Gray et al's investigation into angioedema–anaphylaxis deaths amidst the COVID-19 pandemic raises important forensic implications, particularly concerning differential diagnostics in postmortem settings (
1). However, a critical avenue requiring deeper contextualization is the immunopathological intersection between SARS-CoV-2-induced mast cell activation and bradykinin-mediated pathways (
2).
GrayAOuRDjabourianRAugustineJDSathyavagiswaranL. Deaths from angioedema–anaphylaxis and COVID-19. Acad Forensic Pathol. 2025;15(3):99–108. doi:10.1177/19253621251320212
2.
MarikPEIglesiasJVaronJKoryP. A scoping review of the pathophysiology of COVID-19. Int J Immunopathol Pharmacol. 2021;35(1):20587384211048026. doi: https://doi.org/10.1177/20587384211048026
3.
LimaHZhengJWongDWasermanSSussmanG. Pathophysiology of bradykinin and histamine mediated angioedema. Front Allergy. 2023:4(1):1263432. doi: https://doi.org/10.3389/falgy.2023.1263432
4.
LinRYSchwartzLBCurryA, et al.Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study. J Allergy Clin Immunol. 2000;106(1 Pt 1):65–71. doi: https://doi.org/10.1067/mai.2000.107600
5.
StammlerRDefendiFAubineauM, et al.Angioedema due to acquired C1-inhibitor deficiency without hematological condition: A multicenter French cohort study of 34 patients. J Allergy Clin Immunol Pract. 2025;13(3):542–550.e2. doi: https://doi.org/10.1016/j.jaip.2024.12.027
