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Hypersensitivity, diagnosis and Covid-19 vaccine

Palomares, Paris et al.

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

Allergy, European Academy of Allergy and Clinical Immunology (EAACI)

Wiley Online Library

First published: 01 August 2022


In this article researchers review advances in 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.


Their research shows that hypersensitivity reactions to drugs are increasing worldwide. Reactions display a constellation of symptoms ranging from urticaria to anaphylaxis or Stevens–Johnson syndrome/toxic epidermal necrolysis.


Diagnosis

The diagnosis of hypersensitivity to drugs is very complex and highly dependent on the mechanisms involved. A panel which combines tests in culture dishes (in vitro) and in people (in vivo) is recommended for an accurate diagnosis. Many of these methods are not well standardised and in order to improve their results, recent advances in in vitro tools have incorporated the application of nanoparticles for hypersensitivity to drug diagnosis.

In addition, previously known cellular tests have been deeply analysed and tuned up their techniques.


Biomarkers

Biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition.


Researchers note that new and promising molecules and mediators have been identified as the biomarkers for specific indications.

  1. Potential biomarker found in patients with a high risk of experience breakthrough reactions during drug desensitisation.

  2. They mention several other studies that have found a correlation between genetic factors and the development of hypersensitivity to drugs. However, there are limitations due to differences in the genetic background of different populations which hamper finding widely generalisable associations.

  3. Lastly, they discuss recently reported discovery - the use of serum soluble OX40 and how it could have significant value as both diagnosis and prognosis biomarker in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia (an increase in the number of a part of white blood cells in the blood) and systemic symptoms, observing that serum soluble OX40 levels were positively correlated with disease severity.


mRNA Covid-19 vaccines

The first vaccines approved were the mRNA vaccines by Pfizer/BioNTech (BNT162b2), Moderna (mRNA-1273), and the recombinant adenoviral (AZD1222 or ChAdOx1-S) by Oxford/AstraZeneca.


Cases of hypersensitivity after receiving the vaccine were reported few days after the vaccination-campaign started. This led to some health regulatory agencies to recommend not to have the vaccine to those with history of allergic reactions.


A potential cause of hypersensitivity to COVID-19 vaccines have been suggested to be polyethylene glycol (PEG). In other sudies PEG has been clearly demonstrated to cause hypersensitivity.


In addition to PEG, the role of other excipients such as polysorbate 80 as relevant allergens in vaccines remains more questionable. However, in case of severe reactions, excipients other than PEG should also be evaluated as causative agents.




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