This article was correct at time of publishing (February 11). For further news and updates please visit C+D’s COVID-19 hub
This article aims to help you answer any questions patients in the pharmacy may have regarding the latest advice about the COVID-19 vaccines.
COVID-19 vaccine: Delaying the second dose
What was the original guidance?
For both the Pfizer/BioNTech and the Oxford/AstraZenca vaccine, a two-dose schedule is advised. The original manufacturer information regarding the vaccines was to space the doses by at least three and four weeks respectively.(1,2) This information was updated on December 30, when the four chief medical officers in the UK and the Joint Committee on Vaccination and Immunisation (JCVI) advised that this interval should be increased to between three and 12 weeks for the Pfizer/BioNTech vaccine and four to 12 weeks for the Oxford/AstraZeneca vaccine, with a focus on administering the second dose towards the end of the 12-week period.
This was to allow more people to be given their first dose of a vaccine and the Medicines Healthcare products Regulatory Agency (MHRA) authorised this extended dose interval for both of the current vaccines.(3,4) There has been much debate in the press regarding this change in dosing interval.(4)
Why the change?
The change in dosing interval was introduced in an attempt to maximise the short-term impact of the vaccination programme, given data indicating high efficacy from the first dose of both vaccines. The committee advised that the delivery of the first dose to as many eligible individuals currently on the JCVI priority list as possible,(5) should be initially prioritised over delivery of a second dose. This is as a public health measure due to limited vaccine availability and the concern that many people in the UK at high risk of mortality or hospitalisation could be left with no protection at all.(3) This decision was taken in light of rapidly increasing transmission rates in December – due to more transmissible variants of the virus spreading rapidly across the UK.(3)
What is the evidence behind delaying the second dose?
The Oxford/AstraZenca vaccine
The latest information published as a preprint in The Lancet earlier this month (February 1), shows additional data from South Africa, Brazil and UK participants for the Oxford/AstraZenca vaccination trials.(6)
The study illustrates that:(6)
- There was 76% efficacy from day 22 to day 90 post vaccination in 17,177 trial participants after a single dose of the Oxford/AstraZenca vaccine.
- This efficacy did not decrease during the 12 weeks.
- There were no hospitalisations 22 days after a single dose.
- The efficacy was 82.4% after the second dose was administered at 12 weeks, and 54.9% if administered less than six weeks after the initial dose.
- The data also showed that there is evidence of a reduction in transmission of the virus to others.
The Pfizer/BioNTech vaccine
Pfizer has not collected much data regarding a period extending beyond three weeks before the administration of the second dose. Currently, the data shows that the Pfizer/BioNTech vaccine is 52% effective after a single dose and 95% effective after the second dose – based on the original 21-day interval between doses.(7)
The decision to increase the dose interval to a maximum of 12 weeks is based on the biology of the immune system and the assumption that the immune system will respond even if the second dose is delayed. However, there is a risk of infection in the time people are waiting for their delayed second dose due to the lower immune response in the early stages, as both doses are required for the 95% efficacy.(3)
What are the views on the increased dose interval?
- The JCVI, MHRA and four chief medical officers in the UK initiated this change.(3)
- AstraZeneca, as their latest data shows a better immune response with a longer gap.(6)
- The British Society for Immunology says that delaying the second dose by eight weeks is unlikely to have a detrimental impact on the overall immune response to the vaccine.(3)
- The World Health Organisation (WHO) have released interim recommendations (February 10) for the administration of the Oxford/AstraZeneca vaccine and has said that studies have shown an immunogenicity increase with a longer dose interval. It therefore recommends an interval of 8-12 weeks between the doses.(8)
- Pfizer and BioNTech released a joint statement advising against a change to the regimen as they have not completed the research for any extensions to the dose interval and are continuing to advise the three week interval as the optimal dosing.(3)
- For the Pfizer/BioNTech vaccine, based on advice provided by the Strategic Advisory Group of Experts on Immunisation (SAGE), the WHO agrees that some countries may need to increase the dose interval during “exceptional circumstances of vaccine supply constraints combined with a high disease burden” but recommends a gap of no longer than six weeks. This is based on the available trial data. The Pfizer/BioNTech vaccine had a maximum of 42 days between doses for some participants. This data illustrated a trend towards a substantial increase in antibody response following the second dose. Although WHO has initially suggested six weeks between doses, based on available data, they state that they will review this should more data for longer intervals become available.(9)
- The British Medical Association (BMA) has said it feels there is a need for a “proper scientific enquiry” to evaluate the decision to extend the interval between the first and second dose of the Pfizer/BioNTech vaccine beyond 42 days. This does not apply to the Oxford/AstraZeneca vaccine, as this “has got approval from its manufacturer for a delay of up to 12 weeks”, it said.(10)
Virus mutation and immunity
Pfizer has said it has no evidence that the protection of the first dose of its vaccine lasts beyond 21 days. People are advised to continue being cautious despite having had their first dose of COVID-19 vaccination.(3) This does not mean that the second dose will be less effective, but that patients may feel protected after their first dose and increase behaviour that may heighten the risk of transmission, such as not wearing face masks and not continuing to practice social distancing.
The most worrying risk is creating resistance to the vaccine by not providing full immune response in a short space of time. The virus is mutating and some of the new variants have much higher transmission rates and are slightly less responsive to the vaccine. However, according to a paper discussed by SAGE in January, the risks of resistance are considered small.(11)
There is a high likelihood that, over time, vaccine resistant variants will emerge. However, it is thought that this will be driven by increased population immunity due to natural infection rather than vaccine failure. This means that all vaccinated people who develop COVID-19 will need to undergo virus sequencing to keep ahead of any viral variations.(11)
Preliminary data published earlier this month (February 7) has shown that in a small study of approximately 2,000 volunteers, a two-dose regimen of the Oxford/AstraZeneca vaccine provides minimal protection against mild-moderate COVID-19 infection from the B.1.351 coronavirus variant first identified in South Africa.(12)
Pregnancy, breastfeeding and fertility
What was the original guidance?
At the start of the vaccination rollout, there was insufficient information to advise COVID-19 vaccine use in pregnancy or for breastfeeding women, or to know its effects on fertility. The advice from JCVI was to avoid it in all such cases, as it was felt the lack of evidence made it sensible to err on the side of caution.(13)
What is the updated guidance?
The JCVI published updated guidance on December 30, regarding the use of COVID-19 vaccines in pregnancy and breastfeeding. Although it does not recommend routine use in pregnancy, the guidance has been updated in light of the risks from the virus to those who are clinically extremely vulnerable or working on the frontline as health or social care workers.(14)
The JCVI advises that pregnant women should discuss the option of COVID-19 vaccination with either of the currently available vaccines with their obstetrician and/or doctor. Pharmacists can advise women who fall into a high risk category that the vaccine is not live and there are no known risks to administering non-live vaccines in pregnancy, as they cannot cause infection in either the woman or unborn child. Eligible candidates should still be advised that although there is no available information to indicate any safety concerns, there is insufficient evidence to recommend routine use.(14)
The advice has changed to allow the vaccine to be offered to breastfeeding mothers, if they are eligible and fall within one of the JCVI priority groups. The advice that there is a lack of safety data for use of the vaccines in breastfeeding remains, but there is currently no evidence to suggest any risks and women do not need to stop breastfeeding in order to receive the vaccination.(14)
In order to build this evidence, pregnant women who are eligible for the vaccine should be advised to receive this through their maternity unit or to ensure that it is reported via the maternity staff to the UK Obstetric Surveillance System/ UK Teratology Information Service vaccine registry.(14)
When advising women with specific reference to the Pfizer/BioNTech vaccine, you can reassure them that studies have shown that the mRNA vaccine does not affect fertility or cause any problems with pregnancy. It does not contain virus particles and the mRNA particles are eliminated within hours or days, so are unlikely to reach or cross the placenta. Immunity from vaccination in the mother can possibly keep the baby safe after birth.(15)
The Royal College of Obstetricians and Gynaecologists (RCOG) and the Royal College of Midwives (RCM) released statements last month (January 19) to clarify misinformation regarding the effect of the vaccines on fertility.(16)
They clarify that there is “no biologically plausible mechanism by which current vaccines would cause any impact on women’s fertility”. They also state that there is no evidence to support issues with fertility.(16)
Women considering pregnancy who are eligible for the vaccine - those who fall into the JCVI risk groups – should be encouraged to discuss any concerns they have with their midwife or healthcare professional, so they can make an informed decision about getting the vaccine.(16)
There are no known risks of the COVID-19 vaccines to male fertility either, and no known biological mechanisms for the virus to cause fertility issues in men. A study is being carried out to confirm this by reviewing sperm samples.(16) Other studies are looking at the effects on male fertility of contracting COVID-19 in light of the fact that there are known risks of general febrile illness causing inflammatory testicular issues for men and possible erectile dysfunction.(17) However, this has not been linked specifically to COVID-19 in large enough studies. Other factors, such as obesity, could also play a role in causing testicular inflammatory issues.(18) Pharmacists should reassure men of the benefits of the vaccine.
COVID-19 vaccination in people with allergies
What was the original guidance?
In early December, the MHRA advised that anyone with a history of anaphylaxis to vaccines, food or medicines would no longer be eligible to receive the vaccine, following the cases of two people who experienced anaphylaxis after receiving a dose of the Pfizer/BioNTech vaccine (the only vaccine available at the time).(19)
What is the updated guidance?
The Green Book chapter 14a has been updated – following the MHRA decision on December 30 – to state that anyone with a history of anaphylaxis to food, an identified drug or vaccine or an insect sting can receive any COVID-19 vaccine, as long as they are not known to be allergic to any excipient of the vaccine.(19) All recipients of the Pfizer/BioNTech COVID-19 vaccine should be kept for observation and monitored for a minimum of 15 minutes after receiving the vaccine. Facilities for management of anaphylaxis should be available at all vaccination sites.(20)
There is a reminder that the Pfizer/BioNTech vaccine contains polyethylene glycol (PEG) as an excipient, which can cause reactions in those who are sensitive to it. The Oxford/AstraZenca vaccine does not contain PEG, so may be offered as an alternative in this case. The Moderna vaccine is likely to carry the same warning as the Pfizer/BioNTech option, as it also contains PEG.(20)
Within the Green Book, the British Society for Allergy and Clinical Immunology has advised that if someone has a history of immediate onset anaphylaxis to multiple classes of drugs or any unexplained anaphylaxis, they should not receive the Pfizer/BioNTech vaccine, but should be offered the Oxford/AstraZenca vaccine if this is appropriate.(20)
If someone has a localised urticarial skin reaction (without systemic symptoms) after the first dose of their vaccine, they should receive their second dose, using an alternative vaccine, in a location with full resuscitation facilities – eg a hospital – with an extended 30-minute observation period.(20)
Those who have non-allergic reactions can receive the second dose of the same vaccine in any vaccination setting.(20)
The Specialist Pharmacy Service website has some clear information for pharmacists on advice to provide with regards to allergies and COVID-19 vaccines. This website also has further information regarding certification in specific religious communities, considerations regarding food, as well as specific information relating to ingredients such as PEG.(21)
Anticoagulants and pre-screening questionnaires
As part of the pre-screening questionnaire, people who are receiving the vaccine will be asked is they are taking anticoagulants or have blood clotting issues. Individuals on stable anticoagulant therapy, including those on warfarin whose INR is in the safe range, can receive the vaccine (assuming no other contraindications) although they may bruise at the site of vaccination. This question is asked so that vaccinators know to use a thinner needle and to apply an extended two-minute time of pressure after the vaccination, without rubbing, to reduce bleeding.(20,22)
The role of the pharmacist in providing consistent, evidence-based advice is critical to ensuring the appropriate uptake of the vaccine and to dispel any misinformation that can cause damage to the rollout of the essential COVID-19 vaccination programme.
Pharmacists can keep up to date with the latest information on COVID-19 vaccinations for healthcare professionals on the Gov.uk website.
- Gov.uk (2021) Information for healthcare professionals on Pfizer/BioNTech COVID-19 vaccine
- Gov.uk (2021) Information for healthcare professionals on COVID-19 vaccine AstraZeneca
- Iacobucci G, Mahase E. (2021) Covid-19 vaccination: What’s the evidence for extending the dosing interval? BMJ; 372:n18. doi: 10.1136/bmj.n18 pmid: 33408068
- Gov.uk (2020) Statement from the UK chief medical officers on the prioritisation of first doses of COVID-19 vaccines
- Gov.uk (2021) Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination, 30 December 2020
- Voysey, M, Costa C, Sue A et al. (2021) Oxford COVID vaccine trial, single dose administration, and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine. Preprints with the Lancet.
- Mahase E. (2020) Covid-19: Pfizer vaccine efficacy was 52% after first dose and 95% after second dose, paper shows. BMJ; 371:m4826. doi: 10.1136/bmj.m4826 pmid: 33310706 3
- World Health Organisation (2021) Interim recommendations for use of the AZD1222 (ChAdOx1-S (recombinant)) vaccine against COVID-19 developed by Oxford University and AstraZeneca
- World Health Organisation (2021) Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under emergency use listing
- Pulsetoday (2021) BMA calls for ‘dialogue’ with CMO about cutting 12-week vaccine interval
- Gov.uk (2021) SARS-CoV-2 immunity-escape variants, 7 January 2021
- University of Oxford (2021) ChAdOx1 nCov-19 provides minimal protection against mild-moderate COVID-19 infection from B.1.351 coronavirus variant in young South African adults
- Royal College of Obstetricians and Gynaecologists (2020) COVID-19 vaccination and pregnancy
- Royal College of Obstetricians and Gynaecologists (2020) Updated advice on COVID-19 vaccination in pregnancy and women who are breastfeeding
- Harvard Health Publishing (2021) Wondering about COVID-19 vaccines if you’re pregnant or breastfeeding?
- Royal College of Obstetricians and Gynaecologists (2021) The RCOG and the RCM respond to misinformation around COVID-19 vaccine and fertility
- Clinicaltrials.gov (2020) COVID-19 vaccine and impact on fertility study
- Tian, Yu, & Zhou, L. (2021) Evaluating the impact of COVID-19 on male reproduction. Reproduction, 161(2), R37-R44.
- Gov.uk (2020) Confirmation of guidance to vaccination centres on managing allergic reactions following COVID-19 vaccination with the Pfizer/BioNTech vaccine
- Public Health England (2021) The Green Book Immunisation against infectious disease. Chapter 14a: COVID-19 - SARS-CoV-2
- Specialist Pharmacy Services (2021) Advising individuals with allergies on their suitability for Pfizer-BioNTech COVID-19 vaccine
- Gov.uk (2021) COVID-19 vaccination programme: Information for healthcare practitioners.