Anaphylaxis post-COVID 19 mRNA vaccines

The Pfizer-BioNTech (Pfizer) and Moderna vaccines were authorised by the Health Sciences Authority (HSA) under the Pandemic Special Access Route (PSAR)1 on 14 December 2020 and 3 February 2021 for active immunisation to prevent COVID-19 caused by SARS-CoV-2 virus in individuals. With the use of the two mRNA vaccines internationally, rare reports of anaphylaxis, a severe life-threatening allergic reaction, started to be reported. Locally, HSA has received 58 adverse event (AE) reports from healthcare professionals on anaphylaxis which were adjudicated by its expert panel on hypersensitivity reactions based on the Brighton Collaboration Case Definition criteria.2 We would like to provide a brief update on these cases and the measures in place by HSA to mitigate the risk of anaphylaxis in individuals given the mRNA vaccines.

Anaphylaxis and its association with vaccines

Anaphylaxis is a rare and potentially life threatening generalised or systemic allergic or hypersensitivity reaction that can occur post-vaccination in certain susceptible individuals. It is a known AE associated with vaccines in general and reported to occur rarely in about 1 in 100,000 – 1 in 1 million doses administered. These severe allergic reactions should be distinguished from other events such as clinical manifestations that occur coincidental to vaccination (e.g. anxiety) and vasovagal responses.3

The interim authorisation of the mRNA vaccines under PSAR by HSA is based on ongoing clinical data provided by the company to support the continued positive benefit-risk balance of the vaccine for use in the COVID-19 pandemic.  While there were no imbalances of serious AEs detected in clinical trials between the vaccine and placebo arms of the mRNA vaccines, certain serious AEs, such as those of rare occurrence, may emerge when the vaccines are used in real world setting.

Adverse event reports of anaphylaxis with mRNA vaccines

The Pfizer vaccine has been in use since 30 December 2020 when Singapore started its national COVID-19 vaccination programme and the Moderna vaccine has been deployed for use on 12 March 2021. HSA has also granted approval for the use of the Pfizer vaccine in the 12 to 15 years age group on 18 May 2021, which was rolled out to students aged 12 years and above on 3 June 2021.

HSA has been closely monitoring the incidence of anaphylaxis associated with the mRNA vaccines. As the diagnosis of anaphylaxis can be subjective, HSA has convened an Expert Panel on Hypersensitivity reactions to adjudicate the reports. The Brighton Collaboration Case Definition criteria for anaphylaxis was applied in the adjudication of the cases as per international practice.2

As of 31 July 2021, 58 local AE reports were adjudicated to be anaphylaxis. The overall incidence of anaphylaxis with the mRNA vaccines is estimated to be 0.86 per 100,000 administered doses, which is similar to the incidence rate reported overseas. Forty-seven (81%) of these cases were reported with Pfizer vaccine and 11 with Moderna vaccine. Twenty-nine cases were assigned level 1 Brighton level of diagnostic certainty*, 28 as level 2 and the remaining one as level 3. Forty (69%) cases occurred with dose 1 and 18 cases occurred with dose 2 vaccination. Forty-eight of these 58 cases (83%) involved females. The median age of the 58 patients was 42 years (range: 16 to 76 years). Forty-one (71%) patients had a known history of atopy, allergies, or allergic reactions to drugs and/or foods. For most cases (66%), the interval from vaccination to onset of symptoms were within 30 minutes. Majority of the patients were treated with epinephrine as part of the management. Twenty-seven patients were hospitalised for observation and 30 were treated in the emergency department. All of the 58 patients have since recovered. Overview of the cases are presented in Table 1.

Table 1. Overview of the local cases of anaphylaxis post-vaccination with the mRNA vaccines from 30 December 2020 to 31 July 2021

Characteristics

No. (%) of cases

Pfizer-BioNTech and Moderna
(n=58)

Female

48 (83%)

Age in years, median (range)

 

42 (16-76)

 

History of atopy or allergies

41 (71%)

Symptom onset, min

  • ≤20min
  • ≤30min
  • >30min

 

  • 22 (38%)
  • 38 (66%)
  • 20 (34%)

Vaccine dose

  • First dose
  • Second dose

 

  • 40 (69%)
  • 18 (31%)

Anaphylaxis incidence rate (cases per 100,000 doses administered)

0.86

 

MOH and HSA’s actions and advisory

Several measures have been introduced to mitigate the risks of anaphylaxis with mRNA vaccines. They include:

  • Pre-vaccination screening prior to vaccination. Individuals with a history of allergic reaction or anaphylaxis to mRNA COVID-19 vaccine or any of its components are not recommended to receive the vaccine.
  • Observing individuals closely for 30 minutes after vaccination and giving post-vaccination advice to watch out for signs and symptoms of severe allergic reaction, and to seek immediate medical attention should they experience them.
  • Ensuring that all vaccination centres are medically equipped and staffed by qualified medical professionals at all times to provide medical treatment in the rare event that they are needed.

Healthcare professionals are required to report all suspected SAEs associated with COVID-19 vaccines to HSA. The reports will allow better computation of the frequency of AEs in Singapore and potentially in subgroups of individuals, for the monitoring of the safety of these vaccines to ensure that their benefits continue to outweigh their risks.

Healthcare professionals are encouraged to refer to the anaphylaxis guide at https://www.hsa.gov.sg/adverse-events/healthcare-professionals'-guide-to-adverse-events-reporting for reporting of anaphylaxis.

 

*There are 3 levels of diagnostic certainty: Brighton level 1 represents the highest level of diagnostic certainty that a reported case is indeed a case of anaphylaxis; levels 2 and 3 represent successively lower levels of diagnostic certainty.4

 

References

  1. https://www.hsa.gov.sg/therapeutic-products/register/special-access-routes/psar-emergency-therapeutic-product
  2. Vaccine 2007; 25(31):5675-84
  3. World Allergy Organ J. 2016; 9(1):32
  4. The Brighton Collaboration: Creating a Global Standard for Case Definitions (and Guidelines) for Adverse Events Following Immunization. In: Henriksen K, et al. Advances in Patient Safety: From Research to Implementation (Volume 2: Concepts and Methodology). Rockville (MD): Agency for Healthcare Research and Quality (US); 2005. Available from: https://www.ncbi.nlm.nih.gov/books/NBK20507/
Healthcare professional, Industry member, Therapeutic Products
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