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 guidance on the UK groups that must be prioritised for COVID-19 vaccine can be found here: Priority groups for coronavirus (COVID-19) vaccination: advice from the Joint Committee on Vaccination and Immunisation (JCVI). The NHS will contact individuals to let them know when it is their turn to have the vaccine. Further information on the UK vaccine programme 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 in priority groups. NaTHNaC is closely monitoring recommendations and will provide travel related updates as relevant.

COVID-19 vaccines

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.

COVID-19 Vaccine Moderna

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.

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

Note these vaccines are supplied in multidose vials

The second dose of vaccine should preferably be administered using the same vaccine used for the first dose. If the same vaccine is not available, it is considered reasonable to give the vaccine available particularly if at immediate high risk of COVID-19 infection or considered unlikely to attend for vaccination again [1].

It is recommended that the second dose of both vaccines should be routinely scheduled between four and 12 weeks after the first dose. This will allow more people to benefit from the protection provided from the first dose during the roll out phase. Longer-term protection will then be provided by the second dose [1].

Based on current information about these COVID-19 vaccines, there should ideally be an interval of at least seven days with other vaccines to avoid incorrect attribution of potential adverse events [1]. 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 considered. 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. In such circumstances, patients should be informed about the likely timing of potential adverse events relating to each 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.

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

Following close national surveillance, the MHRA no longer advises that individuals with a history of anaphylaxis to food, an identified drug or vaccine do not get the vaccine, as long as they are not known to be allergic to any component (excipient) of the vaccine [1]. Polyethylene glycol (PEG) is present in the Pfizer-BioNTech and Moderna vaccines [1]. Known allergy to PEG (present in some medicines, household goods and cosmetics) is rare but if known, the individual should not receive the Pfizer-BioNTech or Moderna vaccines. 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 2^nd 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 COVID-19 vaccine AstraZeneca. The following are considered contraindications for receiving the AstraZeneca COVID vaccine:

• 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 rare immune-mediated syndromes characterised by a thrombosis with low platelet levels (thrombocytopenia), this includes those who have previously had heparin induced thrombocytopenia or the same specific clinical picture in association with anti-phospholipid syndrome [2]. These individuals may be offered an alternative COVID-19 vaccine [2].

A history of thrombosis without low platelet levels is not a contraindication to AstraZeneca COVID vaccine [2].

COVID-19 vaccine guidance is subject to regular revisions, check up to date information on COVID-19 and blood clotting on GOV.UK.

Precautions:

If acutely unwell, postpone until fully recovered.

Vaccination of those who maybe infected, asymptomatic or incubating COVID-19 infection should be delayed until clinical recovery and at least 4 weeks after symptoms onset or 4 weeks after a first PCR positive specimen in those who do not have symptoms.

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

Having prolonged COVID-19 symptoms is not a contraindication to receiving COVID-19 vaccine, but if there is evidence of current deterioration, deferral of vaccination may be considered.

The Joint Committee on Vaccination and Immunisation (JCVI) currently advises that it is preferable for adults under 30 years of age without underlying health conditions that put them at higher risk of severe COVID-19 disease, to be offered the Pfizer-BioNTech or Moderna vaccine. People may make an informed choice to receive the AstraZeneca COVID-19 vaccine to receive earlier protection [2, 3]. See statement from the JCVI and guidance for healthcare professionals for further detail.

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

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.

As with all medicines and vaccines in the UK, the MHRA monitor COVID vaccines on an ongoing basis to ensure their benefits continue to outweigh any risks. The MHRA has undertaken a thorough review into UK reports of a very rare and unlikely to occur specific type of blood clot in the brain, known as cerebral venous sinus thrombosis (CVST) occurring together with low levels of platelets (thrombocytopenia) following vaccination with the COVID-19 vaccine AstraZeneca. It is also considering other blood clotting cases (thromboembolic events) alongside low platelet levels. The MHRA publish regular reviews and recommendations on the use of the vaccines.

As the 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.

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 31st March 2021, there are currently 11 vaccines approved for general use worldwide as outlined below.

List of vaccines in use worldwide

* Indicates UK approved vaccines

Worldwide, as of 31st of March 2021, 166 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.

Falsified COVID-19 vaccines

The World Health Organization has identified falsified COVID-19 vaccine as posing a serious risk to global public health [4]. Substandard and falsified medical product alerts, are published by the WHO.

Resources

• MHRA guidance on coronavirus (COVID-19)
• 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)