COVID-19 vaccination and MSK

ARMA BSR BOA RAIRDA

Principles for COVID-19 Vaccination in Musculoskeletal and Rheumatology for Clinicians

(Version 7, 9 June 2021)

Amendment 9th June 2021: Document updated to include MHRA approval for use of COVID-19 Vaccine Janssen (28/5/21) and extension for use of Pfizer/BioNTech vaccine to individuals aged 12 years and older (4/6/21).

Amendment 12th May 2021: Document updated to include advice about recommended vaccine for individuals aged 39 and younger and further updates about the rare condition involving serious thromboembolic events accompanied by thrombocytopaenia, has been reported after AstraZeneca vaccination.

Amendment 30th April 2021: Document updated to include age restriction for Oxford/AstraZeneca vaccine, use of COVID-19 vaccines in pregnancy, potential rare  association between thrombosis and low platelet count in patients who have received the first dose of the Oxford/AstraZeneca COVID-19 vaccine.

Amendment 31st March 2021: Document updated to include advice to vaccinate household contacts of immunocompromised patients in JCVI priority groups 4 and 6 (section 19 added).

Amendment 10th March 2021: Document updated to explain which patients are included in priority group 6, how they are being identified and recommended ways of facilitating timely vaccination by secondary care liaising with hospital hubs (preferred) and primary care.

Amendment 27th Jan 2021: Document updated to reflect updated Green Book recommendation about timings of vaccine for people due to start immunosuppression, in whom it is safe to delay by a few weeks. Please see updated sections 6, 9, 10 and 17. We are in discussions to explore how this change can be delivered and will update the document accordingly.

All patients should be encouraged to receive one of the COVID-19 vaccines. This is regardless of their treatment regimen or underlying diagnosis. The benefits of the COVID-19 vaccination outweigh the risks and by having the vaccine, this will reduce the risk of developing severe complications due to COVID-19. Vaccinations will be offered in line with the prioritisation criteria from the Joint Committee for Vaccination and Immunisation (JCVI) (please see the prioritisation section below).

We are receiving a large volume of calls from patients to our departmental advice and patient charity advice lines about the suitability and timing of the COVID-19 vaccines. It is important that we try to provide the same advice where possible.

This is a working document and it will be updated as new information/data becomes available.

The following principles may help us to achieve this:

AVAILABLE VACCINATIONS

1.There are a number of different COVID-19 vaccines under development, and as of 11thJanuary 2021 three have been approved for use by the MHRA. Table 1 lists these vaccines. The table will be updated as needed.

2. None of the current UK approved COVID-19 vaccines are considered to be ‘live’ vaccines. The COVID-19 vaccines are considered safe for use in immunosuppressed patients. Whether any new future COVID-19 vaccine is categorised as ‘live’ or not will need to be reviewed for each vaccine as it is authorised by the MHRA by looking in the summary product characteristics (SPC) document for the product. The Oxford/AstraZeneca vaccine contains a live adenovirus vector but is non-replicating so cannot cause infection and is therefore safe for people who are immunosuppressed.

3. The Pfizer/BioNTech COVID-19 mRNA Vaccine BNT162b2 has been approved for use in individuals 16 years of age and older by the MHRA and is being rolled out. The Oxford/Astra Zeneca (ChAdOx1 nCoV-2019 vaccine) was approved by the MHRA for use on 30thDecember 2020 and roll out started on 4thJanuary 2021. The Moderna vaccine was authorised for use on 8th January 2021 and rolled out started in spring/early summer 2021. The COVID-19 Vaccine Janssen was approved by the MHRA for use on 28th May 2021 and roll out will start later this year.

Table 1

[This table has five columns – scroll right]

Vaccine name Live or not live
(MHRA classification?)
Date approved by MHRA Approved for Dose
administration
Pfizer/BioNTech COVID-19 mRNA Vaccine BNT162b2 Not live 03/12/2020 12 years and older 2 doses up to 12 weeks apart
Oxford/Astra Zeneca (ChAdOx1 nCoV-2019) vaccine Not live* 30/12/2020 18 years and older** 2 doses up to 12 weeks apart
Moderna Not live 08/01/2021 18 years and older 2 doses
COVID-19 Vaccine Janssen Not Live* 28/5/2021 18 years and older 1 dose

*This vaccine contains a live adenovirus vector but it is non-replicating so cannot cause infection and is therefore safe for people who are immunosuppressed.

**Based on current evidence (May 2021) JCVI are advising a preference for a vaccine other than Oxford/AstraZeneca to be offered to healthy people aged 39 and under, including health and social care workers, unpaid carers and household contacts of immunosuppressed individuals. This advice may change if there is a change in the epidemiology or an interruption in the supply of the alternative vaccines. 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 AstraZeneca vaccine provided they have been informed and understand the relative risks and benefits. They should be given the latest version of the COVID-19 vaccination and blood clotting leaflet (https://www.gov.uk/ government/publications/covid-19-vaccination-and-blood-clotting). Those who have already received a dose of AstraZeneca vaccine should complete with the same vaccine.

4. The environment used for the administration of the vaccine should be as safe as possible for patients and staff and should adhere to the principles of social distancing and use of appropriate levels of PPE

SAFETY

5. Cautions are the same for patients as for the general population:

  • A very small number of individuals have experienced anaphylaxis when vaccinated with the Pfizer BioNTech vaccine. Following close surveillance of the initial roll out, the MHRA has advised that individuals with a history of anaphylaxis to any vaccine, medicine or food, can receive any COVID-19 vaccine as long as they are not allergic to any component (excipient) of the vaccine. The Pfizer/BioNTech COVID-19 vaccine contains polyethylene glycol (PEG), which is from a group of known allergens commonly found in medicines and also household goods and cosmetics. Known allergy to PEG is extremely rare but would contraindicate receipt of this vaccine. Of note certolizumab pegol contains PEG so patients who have had an allergic reaction to certolizumab pegol should not receive the Pfizer/BioNTech vaccine. PEG is also an excipient in the Moderna mRNA COVID-19 vaccine; individuals who have a systemic allergic reaction to the Pfizer-BioNTech vaccine should not be given a dose of the Moderna vaccine and vice versa. The British Society for Allergy and Clinical Immunology has advised that individuals with a history of immediate onset anaphylaxis to multiple classes of drugs or unexplained anaphylaxis should not be vaccinated with the Pfizer BioNtech vaccine. The AstraZeneca vaccine can be used as an alternative (if not otherwise contraindicated).
  • The vaccines should not be administered to individuals suffering from an acute severe febrile illness.
  • Patients should continue to perform social distancing/shield after their vaccination.

 6. The Pfizer/BioNTech COVID-19 mRNA Vaccine BNT162b2 and Oxford/Astra Zeneca (ChAdOx1 nCoV-2019 vaccine) vaccines are considered safe for immunocompromised persons, as they are not live vaccines. Frequently, the immune response of immunocompromised persons to these vaccine antigens is not as good as that of immunocompetent persons. Immunocompromised persons include individuals receiving immunosuppressant therapy, including corticosteroids. Detailed information and data about the efficacy of COVID-19 vaccination in the immunosuppressed are not yet available but national studies are already underway to answer this. The Green Book Chapter 14a was updated on 21st January 2021 (see point 9 below for full information).

7. Recently, a rare condition involving serious thromboembolic events accompanied by thrombocytopaenia, has been reported after AstraZeneca and COVID-19 Vaccine Janssen vaccination. There is no evidence of any underlying risk factors in the individuals affected by this condition who have mainly been previously healthy. The condition is rare, tends to present with unusual forms of clotting and the mechanism is believed to be an idiosyncratic reaction related to an immune response to the AstraZeneca vaccine. This may be related to the recipient’s polymorphisms in genes encoding Fc receptors in the immune system and is an area of active research. Because of this likely immune mechanism, there is no reason to believe that individuals with a past history of clots or of certain thrombophilic conditions would be at increased risk of this very rare condition. Similarly, although pregnancy increases the risk of clotting conditions, there is no evidence that pregnant women, those post-partum or women on the contraceptive pill are at higher risk of the specific condition of thrombosis in combination with thrombocytopaenia after the AstraZeneca vaccine. There have been no confirmed cases reported in pregnant women to date.
The contra-indications to vaccination with the AstraZeneca COVID-19 vaccine have now been amended to include individuals who have a history of a previous episode of heparininduced thrombocytopenia and thrombosis (HITT or HIT type 2). These individuals may be offered vaccination with an alternative COVID-19 vaccine.
The condition presents with unusual venous thrombosis, including cerebral venous sinus thrombosis, portal vein thrombosis, and sometimes arterial thrombosis, with low platelet count and high D-dimer measurements. The condition has similarities to heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2) and patients usually have positive antibody to platelet factor 4. The majority of the events occurred between 5 and 16 days following vaccination. The current reported rate of this event in the UK is between 4 -10 per million, the higher incidence appears to be seen in younger individuals. Comprehensive advice regarding how to manage this condition is regularly updated in the Guidance from the Expert Haematology Panel (EHP) on Covid-19 Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT) and is available on the British Society for Haematology website. Overall, the JCVI, MHRA and the WHO remain clear that the benefits of vaccination outweigh this small risk for adults aged 30 years and over, adults who are clinically extremely vulnerable and those with underlying clinical risks.
Individuals who experience a clotting episode with concomitant thrombocytopaenia following the first dose of AstraZeneca vaccine should be properly assessed. If they are considered to have the reported condition, further vaccination should be deferred until their clotting has completely stabilised, and they should then be considered for a second dose of an alternative product. Based on the analogy of HITT, antibodies to platelet factor 4 may persist for around six months.
Individuals who have received the first dose of AstraZeneca vaccine without developing this rare condition are advised to receive the second dose of the same vaccine at the currently recommended interval of around 12 weeks. To date, there have been no confirmed cases of this condition after the second dose and the rate of other reactions is lower at the second dose than after the first dose of this vaccine. Using an alternative product for the second dose may be more likely to lead to common side effects.
Individuals over 30 years of age with past clotting episodes and those diagnosed with thrombophilia, whether or not they are on long term anti-coagulation, remain at risk of COVID-19 disease. There is no evidence that those with a prior history of thrombosis or known risk factors for thrombosis are more at risk of developing this immune-mediated condition of thrombosis in combination with thrombocytopaenia after the AstraZeneca vaccine. For most of these individuals, the risk of recurrent thrombosis due to COVID-19 infection, remains far greater than the risk of this syndrome. Therefore individuals with such a history should be vaccinated with any of the available vaccines (provided they are not otherwise contra-indicated).The same consideration applies to those who experience common clotting episodes after the first dose of AstraZeneca vaccine but without concomitant thrombocytopaenia.

VACCINATION OF THE CLINICALLY EXTREMELY VULNERABLE POPULATION

8. Clinically extremely vulnerable people are expected to receive a vaccination against COVID-19 before the general population. The local NHS will ensure that they receive the vaccine as safely as possible, as well as any care and support needed. Patients who have had both doses of the vaccine should continue to follow the shielding advice until further notice as we continue to assess the impact of vaccination among all groups. The people they live with should continue to follow the public health rules and guidance as long as they are in place, including if the CEV person has received the vaccine and also if they have received the vaccine.

INTERACTION WITH ONGOING TREATMENT 

9. Patients should not stop their immunosuppression.

10. It is known that some drugs e.g. rituximab reduce the response to some vaccines such as the seasonal flu vaccine. It is anticipated that patients receiving rituximab may potentially have a reduced response to the COVID-19 vaccines. It may not be possible to time the administration of the vaccine with the course/start of immunosuppression treatment. The benefits versus the risks need to be considered and discussed with the patient and a shared decision made. Patients are still advised to receive the COVID-19 vaccine. The Green Book Chapter 14a was updated on 21st January 2021. The following paragraph is now included in the Green Book: ‘As there is no evidence on response (to the COVID-19 vaccines) in immunosuppressed individuals, there is also no evidence upon which to base advice on the optimal timing of delivery. Specialists may advise their patients based on their knowledge and understanding of their immune status and likely immune response to vaccination, but should also consider the risk from COVID-19 and the patient’s likelihood of exposure. The small number of patients who are about to receive planned immunosuppressive therapy should be considered for vaccination prior to commencing therapy (ideally at least two weeks before), when their immune system is better able to make a response. Where possible, it would also be preferable for the 2-dose schedule to be completed prior to commencing immunosuppression. This would entail offering the second dose at the recommended minimum for that vaccine (three or four weeks from the first dose) to provide maximum benefit that may not be received if the second dose was given during the period of immunosuppression. Any decision to defer immunosuppressive therapy or to delay possible benefit from vaccination until after therapy should not be taken without due consideration of the risks from COVID19 and from their underlying condition. Although the immune correlates of protection are currently unknown, post-vaccination testing may be considered.’

11. Considerations regarding the use of Rituximab:

Please read point 9 before reading this point. As above, the Green Book Chapter 14a was updated on 21st January 2021. Although Roche, the manufacturer of the rituximab originator drug, has advised that a pulse of rituximab should be given ‘at least 4 weeks after a dose of the COVID-19 vaccine’, the update to the Green Book Chapter 14a on 21st January 2021 advises ‘ideally at least 2 weeks’, and the exact interval should be decided by clinician discretion. Depending on the urgency of treatment it  would be preferable for the 2-dose schedule to be completed prior to commencing rituximab by offering the second dose at the recommended minimum for that vaccine (three or four weeks from the first dose) instead of waiting up to 12 weeks. Local discussions will have to take place to explore possible logistical options to organise this e.g. the vaccinations could be done in existing hubs/centres or perhaps by a rheumatology department whichever works best for that geographical area.

The following should be considered:

  1. Rituximab should not be delayed in patients with acute severe organ-threatening multi-system disease who need urgent treatment to control their disease. In this scenario, treatment with rituximab and the concurrent administration of the vaccination should go ahead regardless of timings i.e. as soon as they are available.
  2. If a patient needs to start a new DMARD/biologic but has not been vaccinated, it may be appropriate to consider selecting an alternative DMARD / biologic medication to rituximab, if available and appropriate, e.g. in patients with rheumatoid arthritis.
  1. For patients receiving non-urgent/maintenance rituximab, consider deferring a rituximab course until 2 weeks after completing a course of the COVID-19 vaccine. Please see table 2.

Table 2 summarises the steps/schedule to be used in patients who are due to start a course of non-urgent/maintenance IV rituximab
[Scroll right on mobile devices]

COVID-19 Vaccine Brand

Pfizer/BioNTech

Oxford/AstraZeneca

Vaccine Dose 1

Give on day 0

Give on day 0

Vaccine Dose 2

Give on day 21

Give on day 28

Rituximab 1g IV

Give on day 35

Give on day 42

The following summarises the advice for the likely scenarios:

  • If a patient has been offered a date for vaccination, then vaccinate and delay rituximab as per schedule in table 2.
  • If vaccine is available now for the patient but patient is still B-cell depleted on rituximab, then do not delay vaccination until B-cells recover but vaccinate now. There is no evidence to suggest how long after a pulse of rituximab a patient should delay vaccination with the COVID-19 vaccine but consensus suggests this should ideally be 4-8 weeks after rituximab if it is ok to defer the COVID-19 vaccine. This decision may depend upon the prevalence of COVID-19. A shared decision should be made with the patient.
  • If vaccine is not available now for the patient, and it’s not safe to delay rituximab for four weeks e.g. because of organ threatening disease, then give rituximab without delay and vaccinate whenever vaccine is available
  • If vaccine is not available now, and it is safe to delay rituximab or to switch to an alternative treatment, then consider these options. A shared decision should be made with the patient. 

12. Corticosteroids: oral, intra-articular, intra-muscular or IV and timing of the COVID-19 vaccination

There are some general principles but in each case the benefits and risks should be discussed with the patient to arrive at a shared decision:
• It is safe to have the COVID-19 vaccine alongside steroid exposure, but the patient may not mount such a good immune response.
• Do not delay vaccination for someone who is taking, has received or is soon to receive steroids in any form.
• If additional steroids are required to control inflammatory disease, that may take priority, as a flare can also worsen the risk from COVID-19
• It may be appropriate to delay a non-essential steroid injection, as part of a shared decision, so that the response to the vaccine is more effective. For a patient who is on an elective waiting list for a steroid injection of up to 80mg methylprednisolone or 80mg triamcinolone, the administration of the COVID-19 vaccine is the priority if the vaccine has been offered to the patient and the prevalence of COVID-19 is high. In this scenario, the steroid injection should be deferred by 2 weeks after the vaccine, to enable the patient to mount the best response to the COVID-19 vaccine.

PRECAUTIONS AND CONTRAINDICATIONS

13. Pregnancy: The available data for the Pfizer-BioNTech and AstraZeneca COVID-19 vaccines do not show any safety concerns or harm to the mother or baby during pregnancy. Although clinical trials on the use of COVID-19 vaccines during pregnancy are not advanced, the available data do not indicate any harm to pregnancy. JCVI has therefore advised that women who are pregnant should be offered vaccination at the same time as non-pregnant women, based on their age and clinical risk group. There is now extensive post-marketing experience of the use of the Pfizer BioNTech and Moderna vaccines in the USA with no safety signals so far (https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/vsafepregnancyregistry.html). These vaccines are therefore the preferred vaccines to offer to pregnant women. Clinicians should discuss the risks and benefits of vaccination with the woman, who should be told about the limited evidence of safety for the vaccine in pregnancy.

14. Breastfeeding: There is no known risk associated with giving non-live vaccines whilst breastfeeding. The JCVI advises that breastfeeding women may be offered vaccination with the Pfizer-BioNTech or AstraZeneca COVID-19 vaccines, following a discussion about the developmental and health benefits of breastfeeding along with the mother’s clinical need for immunisation against COVID-19, and the woman should be informed about the absence of safety data for the vaccine in breastfeeding women.

15. Elective surgery: It is recommended that people undergoing elective surgery have 7 days between the vaccination and surgery (both before and after surgery). This applies to both doses of the vaccine. The rationale for separating the date of surgery from vaccination is so that any symptoms such as fever post vaccination might be correctly attributed to the consequences of either vaccination or the operation itself. People underdoing elective surgery who have been vaccinated are still asked to self-isolate prior to surgery and take a COVID test before surgery.

 16. Urgent/emergency surgery: For those requiring urgent/emergency surgery, surgical intervention should proceed.

PRIORITISATION

Table 3 outlines the priority groups for vaccination as advised by the JCVI:

Priority group  
1

Residents in a care home for older adults

Staff working in care homes for older adults

2

All those 80 years of age and over

Frontline Health and social care workers

3 All those 75 years of age and over
4

All those 70 years of age and over

Clinically extremely vulnerable individuals (not including pregnant women and those under 16 years of age)

5 All those 65 years of age and over
6

Adults aged 16 to 65 years in an at-risk group

7 All those 60 years of age and over
8 All those 55 years of age and over
9 All those 50 years of age and over

 

17. All clinicians should continue to identify patients who are at the highest risk from COVID-19 (the Clinically Extremely Vulnerable (CEV)), and submit their details to NHS Digital, so that they can be added to the shielded patients list (SPL). All NHS Trusts have a mechanism to do this. Decision-support tools to help identify these patients are available on the British Society for Rheumatology’s (BSR) website. This is guidance, and ultimately the decision to submit patient details to NHS Digital/add a person to the SPL list will be made on a case by case basis.

18. In this early phase of vaccine roll out, it may not be possible to deliver the vaccine to all patients with urgent clinical need e.g. patients who are due to commence a course of rituximab in the next couple of months. However, this may be something that is possible in the near future as logistics become easier, particularly in light of the Green Book Chapter 14a amendment on 21st January 2021, as fully reported in point 9 above. Clinicians may be able to recommend that a patient should receive a vaccination at a specific time to optimise response according to the treatment schedule by contacting their local vaccination hub e.g. for a small number of patients receiving non-urgent/maintenance rituximab as outlined in point 9. We will continue to have discussions about the logistics of trying to deliver this pragmatic approach with NHS England and will update this document accordingly.

19. Identification of priority group 6: Table 3 in Chapter 14a of the Green Book lists the clinical risk groups 16 years of age and over who should receive COVID-19 vaccination. It includes this list of drugs: individuals who are receiving immunosuppressive or immunomodulating biological therapy including, but not limited to, anti-TNF, alemtuzumab, ofatumumab, rituximab, patients receiving protein kinase inhibitors or PARP inhibitors, and individuals treated with steroid sparing agents such as cyclophosphamide and mycophenolate mofetil. Individuals treated with or likely to be treated with systemic steroids for more than a month at a dose equivalent to prednisolone at 20mg or more per day for adults. The examples above are not exhaustive, and, within these groups, the prescriber should apply clinical judgment to take into account the risk of COVID-19 exacerbating any underlying disease that a patient may have, as well as the risk of serious illness from COVID-19 itself. GPs are also identifying these patients by using a list of SNOMED codes, which are not exhaustive so some eligible patients may be inadvertently missed. We recommend that such patients should also be referred to a hospital hub or flagged to a GP so that they receive timely vaccination.

20. Roll out of the COVID-19 vaccine to adult household contacts (over 16 years of age) of adults with severe immunosuppression (includes individuals in priority groups 4 and 6): On 31st March 2021, the NHS wrote to GPs to ask them to identify individuals in priority groups 4 and 6, to write to these individuals and to inform them that the adult household contacts of adults with severe immunosuppression are now eligible to receive the COVID-19 vaccine (using a template letter), and then to roll out the vaccine in this cohort, alongside priority group 6 (references C1228 and C1235). The JCVI has been regularly monitoring data on vaccine effectiveness and impact from the vaccine roll out. Early data indicate lower protection in vaccinated adults who are immunosuppressed. Those with severe immunosuppression are therefore more likely to suffer poor outcomes following infection and are less likely to benefit from the vaccines offered. The JCVI notes there are now data indicating the potential for a reduction in transmission in those vaccinated. They have now advised that adult household contacts (over 16 years of age) of adults with severe immunosuppression are offered the COVID-19 vaccine alongside priority group 6. The JCVI advises this will reduce the risk of infection in the immunosuppressed who may not fully benefit from vaccination. The JCVI recommends defining adult household contacts as individuals who expect to share living accommodation on most days… and therefore for whom continuing contact is unavoidable. Household contacts will have to provide the household contact letter and formal identification when they attend for their vaccine appointment. On 31st March 2021, the NHS also wrote to medical directors to inform them of the JCVI advice and asked them to cascade this information to relevant departments and clinical teams. The specialist team can organise vaccination at the acute trust if possible, or inform the immunosuppressed individual’s GP that their household contacts are eligible for vaccination and advise the individual to contact their registered GP.

FURTHER QUESTIONS

The data and evidence regarding the safety and effectiveness of the COVID-19 vaccines continues to emerge. Many unanswered questions remain but data are being collected to try to answer these questions.

These questions include:

  • ‘How long does the vaccine last/ what is the duration of immunity?’
  • ‘Should methotrexate be suspended temporarily around the time of the COVID-19 vaccine?’

This document will be updated as new evidence emerges to answer these and other current pertinent questions.

REFERENCES

JCVI website:
https://www.gov.uk/government/groups/joint-committee-on-vaccination-and-immunisation

Green book chapter 14a COVID-19- SARS-CoV-2:
https://www.gov.uk/government/publications/covid-19-the-green-book-chapter-14a
– and –
assets.publishing.service.gov.uk/government/uploads … Information_for_Healthcare_Professionals_on_Pfizer_BioNTech.pdf

BSR website: rheumatology.org.uk/covid-19/

Versus Arthritis website: www.versusarthritis.org/news/2020/april/coronavirus-covid-19-and-arthritis-where-to-go-for-information/

Decision Support Tool: https://www.versusarthritis.org/media/23478/msk-rheumatology-decision-support-tool-april-2021.pdf 

Royal College of Obstetricians and gynaecologists: www.rcog.org.uk/en/news/covid-19-vaccination-and-pregnancy/

Acknowledgements

We are grateful to the members of the NHS England and NHS Improvement musculoskeletal stakeholder group led by National Clinical Director for Musculoskeletal, the specialised rheumatology clinical reference group, the Behaviour Change Unit and the British Society for Rheumatology COVID group, for their input and review of the different iterations of this draft document.