COVID-19 infection is associated with an elevated risk for autoimmune blistering diseases while COVID-19 vaccination decreases the risk: A large-scale population-based cohort study of 112 million individuals

Philip Curman; Khalaf Kridin; Henner Zirpel; Gema Hernandez; Mehmet Akyuz; Diamant Thaci; Enno Schmidt; Ralf J Ludwig

doi:10.1016/j.jaad.2024.10.063

COVID-19 infection is associated with an elevated risk for autoimmune blistering diseases while COVID-19 vaccination decreases the risk: A large-scale population-based cohort study of 112 million individuals

J Am Acad Dermatol. 2024 Nov 7:S0190-9622(24)03111-6. doi: 10.1016/j.jaad.2024.10.063. Online ahead of print.

Authors

Philip Curman¹, Khalaf Kridin², Henner Zirpel³, Gema Hernandez⁴, Mehmet Akyuz⁵, Diamant Thaci³, Enno Schmidt⁶, Ralf J Ludwig⁷

Affiliations

¹ Dermato-Venereology Clinic, Karolinska University Hospital, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden; Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany. Electronic address: [email protected].
² Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel.
³ Institute and Comprehensive Centre for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany.
⁴ TriNetX, LLC, Cambridge, MA, USA and Biomedical Informatics Group, Artificial Intelligence Department, E.T.S.I. Informáticos, Universidad Politécnica de Madrid, Spain.
⁵ TriNetX Europe, Healthcare Partnerships, St. Martens-Latem, Belgium.
⁶ Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Lübeck, Lübeck, Germany.
⁷ Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Institute and Comprehensive Centre for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany; Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Lübeck, Lübeck, Germany.

PMID: 39521140
DOI: 10.1016/j.jaad.2024.10.063

Abstract

Background: Numerous diseases associated with COVID-19 infection and vaccination have been reported, including conditions such as the autoimmune blistering diseases (AIBD) pemphigus and pemphigoid. However, robust evidence supporting these associations is lacking.

Objective: To investigate the risk of developing AIBD following COVID-19 infection and vaccination.

Methods: Population-based retrospective cohort study utilizing data from over 112 million patients. The risk of AIBD within three months was compared among three cohorts: COVID-19 infection, COVID-19 vaccination, and controls, along with seven sensitivity analyses.

Results: COVID-19 infection was associated with an increased risk of AIBD (HR 1.508, 95% CI 1.260-1.805), with the risk being more pronounced for pemphigus (HR 2.432, 1.618-3.657) compared to bullous pemphigoid (HR 1.376, 1.019-1.857). Conversely, COVID-19 vaccination was associated with an almost halved risk of AIBD (HR 0.514, 0.394-0.672), with the risk reduction most significant for pemphigus (HR 0.477, 0.241-0.946). Comparisons between COVID-19 infection and vaccination revealed a more than threefold increased risk of AIBD in the infection cohort (HR 3.130, 2.411-4.063), particularly for pemphigus (HR 5.508, 2.973-10.205).

Limitations: Retrospective design and potential underreporting of COVID-19 cases and vaccinations.

Conclusion: COVID-19 infection significantly increases the risk of AIBD while vaccination appears to reduce this risk.

Keywords: Autoimmune disease; COVID-19 infection; COVID-19 vaccination; autoimmune blistering diseases; autoimmunity; pemphigoid; pemphigus; population-based cohort study.