Anaphylactic Reactions to COVID-19 Vaccines: An Updated Assessment Based on Pharmacovigilance Data.

This study aimed at producing an updated assessment of the incidence of anaphylaxis associated with COVID-19 vaccines based on pharmacovigilance data. Anaphylactic reaction and anaphylactic shock data post-COVID-19-vaccination reported from week 52, 2020 to week 1 or week 2, 2023 were collected from the VAERS and EudraVigilance databases, respectively, and analyzed comparatively. Incidence rates were calculated using the corresponding administered vaccine doses as denominators for all licensed vaccines and both platform types (mRNA or vectored). The latest data from the present analysis showed lower anaphylaxis incidence associated with COVID-19 vaccination compared to previous estimates from week 52, 2020 to week 39, 2021 (anaphylactic reaction: 8.96 (95% CI 8.80-9.11)/million doses overall (EEA: 14.19 (95% CI 13.92-14.47)/million/US: 3.17 (95% CI 3.03-3.31)/million); anaphylactic shock: 1.46 (95% CI 1.39-1.52)/million doses overall (EEA: 2.47 (95% CI 2.36-2.58)/million/US: 0.33 (95% CI 0.29-0.38)/million)). Incidence rates varied by vaccine and were higher as captured in EudraVigilance compared to the VAERS and for vectored compared to mRNA vaccines. Most reported cases had a favorable outcome. The extremely rare fatalities (overall rates across continents 0.04 (95% CI 0.03-0.06)/million doses for anaphylactic reaction and 0.02 (95% CI 0.01-0.03)/million vaccine doses for anaphylactic shock) were also associated with vector-rather than mRNA-based vaccines. The diminished incidence of anaphylaxis post-vaccination with COVID-19 vaccines offers assurance about their safety, as does the continuous potential adverse events monitoring through specialized pharmacovigilance databases.

Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products.

Polyethylene glycol (PEG) is a versatile polymer that is widely used as an additive in foods and cosmetics, and as a carrier in PEGylated therapeutics. Even though PEG is thought to be less immunogenic, or perhaps even non-immunogenic, with a variety of physicochemical properties, there is mounting evidence that PEG causes immunogenic responses when conjugated with other materials such as proteins and nanocarriers. Under these conditions, PEG with other materials can result in the production of anti-PEG antibodies after administration. The antibodies that are induced seem to have a deleterious impact on the therapeutic efficacy of subsequently administered PEGylated formulations. In addition, hypersensitivity to PEGylated formulations could be a significant barrier to the utility of PEGylated products. Several reports have linked the presence of anti-PEG antibodies to incidences of complement activation-related pseudoallergy (CARPA) following the administration of PEGylated formulations. The use of COVID-19 mRNA vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs), has recently gained wide acceptance, although many cases of post-vaccination hypersensitivity have been documented. Therefore, our review focuses not only on the importance of PEGs and its great role in improving the therapeutic efficacy of various medications, but also on the hypersensitivity reactions attributed to the use of PEGylated products that include PEG-based mRNA COVID-19 vaccines.

APPROACHING COVID-19 VACCINATION AND ANAPHYLAXIS FROM TWO DIRECTIONS

The SARS-COV-2 infection has already claimed the lives of more than 150 000 South Africans. In order to combat ongoing infections and fatalities, South Africa has commenced its largest adult mass vaccination roll-out ever. Roll-out commences against a backdrop of emerging science, increased anti-vaccine sentiments and much public anxiety about vaccine safety. Vaccine anaphylaxis is a serious adverse event known to occur in ~1 in a million doses with current registered vaccines. We discuss briefly the known epidemiology, diagnosis and common offending parts of vaccines that cause hypersensitivity. Similar to registered vaccines, anaphylaxis has been attributed to several COVID-19 vaccines, including a possible higher incidence up to ~8 in a million doses with the use of the novel mRNA COVID-19 vaccines. It is important that allergists approach both the risks and the management of COVID-19 vaccine-related anaphylaxis soundly. We present two recent cases to highlight our approach (i) to safe COVID-19 vaccination for patients with prior vaccine-related anaphylaxis, multiple-drug hypersensitivity syndrome or clonal mast-cell disorders;and (ii) to allergy work-up and the management of patients with COVID-19 vaccine-related allergy or anaphylaxis. In particular, we discuss administering a safe second dose if required for vaccine efficacy. © 2021, Allergy Society of South Africa. All rights reserved.

Do basophil activation tests help elucidate allergic reactions to the ingredients in COVID-19 vaccines?

The worldwide use of COVID-19 vaccines has shown that immediate allergic reactions to the ingredients are rare but should be clarified by means of an allergological work-up. This review aims to highlight the current state of knowledge and possible pathogenesis based on the literature published to date. In addition to recording a detailed history and performing skin tests, cellular tests (basophil activation or basophil histamine release test) by using the vaccines or modified compounds containing polyethylene glycol (PEG), rather than unmodified PEGs, have proven to be particularly helpful. Negative results with vaccines seem to indicate tolerance. Details of the performance of these cellular tests with different vaccines, PEGs of different molecular weights, other ingredients of the vaccines, as well as other PEGylated drugs, and the results in the context of COVID-19 vaccination of various working groups worldwide are summarized.

Selection of surrogate viruses for process control in detection of SARS-CoV-2 in wastewater.

Since SARS-CoV-2 RNA in wastewater is often present at low concentration or under detection limit, ensuring the reliability of detection processes using appropriate process controls is essential. The objective of this study was to evaluate applicability and limitations of candidate surrogate viruses as process controls under combinations of different virus concentration and RNA extraction methods. Detection efficiency of SARS-CoV-2 spiked in wastewater was compared with those of candidate surrogate viruses of bacteriophage ϕ6, pepper mild mottle virus (PMMoV), F-specific coliphage (F-phage), and murine norovirus (MNV). After inactivated SARS-CoV-2 and ϕ6 were spiked in two different wastewaters, the viruses in solid and liquid fractions of wastewater were concentrated by centrifuge and polyethylene glycol (PEG) precipitation, respectively. Viral RNA was extracted by using QIAamp Viral RNA Mini Kit and 3 other commercially available extraction kits, then quantified by reverse transcription-quantitative PCR using CDCN1 assay. Regardless of extraction kits, SARS-CoV-2 was consistently detected with good efficiency from both liquid (11-200%) and solid fractions (7.1-93%). Among the candidate process controls, PMMoV was widely detected at good efficiencies from both liquid and solid fractions regardless of selection of RNA extraction kits. F-phage and MNV also showed good detection efficiencies in most combinations of wastewater fractions and RNA extraction kits. An enveloped virus ɸ6 was found often undetected or to have very low detection efficiency (0.1-4.2%) even when SARS-CoV-2 spiked in wastewater was detected with good efficiency. Consequently, PMMoV is widely applicable as process control for detection of SARS-CoV-2 either in liquid fractions concentrated by PEG precipitation, or in solid fractions concentrated by centrifuge.

[ARN COVID-19 COMIRNATY Vaccine desensitization in a case of PEG Severe Immediate Hypersensitivity]. / Induction de tolérance au vaccin à ARN COMIRNATY chez un patient avec une hypersensibilité allergique sévère au PEG.

Vaccination is the most efficient way to fight the Covid epidemic. However, suspicion of severe hypersensitivity to PEG (PolyEthylen Glycol) usually constitutes a vaccine contraindication. We report the case of a patient with a proven allergy to PEG and skin sensitization to the COMIRNATY vaccine (PEG in its composition). He was able to benefit from the vaccine under the 5-step desensitization protocol. Conclusions: Specific allergological management should be offered to patients suspected of severe hypersensitivity to PEG and other vaccine excipients. We propose a solution for Comirnaty administration for patients with a proven severe allergy to PEG.