Overview

COVID-19 vaccines are being developed worldwide. All must be assessed as effective and meet strict safety standards before being used. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA), an independent authority, assess the safety, quality, and effectiveness of medicines.

UK Government initially prioritised COVID-19 vaccine for those considered at greatest risk, see: Priority groups for coronavirus (COVID-19) vaccination: advice from the Joint Committee on Vaccination and Immunisation (JCVI). The second phase of the UK immunisation programme was an age-based approach starting with the oldest adults first [1]. However, all adults aged 18 or over can now get vaccinated against COVID-19. Further information on the UK programme including how to get the vaccination, is available on the NHS website.

International travellers have not been identified as a priority group for COVID-19 vaccination but would be eligible for the vaccine if over 18 years or a child in a priority group. The current list of priority groups can be found in the Public Health England 'Green Book' COVID-19 chapter, tables 2 and 3. NaTHNaC is closely monitoring recommendations and will provide travel related updates as relevant.

Vaccines available in the UK

Most vaccines being developed use the spike (S)-protein on the virus surface as the target for antibodies that develop when the vaccine is administered to block the virus entering the cells and therefore expected to be protective against COVID-19 infection.

The following vaccines have been approved for use in the UK:

Pfizer BioNTech COVID-19 vaccine

This vaccine is a nucleoside-modified messenger RNA vaccine (mRNA). The genetic code (mRNA) from the SARS-CoV2 virus is used in the vaccine to enter cells of the person vaccinated to make the target S-protein stimulating the antibody response blocking viral entry into cells.

AstraZeneca COVID-19 vaccine

This vaccine uses a virus that does not cause illness, called a chimpanzee adenovirus (ChAD) to carry the genetic sequence of the SARS-COV S-protein into the cell of the person vaccinated to stimulate the antibody against the S-protein of the virus.

Moderna COVID-19 vaccine

This vaccine is a nucleoside-modified messenger RNA vaccine (mRNA). The genetic code (mRNA) from the SARS-CoV2 virus is used in the vaccine to enter cells of the person vaccinated to make the target S-protein stimulating the antibody response blocking viral entry into cells.

Janssen Ad26.COV2-S [recombinant] COVID-19 vaccine

This vaccine is made up of virus (from the adenovirus family) that has been modified to include DNA that codes for the S-protein on the SARS-CoV-2 virus. The vaccine stimulates an antibody response thereby blocking viral entry in to cells.

The vaccines are MHRA authorised and considered inactivated (including the non-replicating adenovirus vaccine) [1-3].

Note these vaccines are supplied in multidose vials

* For all the current UK approved vaccines, there is evidence of better immune response and/or protection where longer intervals between doses are used. Currently, JCVI is recommending a minimum interval of 8 weeks between doses of all the available COVID-19 vaccines [1, 4]. For those about to commence immunosuppressive treatment, the minimal intervals outlined in the table above may be followed to ensure that the vaccine is given whilst their immune system is better able to respond [1].

On 1 September 2021, the JCVI advised that a third primary dose is offered to those aged 12 years and over with severe immunosuppression around the time of their first or second dose. See criteria listed in Immunisation against infectious disease ‘the Green book’ COVID-19 chapter. Specialists should provide advice about the optimal timing for this third vaccine [1, 6].

** The JCVI advises that children and young people aged 12 years to 15 years with certain underlying health conditions should be offered a course of COVID-19 vaccine (see summary in Table 4 of Immunisation against infectious disease ‘the Green book’ COVID-19 chapter) [1]. The Pfizer BioNTech vaccine is preferred in this age group [1].

Children aged 12 years or older who live with an immunosuppressed person should also be offered a course of Pfizer BioNTech vaccine [1].

All 16- and 17-year-olds are recommended to receive a first dose of Pfizer BioNTech vaccine. The timing of the second dose in this age group is to be decided. Those turning 18 years in the next 3 months should be offered in accordance with recommendations for those aged 18 to 29 years [4].

On 13 September 2021, it was announced that all 12- to 15-year-olds will be offered a single dose of Pfizer/BioNTech COVID-19 vaccine. Children and young people aged 12 years and over who live with an immunosuppressed person and those in the clinical risk groups should be offered two doses of vaccine.

On 17 August 2021 MHRA authorised the use of Moderna vaccine in those aged 12 to 17 years of age. The JCVI decision on the use of Moderna vaccine in the UK vaccination programme is awaited.

*** Based on data on extremely rare adverse events following vaccination and current vaccine supply situation, JCVI are advising a preference for a vaccine other than AstraZeneca to be offered to healthy people under 40 years of age. Within this age group, those who are older (over 30 years of age), male, from certain minority ethnic backgrounds, in certain occupations at high risk of exposure, and those who are obese, remain at high risk of COVID-19. In the absence of a suitable alternative these individuals should still be offered the AstraZeneca vaccine, and may choose to receive the vaccine, provided they have been informed and understand the relative risks and benefits [1].

This advice is specific to the current UK context and may change if there is a change in the epidemiology or an interruption in the supply of the alternative vaccines [1,5].

**** Further details will be added when available in Immunisation against infectious disease Chapter 14a.

***** On 14 September 2021, the JCVI advised that booster vaccines are offered to those more at risk from serious disease, and who were vaccinated during Phase 1 of the vaccine programme in the UK. This includes those living in residential care homes for older adults, all adults aged 50 years or over, frontline health and social care workers, all those aged 16 to 49 years with underlying health conditions that put them at higher risk of severe COVID-19, and adult carers and adult household contacts of immunosuppressed individuals.

The second dose of vaccine should preferably be administered using the same vaccine used for the first dose, as higher rates of side effects have been reported after the second dose in mixed schedules. However, if the same vaccine is not available, it is considered reasonable to give a vaccine which is available, particularly if the individual is at immediate high risk of COVID-19 infection or considered unlikely to attend for vaccination again [1]. There are certain other situations in which it may be appropriate to give a different vaccine to the first, providing there are no contraindications. More information is available in COVID-19 vaccination programme: information for healthcare practitioners [4].

Whilst it is strongly advised that the second dose is given at the recommended interval, an inadvertent or unavoidable delay beyond the interval is unlikely to adversely affect the response to the second dose and longer-term protection. There is no need to restart the course and the second dose should be given as soon as can be arranged (preferably using the same vaccine to complete the course). Timely administration is still encouraged to significantly boost protection and prevent further hospitalisations and deaths [4].

Based on current information about these COVID-19 vaccines, there is little evidence of safety concerns with co-administration with other inactivated vaccines, although attribution of any adverse effects may be more difficult. As the current COVID-19 vaccines in the UK are considered inactivated, where individuals in an eligible cohort present having received another inactivated or live vaccine, COVID-19 vaccination should still be given. The same applies for other live and inactivated vaccines where COVID-19 vaccination has been received first or where a patient presents requiring two vaccines. It is generally better for vaccination to proceed to avoid any further delay in protection and to avoid the risk of the patient not returning for a later appointment. An exception to this is shingles vaccination, where ideally a 7-day interval should be observed as there is potential for an inflammatory response following COVID-19 vaccine to reduce the response to the live virus shingles vaccine [1].

More information about the use of COVID-19 vaccines for those with special health needs including during pregnancy, breastfeeding and those who are immunosuppressed or have HIV infection is available in Immunisation against infectious disease Chapter 14a.

Contraindications and precautions to COVID-19 vaccination

There are very few individuals who cannot receive the Pfizer-BioNTech, AstraZeneca or Moderna COVID-19 vaccines. Information on the Janssen vaccine will be updated once published.

Contraindications:

The following are relative contraindications:
Confirmed previous systemic allergic reaction (including immediate-onset anaphylaxis) to:

• a previous dose of the same COVID-19 vaccine [see also Adverse Reactions]
• any components of the vaccine e.g. polyethylene glycol

Polyethylene glycol (PEG) is present in the mRNA vaccines from Pfizer-BioNTech and Moderna [1]. Known allergy to PEG (present in some medicines, household goods and cosmetics) is rare. Published data now show that some individuals with prior allergic reaction to PEG containing medicines can tolerate the PfizerBioNTech vaccine (although the historical reaction may have been due a non-PEG component) [1]. Expert advice should be obtained and if a decision is made to administer an mRNA vaccine, then this should only be done in hospital under medical supervision [1]. A link to guidance for children with cancer who may be receiving PEG containing drugs is available in Immunisation against infectious disease, COVID-19 chapter.

Some individuals are allergic to polysorbate 80 widely used in medicines, foods and some medicines including some injected influenza vaccines. Individuals with known allergy to polysorbate 80 should not receive the AstraZeneca vaccine.

The British Society for Allergy and Clinical Immunology (BSACI) has advised that individuals who have a reaction to the first dose of a COVID-19 vaccine may be able to receive a second dose. For further details see flow chart for managing patients who have allergic reactions to the first dose.

The MHRA has also undertaken a review into UK reports of very rare blood clots together with low levels of platelets (thrombocytopenia) following vaccination with the AstraZeneca COVID-19 vaccine. The following are considered contraindications for receiving the AstraZeneca COVID vaccine and these individuals may be offered an alternative COVID-19 vaccine:

• A history of cerebral or other major blood clots occurring with low levels of platelets after their first vaccine dose of the AstraZeneca COVID-19 vaccine.
• A history of heparin-induced thrombocytopaenia and thrombosis (HITT or HIT type 2) [7].

A history of thrombosis without low platelet levels including antiphospholipid syndrome is not a contraindication to AstraZeneca COVID-19 vaccine [1].

Extremely rare reports of capillary leak syndrome have been reported after AstraZeneca Vaccine. Individuals with a prior history of this condition may be offered an alternative COVID-19 vaccine [1].

COVID-19 vaccine guidance is subject to regular revisions, check up to date guidance for health practitioners on GOV.UK.

Precautions:

If acutely unwell, postpone until fully recovered.

Vaccination of individuals who may be infected or asymptomatic or incubating COVID-19 infection is unlikely to have a detrimental effect on the illness. However, vaccination should be deferred in those with confirmed infection to avoid confusing the differential diagnosis. As clinical deterioration can occur up to two weeks after infection, ideally vaccination should be deferred until clinical recovery to around four weeks after onset of symptoms or four weeks from the first confirmed positive specimen in those who are asymptomatic. For children and young people who developed paediatric multisystem inflammatory syndrome temporally associated with COVID-19 infection (PIMS-TS) and then become eligible for vaccination, current advice suggests that an interval of three months should be observed, although earlier administration can be considered in those at risk of infection and/or who are fully recovered [1].

No safety concerns have been noted from vaccinating those with past COVID-19 infection or detectable COVID-19 antibodies [1].

Having prolonged COVID-19 symptoms is not a contraindication to receiving COVID-19 vaccine, but if the individual is seriously debilitated, still under active investigation, or there is evidence of recent deterioration, deferral of vaccination may be considered to avoid incorrect attribution of any change in the person’s underlying condition to the vaccine [1].

Adverse reactions

Local reactions at the injection site are common and other symptoms including fever, muscle and joint aches, fatigue and headache are reported with these vaccines. Following COVID-19 vaccination, a mild fever, which usually resolves within 48 hours, is a common, expected reaction and isolation is not required unless COVID-19 is suspected.

Individuals who experience severe expected reactions after a first dose of AstraZeneca or Pfizer BioNTech vaccines appear to have a higher rate of such reactions when they receive a second dose of the alternate vaccine. Individuals should complete the course with the same vaccine, except for individuals who experience anaphylaxis and or an episode of thrombosis with low levels of platelets (thrombocytopenia) [1].

A rare condition involving serious thromboembolic (blood clotting) events accompanied by low levels of platelets (thrombocytopaenia), has been reported after AstraZeneca vaccination [1,4]. Currently healthy individuals under 40 years of age are offered an alternative COVID-19 vaccination (see above). Vaccinated individuals should be advised to seek immediate medical attention if they develop new symptoms from around 4 days to 4 weeks after vaccination such as:

• new onset of severe headache, which is getting worse and does not respond to simple painkillers
• an unusual headache which seems worse when lying down or bending over, or may be accompanied by blurred vision, nausea and vomiting, difficulty with speech, weakness, drowsiness, confusion or seizures
• new onset of unexplained pinprick bruising or bleeding
• shortness of breath, chest pain, leg swelling or persistent abdominal pain [4].

There are extremely rare reports of cases of myocarditis and pericarditis after COVID-19 vaccines [1]. The reporting rate appears to be highest in young males and shortly after the second dose [1]. The events are typically mild, with individuals usually recovering within a short time with standard treatment and rest. People are still advised to come forward for their first and second vaccination when invited to do so unless a health professional advises otherwise [1,8].

A very small number of cases of Guillain-Barre syndrome (GBS) have been reported after Pfizer-BioNTech, Janssen, Moderna and AstraZeneca COVID-19 vaccines [8]. There is no evidence of a higher rate of GBS in those with a previous episode of GBS and completion of full COVID-19 vaccine schedule is favourable even if diagnosis was made after a first vaccine dose [9].

Detailed information about adverse reactions following COVID-19 vaccination is available in Immunisation against infectious disease Chapter 14a.

As with all medicines and vaccines in the UK, the MHRA monitor COVID-19 vaccines on an ongoing basis to ensure their benefits continue to outweigh any risks. Regular reviews and recommendations on the use of the vaccines are published.

As COVID-19 vaccines are labelled with a black triangle, all adverse reactions occurring in individuals of any age after vaccination should be reported to the MHRA using the Yellow Card Scheme. A summary of the reports are published on the GOV.UK website.

Travel: vaccine and proof of vaccination

Currently the World Health Organization (WHO) does not recommend proof of vaccination or immunity for international travel as a condition of entry to a country until there is more scientific knowledge and equitable distribution COVID-19 vaccine globally [10]. There is no recommendation under International Health Regulations to use the International Certificate of Vaccination or Prophylaxis for proof of COVID-19 vaccination.

Rather than a condition of entry, some countries have indicated that entry requirements will be eased for travellers if proof of COVID-19 vaccination or COVID-19 immunity can be shown. Each country should indicate what would be accepted as proof of vaccination or immunity. COVID-19 testing for international travel may still be required by each country regardless of vaccination status. The Foreign, Commonwealth & Development Office (FCDO) details the current entry requirements of each country including information about self-isolation and necessary COVID-19 testing.

See further details on demonstrating COVID-19 vaccine status and useful links for those living in England, Scotland, Wales or Northern Ireland.

Whilst abroad and irrespective of the number or type of COVID-19 vaccines received, travellers should continue to follow the latest social distancing guidance, including any local requirements and maintain good hand, respiratory, and personal hygiene always.

All travellers returning to the UK must continue to follow COVID-19 testing and self-isolation requirements. These rules differ and are dependent on which countries, rated as red, amber or green for COVID-19, were visited during the ten days before arrival in England. Travellers from amber list countries, who can demonstrate proof of UK vaccination, do not generally need to quarantine on arrival in the UK. Amber country arrivals who are fully vaccinated in the USA and many European countries can also avoid quarantine in England. However, there can be exceptions to the rules for some amber countries; check the current guidance and country lists.

Falsified COVID-19 vaccines

The World Health Organization has identified falsified COVID-19 vaccine as posing a serious risk to global public health [10]. Substandard and falsified medical product alerts, are published by the WHO.

Overview of global COVID-19 vaccination programmes

There are a number of COVID-19 vaccines in clinical trials and preclinical development according to the World Health Organization.

As of 17th of September 2021, there are 16 vaccines being offered for general use worldwide as outlined below.

List of vaccines in use worldwide

* Indicates UK approved vaccines

Worldwide, as of 17th of September 2021, 206 countries have also implemented vaccination programmes with others planning to implement as shown in the map below.

A list of countries with COVID-19 Vaccination Programmes and their strategies where known is available here: Global COVID-19 Vaccination Programmes.

The vaccines landscape will be updated every 2 weeks.

Resources

• MHRA guidance on coronavirus (COVID-19)
• Public Health England: Immunisation against infectious diseases
• GOV.UK: Coronavirus (COVID-19)
• Public Health England: Coronavirus (COVID-19): guidance
• Public Health England: COVID-19 vaccination programme
• Public Health England: COVID-19 vaccination and blood clotting
• COVID-19 in brief
• World Health Organization: Substandard and falsified medical products alerts
• European Medicines Agency (EMA)