Information about rare side effects associated with COVID-19 vaccination focusing on blood clotting, myocarditis and Guillain-Barre syndrome.

Blood clotting

The UK Health Security Agency (UKHSA) information for healthcare professionals on blood clotting following COVID-19 vaccination outlines what is currently known and provides advice on action to take.

Incidence and vaccines implicated

Thromboembolic events (blood clots) accompanied by thrombocytopenia (low platelets) following administration of the first dose of AstraZeneca COVID-19 vaccine have been reported. There is currently no evidence of association with the Pfizer-BioNTech or Moderna vaccines. Based on reports to 11 August 2021, the overall incidence following the AstraZeneca vaccine is 14.9 per million first or unknown doses and 1.8 per million second doses administered. For the latest information please see the weekly summary from the MHRA.

In response to reporting of thromboembolic events the Joint Committee on Vaccination and Immunisation (JCVI) updated their advice on which vaccines to use in specific age groups. This followed the observation of a trend towards an increased incidence of thromboembolic events in younger people.

Age group specific advice

The benefit and risk analysis from the MHRA and JCVI is outlined in a UKHSA leaflet about COVID-19 vaccination and blood clotting.

Aged 40 years and over or with underlying medical condition

People should still receive any of the available COVID-19 vaccines and should also complete the course with the same vaccine they had for the first dose (except where there are specific contraindications).

Aged 30 to 39 and healthy

JCVI advise alternative vaccines to the AstraZeneca vaccine should be offered to people in this age group where possible.

Vaccination with any vaccine is always better than no vaccination, except where there are specific contraindications. Where AstraZeneca is the only practical option, the benefits of receiving this vaccine outweigh the risks and people in this age group should be offered it.

Aged 18 to 29 and healthy

JCVI advise it is preferable for people under 30 to have a vaccine other than AstraZeneca.

Second dose

No serious side effects to first dose

Complete the course with AstraZeneca COVID-19 vaccine. This includes people aged 18 to 39 years who are health and social care workers, unpaid carers and family members of those who are immunosuppressed.

Serious side effects to first dose

AstraZeneca manufacturer’s information contraindicates use of  AstraZeneca COVID-19 vaccine in those who have experienced major venous and/or arterial thrombosis occurring with thrombocytopenia syndrome following vaccination. Complete the course with an alternative vaccine.

Diagnosing and managing COVID-19 vaccine associated clotting disorders

A detailed review is ongoing jointly by the MHRA, UKHSA and the Expert Haematology Panel. The UKHSA page ‘COVID-19 vaccination and rare side effects‘ collates links to relevant national guidance.

The Royal College of General Practitioners has produced primary care guidance for management of suspected thromboembolism with thrombocytopenia after COVID-19 vaccination.

British Society for Haematology (BSH) Guidance on vaccine induced thrombosis and thrombocytopenia (VITT) outlines factors associated with unlikely, possible, probable and definite cases together with recommendations for management. Details of how to report cases are also provided.

People who have previously had VITT may present with recurrent symptoms and need to be monitored closely. The BSH have produced a haematology triage policy for patients with previous VITT.

Myocarditis and pericarditis

The UKHSA information for healthcare professionals on myocarditis and pericarditis following COVID-19 vaccination provides detailed information about what is currently known.

Vaccines implicated

UK and international data suggest an increase in cases of myocarditis and pericarditis following vaccination with both Pfizer-BioNTech and Moderna vaccines. In the UK, overall case rates per million doses for all ages after both the first and second doses are:

Pfizer-BioNTech – myocarditis 11; pericarditis 8

AstraZeneca – myocarditis 1.7; pericarditis 3.0

Moderna – myocarditis 39; pericarditis 22.

Risk factors

The UKHSA Green book suggests the reported rate of myocarditis appears highest in those under 25 years of age and in males, and after the second dose.

Pfizer BioNTech vaccine is the preferred vaccine for children and young people due to a lower reported rate of myocarditis.

Symptoms and investigations

The UKHSA has produced guidance for healthcare professionals on symptoms, investigations and follow up.

Myocarditis and pericarditis present with new onset of chest pain, dizziness, shortness of breath or feelings of having a fast-beating, fluttering, or pounding heart.

Anyone who develops these symptoms within 10 days of a COVID-19 vaccination should urgently seek medical assistance.

Second dose of vaccine in affected individuals

The UKHSA Green book Chapter 14a advises that if an individual develops myocarditis or pericarditis following the first dose of COVID-19 vaccination they should be assessed to determine whether it is likely to be vaccine related. Defer an individual’s second dose until further investigation and consideration of risks and benefits is undertaken.

For those that experience myocarditis or pericarditis within two weeks of the first dose of an mRNA vaccine, testing for N antibody may indicate prior exposure to COVID-19. These individuals are likely to be well protected and benefit from a second or subsequent dose is likely to be more limited.

Where N antibody is negative or where a further dose is considered necessary, e.g. those at higher risk of the complications of COVID-19 infection, the Pfizer-BioNTech vaccine should be given after full recovery and at least 12 weeks after the first vaccine dose.

Prior history of myocarditis or pericarditis and vaccination

A history of myocarditis or pericarditis unrelated to COVID-19 vaccination is not a contraindication to receiving a COVID-19 vaccine. Currently, there is no evidence that such people are at increased risk of a recurrence following COVID-19 vaccination. The risks and benefits of vaccination should be discussed with the individual so they can make an informed decision.

Guillain-Barre syndrome (GBS)

The UKHSA information for healthcare professionals on GBS following COVID-19 vaccination outlines what is known to date.

Following case reports of GBS, investigations are ongoing to establish if the rate of reported cases is above what would be expected in the population. GBS has a background rate of about 2 per 100,000 per year.

Pfizer-BioNTech and Moderna

A causal link has not been proven for Pfizer-BioNTech and Moderna vaccines with cases no greater than the background rate of GBS.

AstraZeneca

GBS has very rarely been reported within 6 weeks of the first dose, with the risk approximately 5.6 extra cases of GBS per million doses. Rates after the second dose are within background levels.

In Europe, the European Medicine Agency recommended the addition of a warning to raise awareness of GBS following vaccination with the AstraZeneca vaccine.

The World Health Organization suggest the potential benefits of the AstraZeneca vaccine continue to outweigh any potential risk of GBS. They conclude that a causal link between COVID-19 vaccination and GBS has not been proven and cases that occur following vaccination may occur by chance, with a background rate of GBS of 0.8-1.92 per 100,000 per year.

Prior history of GBS and COVID-19 vaccination

There is no evidence of a higher rate of reporting of GBS following COVID-19 vaccination in individuals who have previously had GBS. Hence, the balance of risk benefit is in favour of having a full COVID-19 vaccination schedule in line with their age and underlying risk status.

Second and subsequent doses of vaccine in affected individuals

There is no evidence that a previous episode of GBS predisposes an individual to further episodes. Hence, the balance of risk benefit is in favour of having a full COVID-19 vaccination schedule in line with their age and underlying risk status.

On a precautionary basis, Pfizer-BioNTech vaccine is preferred for second and subsequent doses in those who experienced GBS within 6 weeks of an AstraZeneca vaccine. Where GBS occurs following vaccination with the Pfizer-BioNTech or Moderna vaccines, further vaccination can proceed as normal, once recovered.

If the next dose is a booster dose, then the Pfizer/BioNTech vaccine is recommended.

Other rare side effects

Refer to the manufacturer’s data for Pfizer-BioNTech, AstraZeneca and Moderna vaccines or refer to the MHRA Coronavirus vaccine – weekly summary of Yellow Card reporting.

Reporting side effects

Reporting suspected COVID-19 vaccine side effects, and potential product defects or counterfeit products

Advice on reporting suspected side effects to COVID-19 vaccines. Also correct mechanisms for reporting suspected defective products and counterfeit products.

Change history

  1. Updated advice in Green book about serological testing in those who have pericarditis or myocarditis after a first vaccine dose and choice of vaccine in young people.
  1. Reviewed. Updated case rates for myocarditis and pericarditis.
  1. Updated to reflect changes in advice related to Guillain-Barre
  1. Added link to UKHSA guidance on myocarditis and pericarditis
  2. Interval between symptoms of myocarditis or pericarditis and COVID-19 vaccination changed from 2 weeks to to 10 days in line with latest UKHSA guidance
  1. Published