Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study

Background: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. Objective: We assessed the frequency and risk factors of CU exacerbation and adverse reactions...

Full description

Autores:
Sánchez Caraballo, Jorge Marío
Giménez Arnau, Ana María
Kocaturk, Emek
Vera Ayala, Carolina E.
Criado, Paulo Ricardo
Tipo de recurso:
Article of investigation
Fecha de publicación:
2023
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/46816
Acceso en línea:
https://hdl.handle.net/10495/46816
Palabra clave:
Vacunas contra la COVID-19 - efectos adversos
COVID-19 Vaccines - adverse effects
COVID-19 - prevención y control
COVID-19 - prevention and control
Urticaria Crónica
Chronic Urticaria
Estudios Retrospectivos
Retrospective Studies
Urticaria - tratamiento farmacológico
Urticaria - drug therapy
Vacunación - efectos adversos
Vaccination - adverse effects
Brote de los Síntomas
Symptom Flare Up
Omalizumab
https://id.nlm.nih.gov/mesh/D000086663
https://id.nlm.nih.gov/mesh/D000086382
https://id.nlm.nih.gov/mesh/D000080223
https://id.nlm.nih.gov/mesh/D012189
https://id.nlm.nih.gov/mesh/D014581
https://id.nlm.nih.gov/mesh/D014611
https://id.nlm.nih.gov/mesh/D000067251
https://id.nlm.nih.gov/mesh/D000069444
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/4.0/
id UDEA2_93e423c80f182ff8af41d25c943555f6
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/46816
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.eng.fl_str_mv Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
title Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
spellingShingle Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
Vacunas contra la COVID-19 - efectos adversos
COVID-19 Vaccines - adverse effects
COVID-19 - prevención y control
COVID-19 - prevention and control
Urticaria Crónica
Chronic Urticaria
Estudios Retrospectivos
Retrospective Studies
Urticaria - tratamiento farmacológico
Urticaria - drug therapy
Vacunación - efectos adversos
Vaccination - adverse effects
Brote de los Síntomas
Symptom Flare Up
Omalizumab
https://id.nlm.nih.gov/mesh/D000086663
https://id.nlm.nih.gov/mesh/D000086382
https://id.nlm.nih.gov/mesh/D000080223
https://id.nlm.nih.gov/mesh/D012189
https://id.nlm.nih.gov/mesh/D014581
https://id.nlm.nih.gov/mesh/D014611
https://id.nlm.nih.gov/mesh/D000067251
https://id.nlm.nih.gov/mesh/D000069444
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
title_short Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
title_full Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
title_fullStr Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
title_full_unstemmed Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
title_sort Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
dc.creator.fl_str_mv Sánchez Caraballo, Jorge Marío
Giménez Arnau, Ana María
Kocaturk, Emek
Vera Ayala, Carolina E.
Criado, Paulo Ricardo
dc.contributor.author.none.fl_str_mv Sánchez Caraballo, Jorge Marío
Giménez Arnau, Ana María
Kocaturk, Emek
Vera Ayala, Carolina E.
Criado, Paulo Ricardo
dc.contributor.researchgroup.none.fl_str_mv Grupo de Alergología Clínica y Experimental (GACE)
dc.subject.decs.none.fl_str_mv Vacunas contra la COVID-19 - efectos adversos
COVID-19 Vaccines - adverse effects
COVID-19 - prevención y control
COVID-19 - prevention and control
Urticaria Crónica
Chronic Urticaria
Estudios Retrospectivos
Retrospective Studies
Urticaria - tratamiento farmacológico
Urticaria - drug therapy
Vacunación - efectos adversos
Vaccination - adverse effects
Brote de los Síntomas
Symptom Flare Up
Omalizumab
topic Vacunas contra la COVID-19 - efectos adversos
COVID-19 Vaccines - adverse effects
COVID-19 - prevención y control
COVID-19 - prevention and control
Urticaria Crónica
Chronic Urticaria
Estudios Retrospectivos
Retrospective Studies
Urticaria - tratamiento farmacológico
Urticaria - drug therapy
Vacunación - efectos adversos
Vaccination - adverse effects
Brote de los Síntomas
Symptom Flare Up
Omalizumab
https://id.nlm.nih.gov/mesh/D000086663
https://id.nlm.nih.gov/mesh/D000086382
https://id.nlm.nih.gov/mesh/D000080223
https://id.nlm.nih.gov/mesh/D012189
https://id.nlm.nih.gov/mesh/D014581
https://id.nlm.nih.gov/mesh/D014611
https://id.nlm.nih.gov/mesh/D000067251
https://id.nlm.nih.gov/mesh/D000069444
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D000086663
https://id.nlm.nih.gov/mesh/D000086382
https://id.nlm.nih.gov/mesh/D000080223
https://id.nlm.nih.gov/mesh/D012189
https://id.nlm.nih.gov/mesh/D014581
https://id.nlm.nih.gov/mesh/D014611
https://id.nlm.nih.gov/mesh/D000067251
https://id.nlm.nih.gov/mesh/D000069444
dc.subject.ods.none.fl_str_mv ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
description Background: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. Objective: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. Methods: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged >18 years and vaccinated with >1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. Results: Across 2769 COVID-19–vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination–induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination–induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine–related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. Conclusions: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated. (J Allergy Clin Immunol 2023;152:1095-106.)
publishDate 2023
dc.date.issued.none.fl_str_mv 2023
dc.date.accessioned.none.fl_str_mv 2025-07-20T23:32:31Z
dc.type.none.fl_str_mv Artículo de investigación
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dc.identifier.citation.none.fl_str_mv Kocatürk E, Salameh P, Sarac E, Vera Ayala CE, Thomsen SF, Zuberbier T, Ensina LF, Popov TA, van Doorn MBA, Giménez-Arnau AM, Asero R, Criado PR, Aarestrup FM, AbdulHameed Ansari Z, Al Abri S, Al-Ahmad M, Al Hinai B, Allenova A, Al-Nesf M, Altrichter S, Arnaout R, Bartosińska J, Bauer A, Bernstein JA, Bizjak M, Bonnekoh H, Bouillet L, Brzoza Z, Calvalcanti Dela Bianca Melo AC, Campinhos FL, Carne E, Purayil SC, Cherrez-Ojeda I, Chong-Neto HJ, Christoff G, Conlon N, Jardim Criado RF, Cvenkel K, Damadoglu E, Danilycheva I, Day C, de Montjoye L, Demir S, Ferucci SM, Fomina D, Fukunaga A, Garcia E, Gelincik A, Göbel JH, Godse K, Gonçalo M, Gotua M, Grattan C, Gugala A, Guillet C, Kalyoncu AF, Karakaya G, Kasperska-Zając A, Katelaris CH, Khoshkhui M, Kleinheinz A, Kolacinska-Flont M, Kolkhir P, Košnik M, Krasowska D, Kumaran MS, Kuprys-Lipinska I, Kurowski M, Kuznetsova EV, Larenas-Linnemann D, Lebedkina MS, Lee Y, Makris M, Gómez RM, Nasr I, Neisinger S, Oda Y, Kara RÖ, Palitot EB, Papapostolou N, Salvador Parisi CA, Pesque D, Peter J, Petkova E, Ridge K, Rudenko M, Rutkowski K, Saini SS, Salman A, Sanchez J, Şekerel B, Serdotetskova SA, Serpa FS, Dikicier BS, Sidiropoulos N, Sikora A, Sørensen JA, Soria A, Kucuk OS, Thalappil SR, Tomaszewska K, Tuncay G, Unal D, Valle S, van Lindonk E, Vestergaard C, Meshkova RY, Vitchuk A, Xepapadaki P, Ye YM, Zalewska-Janowska A, Zamlynski M, Maurer M. Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study. J Allergy Clin Immunol. 2023 Nov;152(5):1095-1106. doi: 10.1016/j.jaci.2023.07.019. Epub 2023 Aug 12. PMID: 37574079.
dc.identifier.issn.none.fl_str_mv 0091-6749
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/46816
dc.identifier.doi.none.fl_str_mv 10.1016/j.jaci.2023.07.019
dc.identifier.eissn.none.fl_str_mv 1097-6825
dc.identifier.pmid.none.fl_str_mv 37574079
identifier_str_mv Kocatürk E, Salameh P, Sarac E, Vera Ayala CE, Thomsen SF, Zuberbier T, Ensina LF, Popov TA, van Doorn MBA, Giménez-Arnau AM, Asero R, Criado PR, Aarestrup FM, AbdulHameed Ansari Z, Al Abri S, Al-Ahmad M, Al Hinai B, Allenova A, Al-Nesf M, Altrichter S, Arnaout R, Bartosińska J, Bauer A, Bernstein JA, Bizjak M, Bonnekoh H, Bouillet L, Brzoza Z, Calvalcanti Dela Bianca Melo AC, Campinhos FL, Carne E, Purayil SC, Cherrez-Ojeda I, Chong-Neto HJ, Christoff G, Conlon N, Jardim Criado RF, Cvenkel K, Damadoglu E, Danilycheva I, Day C, de Montjoye L, Demir S, Ferucci SM, Fomina D, Fukunaga A, Garcia E, Gelincik A, Göbel JH, Godse K, Gonçalo M, Gotua M, Grattan C, Gugala A, Guillet C, Kalyoncu AF, Karakaya G, Kasperska-Zając A, Katelaris CH, Khoshkhui M, Kleinheinz A, Kolacinska-Flont M, Kolkhir P, Košnik M, Krasowska D, Kumaran MS, Kuprys-Lipinska I, Kurowski M, Kuznetsova EV, Larenas-Linnemann D, Lebedkina MS, Lee Y, Makris M, Gómez RM, Nasr I, Neisinger S, Oda Y, Kara RÖ, Palitot EB, Papapostolou N, Salvador Parisi CA, Pesque D, Peter J, Petkova E, Ridge K, Rudenko M, Rutkowski K, Saini SS, Salman A, Sanchez J, Şekerel B, Serdotetskova SA, Serpa FS, Dikicier BS, Sidiropoulos N, Sikora A, Sørensen JA, Soria A, Kucuk OS, Thalappil SR, Tomaszewska K, Tuncay G, Unal D, Valle S, van Lindonk E, Vestergaard C, Meshkova RY, Vitchuk A, Xepapadaki P, Ye YM, Zalewska-Janowska A, Zamlynski M, Maurer M. Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study. J Allergy Clin Immunol. 2023 Nov;152(5):1095-1106. doi: 10.1016/j.jaci.2023.07.019. Epub 2023 Aug 12. PMID: 37574079.
0091-6749
10.1016/j.jaci.2023.07.019
1097-6825
37574079
url https://hdl.handle.net/10495/46816
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.none.fl_str_mv J. Allergy Clin. Immunol.
dc.relation.citationendpage.none.fl_str_mv 1106
dc.relation.citationissue.none.fl_str_mv 5
dc.relation.citationstartpage.none.fl_str_mv 1095
dc.relation.citationvolume.none.fl_str_mv 152
dc.relation.ispartofjournal.none.fl_str_mv Journal of Allergy and Clinical Immunology
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publisher.none.fl_str_mv Elsevier
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spelling Sánchez Caraballo, Jorge MaríoGiménez Arnau, Ana MaríaKocaturk, EmekVera Ayala, Carolina E.Criado, Paulo RicardoGrupo de Alergología Clínica y Experimental (GACE)2025-07-20T23:32:31Z2023Kocatürk E, Salameh P, Sarac E, Vera Ayala CE, Thomsen SF, Zuberbier T, Ensina LF, Popov TA, van Doorn MBA, Giménez-Arnau AM, Asero R, Criado PR, Aarestrup FM, AbdulHameed Ansari Z, Al Abri S, Al-Ahmad M, Al Hinai B, Allenova A, Al-Nesf M, Altrichter S, Arnaout R, Bartosińska J, Bauer A, Bernstein JA, Bizjak M, Bonnekoh H, Bouillet L, Brzoza Z, Calvalcanti Dela Bianca Melo AC, Campinhos FL, Carne E, Purayil SC, Cherrez-Ojeda I, Chong-Neto HJ, Christoff G, Conlon N, Jardim Criado RF, Cvenkel K, Damadoglu E, Danilycheva I, Day C, de Montjoye L, Demir S, Ferucci SM, Fomina D, Fukunaga A, Garcia E, Gelincik A, Göbel JH, Godse K, Gonçalo M, Gotua M, Grattan C, Gugala A, Guillet C, Kalyoncu AF, Karakaya G, Kasperska-Zając A, Katelaris CH, Khoshkhui M, Kleinheinz A, Kolacinska-Flont M, Kolkhir P, Košnik M, Krasowska D, Kumaran MS, Kuprys-Lipinska I, Kurowski M, Kuznetsova EV, Larenas-Linnemann D, Lebedkina MS, Lee Y, Makris M, Gómez RM, Nasr I, Neisinger S, Oda Y, Kara RÖ, Palitot EB, Papapostolou N, Salvador Parisi CA, Pesque D, Peter J, Petkova E, Ridge K, Rudenko M, Rutkowski K, Saini SS, Salman A, Sanchez J, Şekerel B, Serdotetskova SA, Serpa FS, Dikicier BS, Sidiropoulos N, Sikora A, Sørensen JA, Soria A, Kucuk OS, Thalappil SR, Tomaszewska K, Tuncay G, Unal D, Valle S, van Lindonk E, Vestergaard C, Meshkova RY, Vitchuk A, Xepapadaki P, Ye YM, Zalewska-Janowska A, Zamlynski M, Maurer M. Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study. J Allergy Clin Immunol. 2023 Nov;152(5):1095-1106. doi: 10.1016/j.jaci.2023.07.019. Epub 2023 Aug 12. PMID: 37574079.0091-6749https://hdl.handle.net/10495/4681610.1016/j.jaci.2023.07.0191097-682537574079Background: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. Objective: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. Methods: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged >18 years and vaccinated with >1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. Results: Across 2769 COVID-19–vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination–induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination–induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine–related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. Conclusions: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated. (J Allergy Clin Immunol 2023;152:1095-106.)COL005956712 páginasapplication/pdfengElsevierSan Luis, Estados Unidoshttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU studyArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/redcol/resource_type/ARTTexthttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionVacunas contra la COVID-19 - efectos adversosCOVID-19 Vaccines - adverse effectsCOVID-19 - prevención y controlCOVID-19 - prevention and controlUrticaria CrónicaChronic UrticariaEstudios RetrospectivosRetrospective StudiesUrticaria - tratamiento farmacológicoUrticaria - drug therapyVacunación - efectos adversosVaccination - adverse effectsBrote de los SíntomasSymptom Flare UpOmalizumabhttps://id.nlm.nih.gov/mesh/D000086663https://id.nlm.nih.gov/mesh/D000086382https://id.nlm.nih.gov/mesh/D000080223https://id.nlm.nih.gov/mesh/D012189https://id.nlm.nih.gov/mesh/D014581https://id.nlm.nih.gov/mesh/D014611https://id.nlm.nih.gov/mesh/D000067251https://id.nlm.nih.gov/mesh/D000069444ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edadesJ. Allergy Clin. 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