Safety and reactogenicity of COVID-19 vaccines

The national rollout of COVID-19 vaccines has begun with the first several thousand doses already administered. This resource addresses the safety and reactogenicity (inflammatory reactions in response to vaccines) of COVID-19 vaccines


*ALERT* Evidence regarding COVID-19 is continually evolving. This resource will be updated regularly to reflect new emerging evidence but may not always include the very latest evidence in real-time.

To read or download a .PDF of the information contained in this article, please follow this link: ANMF COVID-19 Resources

Key points

  • Any vaccine used in Australia must be approved by the Therapeutic Goods Administration (TGA) as being safe and effective.
  • The Pfizer/BioNtech mRNA vaccine and the Oxford/AstraZeneca viral vector vaccines have provisional TGA approval in Australia.
  • Most reactions to the vaccines are local or systemic reactions to injection and foreign particles (reactogenicity) not a ‘mild’ form of COVID-19.
  • Mild-moderate local reactions include injection site pain and redness.
  • Mild-moderate systemic reactions include headache, tiredness, fever/chills, muscle aches.
  • Other less common mild-moderate reactions can include joint pain and nausea.
  • Most reactions disappear within a day or two.
  • Reports of serious reactions are rare, and most may not be to be related to the vaccine.
  • Allergic reactions and anaphylaxis are very uncommon and appear to be most common among people with a history of allergy or anaphylaxis related to either polyethylene glycol – PEG (an ingredient in the Pfizer/BioNTech vaccine), or polysorbate (an ingredient in the AstraZeneca vaccine).
  • The vaccines cannot cause COVID-19 infection.
  • The vaccines cannot change human DNA.

The Australian Government has detailed a national rollout strategy for the delivery of COVID-19 vaccines. In Phase 1a, vaccines will be available to quarantine and border workers, priority sub-groups of frontline health workers, and aged care and disability care staff and residents.1

COVID-19 vaccines have been developed to protect people against the ‘severe acute respiratory syndrome coronavirus 2’ virus (or ‘SARS-CoV-2’). Any COVID-19 vaccine approved for use in Australia may be effective in reducing the severity of illness but may not completely protect against infection or prevent a person from transmitting the virus to others. All current official recommendations regarding infection prevention and control should continue to be observed regardless of vaccine status.

Two vaccines have received provisional approval by the Australian Therapeutic Goods Administration (TGA) for administration in Australia; the Pfizer/BioNtech mRNA-based vaccine,2 and the Oxford/AstraZeneca viral vector vaccine.3 Only vaccines found to be safe and effective by the TGA are granted provisional registration. Safety and effectiveness is determined through analysis of ongoing clinical trials, international collaboration, and advice from the Advisory Committee on Vaccines (ACV). The TGA continually monitors the safety, quality, and efficacy of all vaccines before and following provisional approval.4,5  There are other COVID-19 vaccines under development at varying stages.6 Australia currently has agreements in place with four COVID-19 vaccine developers including the developers of the Novavax protein vaccine,7 and the  COVAX Facility that currently have nine different vaccines in varying stages of development under consideration, including the Moderna vaccine, an mRNA-based vaccine currently in use internationally.8,9,10 As the various vaccines are rolled out and administered around the world, many organisations and research studies are continuously monitoring their efficacy, safety, and impact upon COVID-19 outcomes and transmission.

This resource addresses the safety and reactogenicity (inflammatory reactions in response to vaccines) of COVID-19 vaccines. For evidence-based information about how the COVID-19 vaccines work please see the ANMF’s resource:

Reactions to approved COVID-19 vaccines

For both the Pfizer/BioNtech and AstraZeneca vaccines approved in Australia, most reactions are mild (i.e. do not interfere with daily activities) and only last a day or two. Moderate to severe reactions (such as headache, fever/chills, fatigue) are very uncommon and usually also resolve in two to three days.12,13 Severe reactions are very rare, but may be experienced by people with known allergies to certain ingredients of the vaccines.12,14

Mild-moderate reactions

The most common reactions to COVID-19 vaccines are the same as those people commonly experience for vaccines in general.12.15 These reactions are most often mild to moderate and can occur after both the first and second dose of a vaccine. Reactions can include:16

  • injection site pain and redness (within the first 24 hours)
  • headache
  • tiredness
  • fever/chills
  • muscle aches

Other less common reactions include joint pain and nausea.

Most reactions arise and then subside within a day or two of receiving the vaccine or occasionally up to a week. They generally do not interfere with the daily activities of most people. Commonly available pain relief medication, rest, and ensuring adequate hydration and comfortable body temperature is usually effective for reducing discomfort due to mild reactions to vaccination.12

If injection site pain or redness increases after 24 hours following vaccination, or other side effects do not dissipate after a few days, healthcare professional advice should be sought.12

Allergic reactions

Some people have experienced non-severe, immediate allergic reactions following COVID-19 vaccination.14 These reactions have presented within a few hours and include hives, swelling, and wheezing (respiratory distress). Severe allergic reactions (anaphylaxis) within minutes to hours are uncommon among people who have received COVID-19 vaccines.17,18

Allergic reactions to vaccines or their ingredients (e.g. polyethylene glycol – PEG) are rare. People who are known to be allergic to PEG (an ingredient in the Pfizer/BioNTech vaccine)19 or polysorbate (an ingredient in the AstraZeneca vaccine)20 should not receive a vaccine if it contains a known allergen.

It appears that unless a person has experienced an allergic reaction to the first dose of a COVID-19 vaccination or an ingredient known to be contained within the COVID-19 in question, it is likely that people who have a history of allergic reactions to other, non-COVID-19 vaccines or other sources can still be safely vaccinated.18 There is precedent for safely administering vaccines (for Yellow Fever) to people who are known to be allergic to vaccine ingredients (egg),21 and the suggestion that by identifying and effectively triaging people into groups who may require observation or skin-testing for allergic reactions to PEG and polysorbate, COVID-19 vaccines could be administered to people who are allergic.18

Reactions to specific vaccines

The Pfizer/BioNtech vaccine

Adverse reactions to the Pfizer/BioNtech vaccine are rare. By December 23, 2020 1,893,360 initial doses of the vaccine had been administered in the United States. Of these there were 4,393 (0.2%) adverse events submitted to the Vaccine Adverse Event Reporting System (VAERS). This included 175 case reports marked for further review as possible cases of severe allergic reaction. Of this group, anaphylaxis was identified as the cause of 21 cases of which 17 people had a history of allergies including 7 with a history of anaphylaxis.17

The Pfizer/BioNtech vaccine may cause mild-to-moderate, short-term pain at the injection site, headache, and fatigue.22 These reactions usually resolved within one to two days. Systemic reactions such as fever and chills may also be observed within the first one to two days following vaccination and usually resolve soon after.22

The incidence of other adverse events appears to be low; of 43,252 participants 64 vaccine recipients (0.3%) and six placebo recipients (<0.1%) reported lymph nodes swelling.22 Four vaccine related serious adverse events were reported from the 21,720 vaccine recipients; shoulder injury, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia.22

The Oxford/AstraZeneca vaccine

As for the Pfizer/BioNTech vaccine, mild-to-moderate, short-term reactions to the Oxford/AstraZeneca vaccine can occur. These are similarly unlikely to be related to the vaccine itself but are commonly occurring reactions to injections and foreign particles entering the body.

Studies that have investigated the efficacy and safety of the Oxford/AstraZeneca vaccine report few adverse events with similar profiles between experimental and control groups and few or none considered to be related to the vaccine.3,13

In one primary analysis of data from 11,636 participants in four large, ongoing randomised controlled trials in the United Kingdom, Brazil, and South Africa serious adverse events occurred in 168 participants including 79 (0.7%) who received the vaccine and 89 (0.8%) who received the meningococcal vaccine (MenACWY) or saline control.3 Adverse events of special interest (i.e. recorded but not classified as serious adverse events) occurred in 95 (0.8%) vaccine group participants and 126 (1.1%) control group participants. One case of fever >40C occurred two days following the first dose but resolved and did not occur again following the second dose. One case of idiopathic transverse myelitis (cause unknown) was reported in the vaccine group that may have been related to vaccination. All trial participants have recovered or are in a stable or improving condition.3

In another study, of 12,282 participants in the vaccine group 108 (0.9%) participants experienced a serious adverse event compared to 127 participants (1.1%) in the control group.23 Infections and infestations accounted for the largest number of serious adverse events in both experimental (23 participants) and control groups (41 participants). Reporting of serious adverse events included any serious adverse event including those that would be unrelated to vaccine administration (e.g. animal bite, road traffic accident).23

Other COVID-19 vaccine safety considerations

Approved COVID-19 vaccines don’t cause infection

While some vaccines for other illnesses use viruses that are weakened/attenuated (complete but genetically weakened) or inactivated and harmless (whole viruses, but ‘dead’ versions of the virus),24 the COVID-19 vaccines approved for use in Australia use only isolated parts of the SARS-CoV-2 virus (spike proteins) to generate an immune response and the production of antibodies.25 Because of this, the approved COVID-19 vaccines cannot infect a person with COVID-19.

The effectiveness of a person’s immune response to SARS-CoV-2 depends on the ability of their body to quickly recognise and respond to infection. When the immune system learns to recognise virus spike proteins, antibodies are developed to provide protection against infection.26

Approved COVID-19 vaccines don’t alter human DNA

COVID-19 vaccines that use deoxyribonucleic acid (DNA) such as the Oxford/AstraZeneca viral vector vaccine,3,13 or mRNA (messenger ribonucleic acid) including the Pfizer/BioNtech vaccine,27 and Moderna vaccine,28 have been found to be safe and effective.29,30

Other viral vector vaccines include those for Ebola, Hepatitis B, Human Papilloma Virus, and Whooping Cough.13 The genetic material in viral vector vaccines cannot integrate into human DNA in the cell nuclei, and only codes for the SARS-CoV-2 spike protein. Messenger RNA is different to the DNA that exits within chromosomes. Messenger RNA cannot combine with the DNA in cell nuclei to change the human genetic code and instead is broken down within the body’s cells within around 72 hours.31

Vaccines using mRNA technology have been in development for other viruses (e.g. Zika), but before now have not been used in practice.24,32 Vaccines contain the mRNA of a harmless SARS-CoV-2 spike protein responsible for binding the virus to human cells.22

References

  1. Australian Government Department of Health. Australia’s COVID-19 vaccine national roll-out strategy 2021. https://www.health.gov.au/resources/publications/australias-covid-19-vaccine-national-roll-out-strategy (accessed Feb 8 2021).
  2. Pfizer. Pfizer and BioNTech Announce Vaccine Candidate Against COVID-19 Achieved Success in First Interim Analysis from Phase 3 Study. Feb 9 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against (accessed Feb 16 2021).
  3. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet 2021; 397(10269): 99-111.
  4. Therapuetic Goods Administration. COVID-19 vaccines. 2021. https://www.tga.gov.au/covid-19-vaccines (accessed 8 Feb 2021).
  5. Australian Government Department of Health. Australian COVID-19 Vaccination Policy 2020. https://www.health.gov.au/resources/publications/australian-covid-19-vaccination-policy (accessed 8 Feb 2021).
  6. Forni G, Mantovani A, Forni G, et al. COVID-19 vaccines: where we stand and challenges ahead. Cell Death & Differentiation 2021; 28(2): 626-39.
  7. Mahase E. Covid-19: Novavax vaccine efficacy is 86% against UK variant and 60% against South African variant. BMJ 2021; 372: n296.
  8. European Center for Disease Prevention and Control. Overview of the implementation of COVID-19 vaccination strategies and vaccine deployment plans in the EU/EEA. 2021. https://www.ecdc.europa.eu/sites/default/files/documents/Overview-of-COVID-19-vaccination-strategies-deployment-plans-in-the-EU-EEA.pdf (accessed Feb 8 2021).
  9. Australian Government Department of Health. Australia’s vaccine agreements 2021. https://www.health.gov.au/initiatives-and-programs/covid-19-vaccines/about-covid-19-vaccines/australias-vaccine-agreements (accessed Feb 8 2021).
  10. Moderna. Moderna’s COVID-19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE Study. Feb 16 2021. https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy (accessed Feb 16 2021).
  11. Peters M, Marnie C. How do COVID-19 vaccines work? 19 Feb 2021 2021. https://anmf.org.au/pages/anmf-covid-19-resources (accessed 19 Feb 2021).
  12. Centers for Disease Control and Prevention (CDC). What to Expect after Getting a COVID-19 Vaccine. Feb 12 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/expect/after.html (accessed Feb 16 2021).
  13. Ramasamy MN, Minassian AM, Ewer KJ, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. The Lancet 2020; 396(10267): 1979-93.
  14. Centers for Disease Control and Prevention. COVID-19 Vaccines and Allergic Reactions. 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/allergic-reaction.html (accessed Feb 22 2021).
  15. Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how’s and what’s of vaccine reactogenicity. npj Vaccines 2019; 4(1): 39.
  16. Advisory Committee on Immunization Practices, Shimabukuro T. COVID-19 vaccine safety update. Jan 27 2021 (accessed Feb 22 2021).
  17. Shimabukuro T, Nair N. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine. JAMA 2021.
  18. Glover RE, Urquhart R, Lukawska J, Blumenthal KG. Vaccinating against covid-19 in people who report allergies. BMJ 2021; 372: n120.
  19. Therapuetic Goods Administration. AUSTRALIAN PRODUCT INFORMATION – COMIRNATY™ (BNT162b2 [mRNA]) COVID-19 VACCINE. 2021. https://www.tga.gov.au/covid-19-vaccine-pfizer-australia-comirnaty-bnt162b2-mrna (accessed Feb 22 2021).
  20. Therapuetic Goods Administration. AUSTRALIAN PRODUCT INFORMATION COVID-19 Vaccine AstraZeneca (ChAdOx1-S) solution for injection. 2021. https://www.tga.gov.au/sites/default/files/auspar-chadox1-s-covid-19-vaccine-astrazeneca-210215-pi.pdf (accessed Feb 22 2021).
  21. Sharma K, Perrett KP, Wood N. Yellow Fever Vaccination In EGG-Allergic Children. Pediatr Infect Dis J 2020; 39(6): e76-e8.
  22. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine 2020; 383(27): 2603-15.
  23. Voysey M, Costa Clemens SA, Madhi SA, et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. The Lancet 2021.
  24. Krammer F. SARS-CoV-2 vaccines in development. Nature 2020; 586(7830): 516-27.
  25. Walsh EE, Frenck RW, Falsey AR, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. New England Journal of Medicine 2020; 383(25): 2439-50.
  26. Sewell HF, Agius RM, Kendrick D, Stewart M. Covid-19 vaccines: delivering protective immunity. BMJ 2020; 371: m4838.
  27. Pfizer. Pfizer-BioNTech COVID-19 Vaccine U.S. Distribution Fact Sheet. 20 November 2020 2020. https://www.pfizer.com/news/hot-topics/covid_19_vaccine_u_s_distribution_fact_sheet (accessed Feb 16 2021).
  28. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. New England Journal of Medicine 2020; 384(5): 403-16.
  29. Jackson NAC, Kester KE, Casimiro D, Gurunathan S, DeRosa F. The promise of mRNA vaccines: a biotech and industrial perspective. npj Vaccines 2020; 5(1): 11.
  30. Silveira MM, Moreira GMSG, Mendonça M. DNA vaccines against COVID-19: Perspectives and challenges. Life Sciences 2021; 267: 118919.
  31. GAVI The Vaccine Alliance. Will an mRNA vaccine alter my DNA? 15 Dec 2020 2020. https://www.gavi.org/vaccineswork/will-mrna-vaccine-alter-my-dna (accessed 19 Feb 2021).
  32. Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics — developing a new class of drugs. Nature Reviews Drug Discovery 2014; 13(10): 759-80.

Authors
Micah D J Peters PhD and Mr Casey Marnie are in the National Policy Research Unit, Australian Nursing & Midwifery Federation (Federal Office).
Both are based at the University of South Australia, Clinical and Health Sciences, Rosemary Bryant AO Research Centre.

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