COVID-19 vaccination and MSK


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

(Version 12, 12 September 2022)

Amendment 12th September 2022: Document updated to include latest JCVI and NHSE guidance regarding autumn boosters using second generation bivalent COVID-19 vaccines and results of VROOM study (see section 23 and section 24 respectively)

Amendment 3rd April 2022: Document updated to include latest JCVI and NHSE guidance regarding spring 2022 boosters (see section 22)

Amendment 3rd December 2021: Document updated to include latest JCVI guidance regarding boosters for patients who were eligible for a third primary dose (see end of section 21)

Amendment 13 October 2021: Document updated to include revised BSR wording about third primary dose (section 20).

Amendment 20 September 2021: Document updated to include JCVI advice about third primary dose in immunosuppressed individuals (section 20), booster doses for vaccine groups 4 and 6 (section 21), small number of cases with myocarditis and pericarditis in particularly in males under 25 years of age after the second dose of Pfizer BioNTech and Moderna COVID-19 vaccines (section 8), update on prior PEG allergy and mRNA vaccines (section 5).

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:


  1. There are a number of different COVID-19 vaccines under development, and a number 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 can not 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 5 years of age and older by the MHRA (dose varies according to age). The Oxford/Astra Zeneca (ChAdOx1 nCoV-2019 vaccine) was approved by the MHRA for use on 30th December 2020 and roll out started on 4th January 2021. The Moderna vaccine was authorised for use on 8th January 2021 and roll out started in spring/early summer 2021. The COVID-19 Vaccine Janssen was approved by the MHRA for use on 28th May 2021. The MHRA has approved the use of the Moderna and Pfizer bivalent vaccines (summer 2022) and these will be used in the roll out during autumn 2022.

Table 1

[This table has five columns – scroll right]

Vaccine name Live or not live
(MHRA classification?)
Date approved by MHRA Approved for Primary course dose
Pfizer/BioNTech COVID-19 mRNA Vaccine BNT162b2 Not live 03/12/2020 5 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 12 years and older 2 doses
COVID-19 Vaccine Janssen Not live* 28/5/2021 18 years and older 1 dose
Nuvaxovid developed by Novavax Not live   18 years and older 2 doses with a minimum of 3 weeks apart

Second generation vaccine:

Moderna bivalent (Spikevax® bivalent Original/Omicron vaccine)

Not Live August 2022    

Second generation vaccine:

Pfizer BioNTech (Original/Omicron BA.1 Comirnaty®)

Not Live September 2022    

*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 ( 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


  1. 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 some household goods and cosmetics. Known allergy to PEG is extremely rare but would be a relative contraindication; however some individuals with prior allergic reaction to PEG-containing medicines can tolerate the PfizerBioNTech vaccine. Expert advice should be obtained and if a decision is made to administer an mRNA vaccine, then this should be done in hospital under medical supervision. 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 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 after their vaccination.
  1. The Pfizer/BioNTech COVID-19 mRNA Vaccine BNT162b2, Moderna 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 now emerging from national studies (e.g. OCTAVE study – preliminary data published August 2021).
  2. 7. Thrombosis and thrombocytopenia syndrome (TTS) occurring after COVID-19 vaccination: This is a rare condition involving serious thromboembolic events accompanied by thrombocytopaenia. It 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 idiosyncraticreaction 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 heparin induced 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 around 15 cases per million, although a higher incidence is 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.

  3. A number of cases of myocarditis and pericarditis have been reported after the Pfizer BioNTech and Moderna vaccines. The reported rate appears to be highest in those under 25 years of age and in males, and after the second dose. Onset is usually within a few days of vaccination. Most cases are mild and patients have recovered without any sequelae. The MHRA has advised the benefits of vaccination still outweigh any risk in most individuals. A booster dose of Pfizer BioNTech vaccine should be considered once the patient has fully recovered. Emerging evidence suggests that an interval of at least 12 weeks should be observed from the previous dose. Pfizer BioNTech is preferred over Moderna due to a slightly higher rate of myocarditis reported after the latter vaccine; AstraZeneca should not be offered to those who have previously received an mRNA vaccine given the more serious nature of thrombosis and thrombocytopenia syndrome. A very small number of cases of Guillain-Barre Syndrome (GBS) have been reported after Pfizer-BioNTech vaccination but these reports have not reached the number expected to occur by chance in the immunised population.


  1. People previously defined as clinically extremely vulnerable (CEV) were offered vaccination against COVID-19 before the general population (see table 3 = vaccine priority group 4). Patients who have had both doses of the vaccine should continue to follow the public health guidance. The people they live with should continue to follow the public health 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.


10. Patients should not stop their immunosuppression but may wish to pause it around the time of the vaccine if their disease is under good control (see section 24)..

11. It is known that some drugs e.g. rituximab reduce the response to some vaccines such as the seasonal flu vaccine. 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. There is no evidence to guide 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 vaccination 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 COVID-19 vaccine 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.’

12. Considerations regarding the use of rituximab:

Please read point 11 before reading this point. 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 vaccination 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.
  3. 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



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.
  1. 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.


  1. 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. 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 ( 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.
  2. 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.
  3. 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.

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


Table 3 outlines the priority groups for vaccination as advised by the JCVI for phase 1 with the aim of reducing COVID-19 specific mortality::

Priority group  

Residents in a care home for older adults

Staff working in care homes for older adults


All those 80 years of age and over

Frontline health and social care workers

 3 All those 75 years of age and over

All those 70 years of age and over

Individuals aged 16 to 69 in a high risk group (previously known as clinically extremely vulnerable individuals)

 5 All those 65 years of age and over

Adults aged 16 to 65 years in an at-risk group (includes those on immunosuppression – see section 18)

 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

Since the shielding programme has ended, groups 4 and 6 have been formally merged.

18. 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.

19. Roll out of the COVID-19 vaccine to household contacts (over 12 years of age) of adults with severe immunosuppression (includes individuals in priority groups 4 and 6).On 31stMarch 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 (16 and above) household contacts of adults with severe immunosuppression were 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. In August 2021 this advice was extended to all individuals aged over 12 years who are contacts of immunosuppressed individuals i.e. those aged 12 years and above who expect to share living accommodation on most days (and therefore for whom continuing close contact is unavoidable) with individuals of any age who are immunosuppressed.

  1. Third primary dose for those aged 12 years or over who are immunosuppressed


Some individuals who are immunosuppressed due to underlying health conditions or medical treatment may not mount a full immune response to COVID-19 vaccination. Preliminary results from UK studies of real-world vaccine effectiveness (VE) in persons who are immunosuppressed suggest only a modest reduction in VE against symptomatic COVID-19, but confidence intervals are wide and overlap with VE estimates for persons who are not immunosuppressed.

A few published studies describing the effect of a third dose of mRNA vaccine in persons who are immunosuppressed report increased immune responses in varying proportions of persons. The OCTAVE-DUO trial is a phase 3 multicentre trial randomising patients in the UK to a third dose of Pfizer-BNT162b2 or Moderna mRNA-1273 with immunogenicity outcomes. The trial is expected to report early results in mid to late September and will probably not have sufficient granularity to inform the management of all types of immunosuppression. mRNA vaccines are being used based on consistent evidence of higher antibody levels, even though some studies suggest that cellular responses with AstraZeneca Vaxzevria vaccine are as good or better than after mRNA vaccines. Emerging evidence suggests that both antibody and cellular immune responses to the primary course are enhanced with heterologous schedules, and therefore a third primary dose with a different vaccine format may be beneficial.

Based on experience with other vaccines, it is expected that some persons who are immunosuppressed may not generate a good immune response regardless of the number of vaccine doses administrated. However, data are not currently available to reliably identify who might, or might not, benefit from a third primary dose of a COVID-19 vaccine. A few studies have suggested that timing of vaccine administration in relation to the underlying disease process or therapy is important in determining the level of immune response.

The JCVI recognises that many persons who are immunosuppressed remain concerned regarding their risk of COVID-19 despite having received 2 doses of the primary vaccine schedule as currently advised. The potential for additional protection from a third primary dose is unknown at an individual level. While antibody levels may be measured, without a clear understanding of the correlates of protection against severe disease and the interaction of immune suppression with measured immune responses, clinical inferences based on the measurement of antibody levels in persons who are immunosuppressed are difficult. For instance, low antibody levels may not denote poor protection against severe disease; and conversely, high antibody levels in a person unable to generate a commensurate cellular response may not denote good protection against severe disease.

At the current time (1st September 2021), the JCVI advises that a third primary dose be offered to individuals aged 12 years and over with severe immunosuppression in proximity of their first or second COVID-19 vaccine doses in the primary schedule.

JCVI advice relevant to rheumatology patients: severe immunosuppression at the time of vaccination is defined using the guidance and timings stated below:

Individuals on immunosuppressive or immunomodulating therapy at the time of first and/or second vaccination including:

  • Rituximab in previous 6 months
  • JAK inhibitors or biologic immune modulators including B-cell targeted therapies (but see above for rituximab – a 6-month period applies), T-cell co-stimulation modulators, monoclonal tumour necrosis factor inhibitors (TNFi), soluble TNF receptors, interleukin (IL)-6 receptor inhibitors, IL-17 inhibitors, IL 12/23 inhibitors, IL 23 inhibitors in the previous 3 months (note: this list is not exhaustive)
  • cDMARDs such as methotrexate >20mg per week (oral and subcutaneous), azathioprine >3.0mg/kg/day, 6-mercaptopurine > 1.5mg/kg/day, mycophenolate > 1g/day in previous 3 months
  • high-dose steroids (equivalent to > 40mg prednisolone per day for more than a week) for any reason in the month before vaccination.
  • high-dose corticosteroids (equivalent to = 20mg prednisolone per day) for more than 10 days in the previous month
  • long-term moderate dose corticosteroids (equivalent to = 10mg prednisolone per day for more than 4 weeks) in the previous 3 months
  • certain combination therapies at individual doses lower than above, including those on = 7.5mg prednisolone per day in combination with other immunosuppressants (other than hydroxychloroquine or sulfasalazine) and those receiving methotrexate (any dose) with leflunomide in the previous 3 months

Other relevant scenarios:

  • those with lymphopaenia (<1,000 lymphocytes/ul) or with a functional lymphocyte disorder
  • persistent agammaglobulinaemia (IgG < 3g/L) due to primary immunodeficiency (for example, common variable immunodeficiency) or secondary to disease/therapy
  • those who were receiving or had received immunosuppressive therapy for a solid organ transplant in the previous 6 months
  • those who were receiving or had received in the previous 6 months immunosuppressive chemotherapy or radiotherapy for any indication

The BSR recommends a pragmatic approach in identifying these patients for a third dose as part of the primary vaccination schedule COVID-19 guidance | British Society for Rheumatology and states ‘nearly all rheumatology patients (aside from those solely on hydroxychloroquine or sulfasalazine) should receive a third primary dose’.

The guidance is specific with respect to certain drugs and the timings of when the patient has had their previous injections (see NHSE & I letter). Every effort should be made to ascertain what medication the patient is on and what medication they were on at the time of their first and second vaccines in order to explicitly follow the JCVI guidance. While some departments can easily identify these patients, for others it may be more difficult, especially acknowledging variation in steroid dosing over time, steroid use during flares, and also split prescribing roles between primary and secondary care for DMARDs. Most patients on DMARDs (except HCQ and SSZ), biologics, JAK inhibitors, and some of those on prednisolone > 10mg should have a third vaccine dose to enhance primary vaccination effectiveness. There are important caveats regarding doses, so please read the JCVI guidance in full.’

The Royal College of Physicians has also published a document on COVID-19 vaccination for people who are severely immunosuppressed: third primary dose COVID-19 vaccination for people who are severely immunosuppressed | Third primary dose | RCP London

Choice of vaccine:

For those aged 18 years and over, the JCVI advises a preference for mRNA vaccines for the third primary dose, with the option of the AstraZeneca Vaxzevria vaccine for individuals who have received this vaccine previously where this would facilitate delivery. In exceptional circumstances, persons who received a mRNA COVID-19 vaccine previously may be offered a third primary dose of AstraZeneca Vaxzevria vaccine following a decision by a health professional on a case-by-case, individualised basis.

For those aged 12 to 17 years the Pfizer-BNT162b2 vaccine remains the preferred choice, as set out in JCVI advice of 4 August 2021.

Identifying patients and timing:

The specialist involved should advise on whether the patient fulfils the eligibility criteria and on the timing of any third primary dose.

In general, vaccines administered during periods of minimum immunosuppression (where possible) are more likely to generate better immune responses.

The third primary dose should ideally be given at least 8 weeks after the second vaccine, with special attention paid to current or planned immunosuppressive therapies.

As with current advice in the Green book (chapter 14a) JCVI has advised that:

Most individuals whose immunosuppression commenced at least 2 weeks after the second dose of vaccination do not require a third primary dose at this stage. However, they are eligible for a booster dose as part of a routine booster programme.

It is expected that severely immunosuppressed individuals will become eligible for a booster dose as part of a routine booster programme from around 6 months after their third primary dose, pending further advice.


To optimise vaccine use, specialists should take responsibility for providing clear advice to the patient’s general practitioner about the need for a third primary dose of vaccine and the optimal timing. NHSE has produced a template letter (reference C1399). Patients can be identified from speciality databases and registries, pharmacy high-cost drugs databases, primary care records and the shielding list.

Organisational support within deployment teams to enable vaccination of these persons within the optimal timing window for them should be considered a priority. Presumably, more information on the pragmatic ways to roll out the third dose will become available in the near future.

Booster vaccine (4th dose) for patients eligible for a third primary dose i.e. the severely immunosuppressed: The JCVI announced on 29th November 2021 that patients who have received a third primary dose of the COVID-19 vaccine should be offered a booster dose with a minimum of 3 months between the third primary and booster dose, in response to the Omicron variant. Those who have not yet received their third dose may be given the third dose now to avoid further delay.

  1. Booster vaccine after primary course (autumn 2021) The JCVI recommended on 14th September 2021 that patients in priority vaccine groups 1-9 and household contacts of immunosuppressed individuals should be offered a booster vaccine 6 months after their second dose/primary course. The JCVI advises a preference for the Pfizer-BioNTech vaccine regardless of which vaccine brand someone received for their primary dose. If the Moderna vaccine is offered, then only half a dose (50 microg) should be given (to reduce rates of local and systemic symptoms but still achieve good immunogenicity). Where mRNA vaccines are not suitable, vaccination with AstraZeneca vaccine may be considered. This advice is separate from and dose not supersede the JCVI advice on a third primary dose for the severely immunosuppressed.

    On 29th November 2021 the JCVI announced that booster vaccination eligibility should be expanded to include all adults aged 18 years and over. Priority will still be given to older adults and those in COVID-19 at-risk groups. The booster vaccine should not be given within 3 months of completion of the primary course.

On 29th November 2021 the JCVI announced that booster vaccination eligibility should be expanded to include all adults aged 18 years and over. Priority will still be given to older adults and those in COVID-19 at-risk groups. The booster vaccine should not be given within 3 months of completion of the primary course.

22. Spring 2022 booster vaccine: In February 2022, the JCVI recommended that patients who are immunosuppressed (includes patient who were in vaccine priority groups 4 and 6 – see table 3 above) and aged 12 years and over should receive a spring booster vaccine (Pfizer or Moderna). This should be given 91 or more days after their last COVID-19 vaccine. If the individual has recently contracted COVID-19, then the booster should be given 28 days or more after the onset of the infection. Individuals who had a booster (4th dose) after their third primary dose administered will be eligible for a spring booster (5th dose) 91 or more days after their 4th

If an individual has missed an earlier dose of the COVID-19, then the vaccine can be given and the subsequent schedule followed. If an individual did not receive their first booster by March 2022, they may be given the spring booster provided there is at least 91 days from the previous dose. An additional dose is not then recommended before the autumn.

Eligible individuals are being invited for their spring booster vaccine. Individuals who had their last vaccine more than 6 months ago are being prioritised.

23. The autumn booster campaign 2022 Following on from the spring campaign, the JCVI has recommended a move to regular, planned and targeted boosting as the most important strategy to control COVID-19. For the 2022 autumn booster programme, the primary objective is to augment immunity in those at higher risk from COVID-19 and thereby optimise protection against severe COVID-19, specifically hospitalisation and death, over winter 2022/23.

The following groups should be offered a COVID-19 booster vaccine in the autumn of 2022:
● residents in a care home for older adults and staff working in care homes for older adults
● frontline health and social care workers
● all adults aged 50 years and over
● persons aged 5 to 49 years in clinical risk groups 4 and 6, as set out in Table 3
● persons aged 5 to 49 years who are household contacts of people with immunosuppression (as defined above)
● persons aged 16 to 49 years who are carers of people with immunosuppression (as defined above).

The booster will be available for booking via the National Booking System from 5 September 2022 and will be delivered from 12 September 2022. People over 75, health and social care workers will be given priority and then the invitation will be extended to other groups. Immunosuppressed individuals can self-declare and attend walk-ins for their vaccination in line with existing guidance. The aim should be to complete the campaign before December 2022. The vaccine should be administered at least 3 months from a previous dose. A bivalent vaccine will usually be offered but there are slightly different recommendations for different ages below 18 years – please see Green book chapter 14a. The Novavax vaccine will be available for those who cannot receive the mRNA vaccine.

24. Results of the Vaccine response on/off methotrexate (the VROOM) study (Lancet Respir Med 2022; 10: 840–50): A 2-week interruption of methotrexate treatment (any dose, oral or subcutaneous) for people with immune-mediated inflammatory diseases (IMID) after a COVID-19 booster vaccine resulted in enhanced boosting of antibody responses after COVID-19 vaccination (2.19 fold increase) in this randomised open label superiority trial (n = 254). Significantly more patients in the withhold methotrexate group reported an increase in self-reported disease activity at 4 weeks compared with the continuation group. The flare had generally settled by 12 weeks and was usually self-managed. These data help physicians and patients to make an informed decision on the risks versus the benefits of whether to continue or temporarily suspend methotrexate at the time of a COVID-19 booster vaccine.

The following links may be useful:

To book COVID-19 vaccination appointments visit or call 119

For information on local walk-in sites visit

It will be helpful for the individual when attending their vaccination appointment or visiting a walk-in site, to present relevant medical documentation confirming their condition/medication such as a clinic letter and/or prescription.


JCVI website:

Green book chapter 14a COVID-19- SARS-CoV-2:
– and – … Information_for_Healthcare_Professionals_on_Pfizer_BioNTech.pdf

BSR website:

RCP website: COVID-19 vaccination for people who are severely immunosuppressed | Third primary dose | RCP London

Versus Arthritis website:

Decision Support Tool:

Royal College of Obstetricians and gynaecologists:


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.