Drug hypersensitivity, in vitro tools, biomarkers, and burden with COVID-19 vaccines

Abstract

Hypersensitivity reactions to drugs are increasing worldwide. They display a large degree of variability in the immunological mechanisms involved, which impacts both disease severity and the optimal diagnostic procedure. Therefore, drug hypersensitivity diagnosis relies on both in vitro and in vivo assessments, although most of the methods are not well standardized. Moreover, several biomarkers can be used as valuable parameters for precision medicine that provide information on the endotypes, diagnosis, prognosis, and prediction of drug hypersensitivity development, as well on the identification of therapeutic targets and treatment efficacy monitoring. Furthermore, in the last 2 years, the SARS-CoV-2 (severe acute respiratory syndrome-coronavirus) pandemic has had an important impact on health system, leading us to update approaches on how to manage hypersensitivity reactions to drugs used for its treatment and on COVID-19 (Coronavirus disease) vaccines used for its prevention. This article reviews recent advances in these 3 areas regarding drug hypersensitivity: in vitro tools for drug hypersensitivity diagnosis, recently identified biomarkers that could guide clinical decision making and management of hypersensitivity reactions to drugs and vaccines used for COVID-19.

Keywords: COVID-19; biomarkers; hypersensitivity reactions; in vitro test; vaccines.

FIGURE 1

Global compilation of the three sections revised last time: (i) In vitro tools for the diagnosis of HSR to drugs, (ii) Biomarkers in HSR to drugs, and (iii) COVID‐19 pandemic. BAT, basophil activation test; HSR, hypersensitivity reactions; LTT, lymphocyte transformation test

FIGURE 2

In vitro tools for the diagnosis of HSR to drugs. (A) Representation of the novel in vitro immunoassays based on nanoparticles. Liposomes and silica nanoparticles decorated with antigenic determinants, the most used immunoassays for the diagnosis of HSRs, and scheme of the lymphocyte transformation test using dendritic cells (DC‐LTT) like drug presenting cells and of the proliferative response together with the schematic representation of the results based on the in vitro tool of T‐cell clonity. (B) Biomarkers in HSR to drugs. Biomarkers based on in vitro tests, total and specific IgE level, analysis of activation markers on basophils after stimulation with the specific drug, the proliferative response of effector cells and the measurement of specific cytokine levels by effector cells. In addition, the genetic variant can be also used as potential biomarkers, together with the analysis of soluble biomolecules in serum. CFSE, carboxyfluorescein diacetate N‐succinimidylester probe; GVHD; graft‐versus‐host disease; HSR, Hypersensitivity reactions

FIGURE 3

COVID‐19 vaccines. (A) Chronological representation from the pandemic declaration to the present, emphasizing the most relevant contributions associated with the diagnosis, management, and prevention of severe allergic reactions (anaphylaxis) to COVID‐19 vaccines. (B) Description of anti‐SARS‐CoV‐2 vaccines including the main allergenic‐containing excipients. The assessment for immediate reactions includes prick by prick with culprit vaccine, and prick test panel with excipients (pegylated, polysorbate 80, and PEG 2000) for diagnosis. Basophil activation test for Type‐1 reactions to PEG can be considered