reactions. The most prevalent adverse dermatological reaction observed in observational studies was a delayed large local reaction (DLRs), which is characterized by the appearance of an erythematous and edematous patch at the injection site four days or more after vaccination. Most of these reactions are common in females and resolve spontaneously within a few days to a weak. The second dose of the vaccine was associated with a higher incidence of cutaneous reactions compared to the first dose but milder in intensity. It seems that the Moderna vaccine is associated with a higher incidence of these adverse events compared to the Pfizer vaccine. Furthermore, mRNA vaccines had a higher incidence than vector-based and inactivated vaccines. There is a lack of evidence regarding the side events of the Johnson & Janssen vaccine. Further long-term, multicenter studies are required to compare these vaccines and highlight the best practice in managing these reactions.

References

Phelan AL, Katz R, Gostin LO. The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance. UNITEDSTATES.,JAMA.2020eb;323(8):709-10. Doi: https://doi.org/10.1001/jama.2020.1097 PMid:31999307

World Health Organization. Draft landscape of COVID‐19 candidate vaccines - 20 March 2020. 2020.

Chen Z, Zhang Y, Wang M, Islam MS, Liao P, Hu Y, et al. Humoral and Cellular Immune Responses of COVID-19 vaccines against SARS-Cov-2 Omicron variant: a systemic review. Int J Biol Sci. 2022;18(12):4629-41. Doi: https://doi.org/10.7150/ijbs.73583 PMid:35874952 PMCid:PMC9305266

Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20(10):615-32. Doi: https://doi.org/10.1038/s41577-020-00434-6 PMid:32887954 PMCid:PMC7472682

Kawasaki T, Kawai T. Toll-Like Receptor Signaling Pathways. Front Immunol.Sec.Cancer immunity and immunotherapy. 2014;5. Doi: https://doi.org/10.3389/fimmu.2014.00461 PMid:25309543 PMCid:PMC4174766

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 Feb;384(5):403-16. Doi: https://doi.org/10.1056/NEJMoa2035389 PMid:33378609 PMCid:PMC7787219

Català A, Muñoz-Santos C, Galván-Casas C, Roncero Riesco M, Revilla Nebreda D, Solá-Truyols A, et al. Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases. Br J Dermatol. 2022 Jan;186(1):142-52. Doi: https://doi.org/10.1111/bjd.20639 PMid:34254291 PMCid:PMC8444756

Tan SW, Tam YC, Oh CC. Skin manifestations of COVID-19: A worldwide review. JAAD Int. 2021 Mar;2:119-33. Doi: https://doi.org/10.1016/j.jdin.2020.12.003 PMid:33479703 PMCid:PMC7754879

Marzano AV, Genovese G, Moltrasio C, Gaspari V, Vezzoli P, Maione V, et al. The clinical spectrum of COVID-19-associated cutaneous manifestations: An Italian multicenter study of 200 adult patients. J Am Acad Dermatol. 2021 May;84(5):1356-63. Doi: https://doi.org/10.1016/j.jaad.2021.01.023 PMid:33476725 PMCid:PMC7816892

Genovese G, Moltrasio C, Berti E, Marzano AV. Skin Manifestations Associated with COVID-19: Current Knowledge and Future Perspectives. Dermatology. 2021;237(1):1-12. Doi: https://doi.org/10.1159/000512932 PMid:33232965 PMCid:PMC7801998

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med [Internet]. 2020 Dec 31 [cited 2022 Jun 19];383(27):2603-15. Doi: https://doi.org/10.1056/NEJMoa2034577 PMid:33301246 PMCid:PMC7745181

Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet (London, England). 2021 Dec;396(10267):1979-93.

Sadoff J, Le Gars M, Shukarev G, Heerwegh D, Truyers C, de Groot AM, et al. Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine. N Engl J Med. 2021 May;384(19):1824-35. Doi: https://doi.org/10.1056/NEJMoa2034201 PMid:33440088 PMCid:PMC7821985

Galván Casas C, Català A, Carretero Hernández G, Rodríguez‐Jiménez P, Fernández‐Nieto D, Rodríguez‐Villa Lario A, et al. Classification of the cutaneous manifestations of COVID ‐19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020 Jul;183(1):71-7. Doi: https://doi.org/10.1111/bjd.19163 PMid:32348545 PMCid:PMC7267236

Steber CR, Ponnatapura J, Hughes RT, Farris MK. Rapid Development of Clinically Symptomatic Radiation Recall Pneumonitis Immediately Following COVID-19 Vaccination. Vol. 13, Cureus. 2021. p. e14303. Doi: https://doi.org/10.7759/cureus.14303

Kounis NG, Koniari I, de Gregorio C, Velissaris D, Petalas K, Brinia A, et al. Allergic Reactions to Current Available COVID-19 Vaccinations: Pathophysiology, Causality, and Therapeutic Considerations. Vaccines [Internet]. 2021 [cited 2022 Aug 8];9(3):1-19. Available from: /pmc/articles/PMC7999280/ Doi: https://doi.org/10.3390/vaccines9030221 PMid:33807579 PMCid:PMC7999280

Niebel D, Novak N, Wilhelmi J, Ziob J, Wilsmann-Theis D, Bieber T, et al. Cutaneous Adverse Reactions to COVID-19 Vaccines: Insights from an Immuno-Dermatological Perspective. Vaccines. 2021 Aug;9(9). Doi: https://doi.org/10.3390/vaccines9090944 PMid:34579181 PMCid:PMC8470727

Dighriri IM, Alhusayni KM, Mobarki AY, Aljerary IS, Alqurashi KA, Aljuaid FA, et al. Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) Side Effects: A Systematic Review. Cureus. 2022 Mar;14(3):e23526. Doi: https://doi.org/10.7759/cureus.23526

McMahon DE, Amerson E, Rosenbach M, Lipoff JB, Moustafa D, Tyagi A, et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases. J Am Acad Dermatol. 2021;85(1):46-55. Doi: https://doi.org/10.1016/j.jaad.2021.03.092 PMid:33838206 PMCid:PMC8024548

Kroumpouzos G, Paroikaki ME, Yumeen S, Bhargava S, Mylonakis E. Cutaneous Complications of mRNA and AZD1222 COVID-19 Vaccines: A Worldwide Review. Microorganisms. 2022 Mar;10(3). Doi: https://doi.org/10.3390/microorganisms10030624 PMid:35336199 PMCid:PMC8953728

Vaccaro M, Bertino L, Squeri R, Genovese C, Isola S, Spatari G, et al. Early atypical injection-site reactions to COVID-19 vaccine: a case series. J Eur Acad Dermatology Venereol. 2022 Jan;36(1):e24-6. Doi: https://doi.org/10.1111/jdv.17683 PMid:34547113 PMCid:PMC8656410

Al Khames Aga QA, Alkhaffaf WH, Hatem TH, Nassir KF, Batineh Y, Dahham AT, et al. Safety of COVID-19 vaccines. J Med Virol. 2021 Dec;93(12):6588-94. Doi: https://doi.org/10.1002/jmv.27214 PMid:34270094 PMCid:PMC8426829

Abu-Hammad O, Alduraidi H, Abu-Hammad S, Alnazzawi A, Babkair H, Abu-Hammad A, et al. Side Effects Reported by Jordanian Healthcare Workers Who Received COVID-19 Vaccines. Vaccines. 2021 Jun;9(6). Doi: https://doi.org/10.3390/vaccines9060577 PMid:34205917 PMCid:PMC8228820

Han B, Song Y, Li C, Yang W, Ma Q, Jiang Z, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021 Dec;21(12):1645-53. Doi: https://doi.org/10.1016/S1473-3099(21)00319-4 PMid:34197764

Wu Z, Hu Y, Xu M, Chen Z, Yang W, Jiang Z, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021 Jun;21(6):803-12. Doi: https://doi.org/10.1016/S1473-3099(20)30987-7 PMid:33548194

Riad A, Sağıroğlu D, Üstün B, Pokorná A, Klugarová J, Attia S, et al. Prevalence and Risk Factors of CoronaVac Side Effects: An Independent Cross-Sectional Study among Healthcare Workers in Turkey. J Clin Med. 2021 Jun;10(12). Doi: https://doi.org/10.3390/jcm10122629 PMid:34203769 PMCid:PMC8232682

Bostan E, Yel B, Karaduman A. Cutaneous adverse events following 771 doses of the inactivated and mRNA COVID-19 vaccines: A survey study among health care providers. J Cosmet Dermatol. 2022 Sep;21(9):3682-8. Doi: https://doi.org/10.1111/jocd.15203 PMid:35775860 PMCid:PMC9350229

Cebeci Kahraman F, Savaş Erdoğan S, Aktaş ND, Albayrak H, Türkmen D, Borlu M, et al. Cutaneous reactions after COVID-19 vaccination in Turkey: A multicenter study. J Cosmet Dermatol. 2022 Sep;21(9):3692-703. Doi: https://doi.org/10.1111/jocd.15209 PMid:35780311 PMCid:PMC9349975

Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016 Oct;16(10):626-38. Doi: https://doi.org/10.1038/nri.2016.90 PMid:27546235

Zucker I, Prendergast BJ. Sex differences in pharmacokinetics predict adverse drug reactions in women. Biol Sex Differ. 2020 Jun;11(1):32. Doi: https://doi.org/10.1186/s13293-020-00308-5 PMid:32503637 PMCid:PMC7275616

Schwartz JB. The influence of sex on pharmacokinetics. Clin Pharmacokinet. 2003;42(2):107-21.eb 2003. Doi: https://doi.org/10.2165/00003088-200342020-00001 PMid:12537512

Elnaem MH, Mohd Taufek NH, Ab Rahman NS, Mohd Nazar NI, Zin CS, Nuffer W, et al. COVID-19 Vaccination Attitudes, Perceptions, and Side Effect Experiences in Malaysia: Do Age, Gender, and Vaccine Type Matter? Vaccines. 2021 Oct;9(10). Doi: https://doi.org/10.3390/vaccines9101156 PMid:34696264 PMCid:PMC8539146

Alhazmi A, Alamer E, Daws D, Hakami M, Darraj M, Abdelwahab S, et al. Evaluation of Side Effects Associated with COVID-19 Vaccines in Saudi Arabia. Vaccines. 2021 Jun;9(6). Doi: https://doi.org/10.3390/vaccines9060674 PMid:34207394 PMCid:PMC8235009

Centre for Disease Control (CDC). Interim Clinical Considerations for Use of COVID-19 Vaccines. 2022.

Blumenthal KG, Freeman EE, Saff RR, Robinson LB, Wolfson AR, Foreman RK, et al. Delayed Large Local Reactions to mRNA-1273 Vaccine against SARS-CoV-2. N Engl J Med [Internet]. 2021 Apr 1 [cited 2022 Jun 23];384(13):1273-7. Doi: https://doi.org/10.1056/NEJMc2102131 PMid:33657292 PMCid:PMC7944952

Blumenthal KG, Saff RR, Freeman EE. Delayed large local reactions to mRNA vaccines. Reply. N Engl J Med. 2021;384(24):e98. Doi: https://doi.org/10.1056/NEJMc2104751

Wei N, Fishman M, Wattenberg D, Gordon M, Lebwohl M. "COVID arm": A reaction to the Moderna vaccine. JAAD Case Reports. 2021;10:92-5. Doi: https://doi.org/10.1016/j.jdcr.2021.02.014 PMid:33748377 PMCid:PMC7959672

Fernandez-Nieto D, Hammerle J, Fernandez-Escribano M, Moreno-del Real CM, Garcia-Abellas P, Carretero-Barrio I, et al. Skin manifestations of the BNT162b2 mRNA COVID-19 vaccine in healthcare workers. "COVID-arm": a clinical and histological characterization. J Eur Acad Dermatol Venereol [Internet]. 2021 Jul 1 [cited 2022 Jun 24];35(7):e425-7. Doi: https://doi.org/10.1111/jdv.17250

Ramos CL, Kelso JM. "COVID Arm": Very delayed large injection site reactions to mRNA COVID-19 vaccines. J allergy Clin Immunol Pract. 2021 Jun;9(6):2480-1. Doi: https://doi.org/10.1016/j.jaip.2021.03.055 PMid:33864927 PMCid:PMC8056968

Sprute R, Schumacher S, Pauls M, Pauls W, Cornely OA. Delayed Cutaneous Hypersensitivity Reaction to Vaxzevria (ChAdOx1-S) Vaccine against SARS-CoV-2. Drugs R D. 2021 Dec;21(4):371-4. Doi: https://doi.org/10.1007/s40268-021-00358-z PMid:34351606 PMCid:PMC8339386

Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet (London, England). 2021 Jan;397(10269):99-111.

Fischinger S, Boudreau CM, Butler AL, Streeck H, Alter G. Sex differences in vaccine-induced humoral immunity. Semin Immunopathol. 2019;41(2):239-49. Doi: https://doi.org/10.1007/s00281-018-0726-5 PMid:30547182 PMCid:PMC6373179

Fink AL, Klein SL. Sex and Gender Impact Immune Responses to Vaccines Among the Elderly. Physiology. 2015 Nov;30(6):408-16. Doi: https://doi.org/10.1152/physiol.00035.2015 PMid:26525340 PMCid:PMC4630198

Fink AL, Klein SL. The evolution of greater humoral immunity in females than males: implications for vaccine efficacy. Curr Opin Physiol. 2018;6:16-20. Doi: https://doi.org/10.1016/j.cophys.2018.03.010 PMid:30320243 PMCid:PMC6181235

Flanagan KL, Fink AL, Plebanski M, Klein SL. Sex and Gender Differences in the Outcomes of Vaccination over the Life Course. Annu Rev Cell Dev Biol. 2017 Oct;33(1):577-99. Doi: https://doi.org/10.1146/annurev-cellbio-100616-060718 PMid:28992436

COVID CDC, Team R, Administration F and D. Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine-United States, December 14-23, 2020. Morb Mortal Wkly Rep. 2021;70(2):46. Doi: https://doi.org/10.15585/mmwr.mm7002e1 PMid:33444297 PMCid:PMC7808711

Ackerman M, Henry D, Finon A, Binois R, Esteve E. Persistent maculopapular rash after the first dose of Pfizer-BioNTech COVID-19 vaccine. Vol. 35, Journal of the European Academy of Dermatology and Venereology : JEADV. 2021. p. e423-5. Doi: https://doi.org/10.1111/jdv.17248 PMid:33783017 PMCid:PMC8250698

Jedlowski PM, Jedlowski MF. Morbilliform rash after administration of Pfizer-BioNTech COVID-19 mRNA vaccine. Dermatol Online J. 2021;27(1). Doi: https://doi.org/10.5070/D3271052044 PMid:33560802

Almutairi M, Azizalrahman A. Febrile morbilliform rash as a clinical presentation of COVID-19 in a pediatric patient. Int J Clin Pediatr. 2020;9(4):135-7. Doi: https://doi.org/10.14740/ijcp408

Najarian DJ. Morbilliform exanthem associated with COVID-19. JAAD Case Reports. 2020;6(6):493-4. Doi: https://doi.org/10.1016/j.jdcr.2020.04.015 PMid:32313826 PMCid:PMC7167547

Fattori A, Cribier B, Chenard MP, Mitcov M, Mayeur S, Weingertner N. Cutaneous manifestations in patients with coronavirus disease 2019: clinical and histological findings. Hum Pathol. 2021;107:39-45. Doi: https://doi.org/10.1016/j.humpath.2020.10.011 PMid:33161030 PMCid:PMC7834212

McNeil MM, DeStefano F. Vaccine-associated hypersensitivity. J Allergy Clin Immunol. 2018;141(2):463-72. Doi: https://doi.org/10.1016/j.jaci.2017.12.971 PMid:29413255 PMCid:PMC6602527

Park LHJ, Montgomery CJR, Boggs LNA. Anaphylaxis after the Covid-19 vaccine in a patient with cholinergic urticaria. Mil Med. 2021; Doi: https://doi.org/10.1093/milmed/usab138 PMid:33851711 PMCid:PMC8083203

Munavalli GG, Guthridge R, Knutsen-Larson S, Brodsky A, Matthew E, Landau M. "COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment". Arch Dermatol Res. 2022 Jan;314(1):1-15. Doi: https://doi.org/10.1007/s00403-021-02190-6 PMid:33559733 PMCid:PMC7871141

Munavalli GG, Knutsen-Larson S, Lupo MP, Geronemus RG. Oral angiotensin-converting enzyme inhibitors for treatment of delayed inflammatory reaction to dermal hyaluronic acid fillers following COVID-19 vaccination-a model for inhibition of angiotensin II-induced cutaneous inflammation. JAAD Case Reports. 2021;10:63-8. Doi: https://doi.org/10.1016/j.jdcr.2021.02.018 PMid:33681439 PMCid:PMC7923909

Rowland-Warmann MJ. Hypersensitivity reaction to Hyaluronic Acid Dermal filler following novel Coronavirus infection - a case report. J Cosmet Dermatol. 2021 May;20(5):1557-62. Doi: https://doi.org/10.1111/jocd.14074 PMid:33735503 PMCid:PMC8251125

Freeman EE, McMahon DE, Fox LP. Emerging Evidence of the Direct Association Between COVID-19 and Chilblains. JAMA dermatology. 2021 Feb;157(2):238-9. Doi: https://doi.org/10.1001/jamadermatol.2020.4937 PMid:33355601

Lopez S, Vakharia P, Vandergriff T, Freeman EE, Vasquez R. Pernio after COVID-19 vaccination. Vol. 185, The British journal of dermatology. 2021. p. 445-7. Doi: https://doi.org/10.1111/bjd.20404 PMid:33893637 PMCid:PMC8250679

Kha C, Itkin A. New-onset chilblains in close temporal association to mRNA-1273 vaccination. Vol. 12, JAAD case reports. 2021. p. 12-4. Doi: https://doi.org/10.1016/j.jdcr.2021.03.046 PMid:33898675 PMCid:PMC8057746

Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C, Takeshita J, et al. Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries. J Am Acad Dermatol. 2020 Aug;83(2):486-92. Doi: https://doi.org/10.1016/j.jaad.2020.05.109 PMid:32479979 PMCid:PMC7260509

Wollina U, Karadağ AS, Rowland-Payne C, Chiriac A, Lotti T. Cutaneous signs in COVID-19 patients: A review. Dermatol Ther. 2020 Sep;33(5):e13549. Doi: https://doi.org/10.1111/dth.13549

Herman A, Peeters C, Verroken A, Tromme I, Tennstedt D, Marot L, et al. Evaluation of Chilblains as a Manifestation of the COVID-19 Pandemic. JAMA dermatology. 2020 Sep;156(9):998-1003. Doi: https://doi.org/10.1001/jamadermatol.2020.2368 PMid:32584377 PMCid:PMC7317655

Gambichler T, Reuther J, Stücker M, Stranzenbach R, Torres-Reyes C, Schlottmann R, et al. SARS-CoV-2 spike protein is present in both endothelial and eccrine cells of a chilblain-like skin lesion. Vol. 35, Journal of the European Academy of Dermatology and Venereology : JEADV. 2021. p. e187-9. Doi: https://doi.org/10.1111/jdv.16970

Busto-Leis JM, Servera-Negre G, Mayor-Ibarguren A, Sendagorta-Cudós E, Feito-Rodríguez M, Nuño-González A, et al. Pityriasis rosea, COVID-19 and vaccination: new keys to understand an old acquaintance. Vol. 35, Journal of the European Academy of Dermatology and Venereology : JEADV. 2021. p. e489-91. Doi: https://doi.org/10.1111/jdv.17301 PMid:33899974 PMCid:PMC8242646

Malayala S V, Mohan G, Vasireddy D, Atluri P. Purpuric rash and thrombocytopenia after the mRNA-1273 (Moderna) COVID-19 vaccine. Cureus. 2021;13(3). Doi: https://doi.org/10.7759/cureus.14099

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2023-03-31

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Alsadi MO, John V. Dermatological Complications of COVID 19 Vaccines: An Updated Review. Natl J Community Med [Internet]. 2023 Mar. 31 [cited 2024 Nov. 23];14(03):180-6. Available from: https://njcmindia.com/index.php/file/article/view/2663

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Review Articles