COVID-19 immunisation and immunomodulators/ biologic agents

The development and rollout of COVID-19 vaccines is rapidly evolving. This DermNet webpage may quickly become outdated.

COVID-19 vaccines

Many strategies are under development to produce effective safe vaccines against SARS-CoV-2, the virus causing COVID-19. Examples of vaccines approved for use or in Phase III trials currently include:

mRNA vaccines

• BNT162b2; COMIRNATY: BioNTech/Pfizer
• mRNA-1273: Moderna

Non-replicating Viral Vector vaccines

• AZD1222; ChAdOx1-S: University of Oxford/AstraZeneca
• JN-78436735; Ad26.COV2S: Johnson & Johnson/Janssen Biotech Inc

Protein Subunit vaccine

• NVX-CoV2373: Novavax

Other COVID-19 vaccine strategies under development

• Non-live vaccines — inactivated SARS-CoV-2 virus; virus-like particles which deliver SARS-CoV-2 proteins into cells; injected DNA that codes for a SARS-CoV-2 protein
• Live vaccines — live attenuated SARS-CoV-2 virus; live attenuated carrier viruses to deliver the genetic code for a SARS-CoV-2 protein.

What is known about immunising immunocompromised patients?

Ideally immunisations should be completed at least one month prior to starting immunomodulating therapies.

Immunomodulatory therapies and/or biologics should not be stopped prior to vaccination. However, decreased immune response and vaccine immunogenicity has been found with some (but not all) systemic immunosuppressive drugs and biologics.

Close contacts, such as household members, of an immunocompromised patient should also be vaccinated (‘ring-fencing’) to provide local herd immunity.

Rituximab acts on B-cells which are the antibody-producing cells. The antibody response to an immunisation is therefore impaired for at least 5 months and perhaps up to 12 months after an infusion. Non-live vaccines should be given at least one month before and at least five months following a rituximab infusion.

[see Immunisation in immunosuppressed dermatology patients]

What are the contraindications to immunising immunocompromised patients?

Live viral vaccines should not be administered to immunosuppressed patients due to the risk of developing a vaccine infection. Ideally these should be administered before starting immunomodulatory treatment.

What do the COVID-19 vaccine clinical trials tell us about immunising immunocompromised patients?

There is limited information regarding safety and efficacy in immunocompromised patients from the COVID-19 vaccine clinical trial data at this time.

Although people with stable HIV disease were included in phase III trials of some COVID-19 vaccines, the safety and efficacy data has not been reported separately. Patients with significant immunosuppression were not included in the clinical trials.

As the COVID-19 vaccine rollout extends around the world in the real population, more data will become available about efficacy and safety in various subgroups of immunocompromised vaccine recipients.

Studies have shown that methotrexate may reduce the efficacy of the response to covid immunisations. Stopping methotrexate for 2 weeks after immunisation allows for a good immune response to the vaccination, without a significant reduction in control of psoriasis/psoriatic arthritis or eczema that the methotrexate was prescribed for.

Until such data becomes available, vaccinated immunocompromised patients are advised to continue social distancing and hygiene measures to minimise their risk of SARS-CoV-2 infection.

What are the current recommendations for COVID-19 vaccination of immunocompromised patients?

COVID-19 immunisation should be completed prior to initiation of immunomodulators when possible.

COVID-19 immunisation with a non-live vaccine is strongly encouraged for immunocompromised patients, except for those with a history of anaphylaxis or severe allergy to the vaccine or its ingredients.

Immunomodulatory treatment and/or biologics should not be stopped prior to COVID-19 immunisation but, if possible, the vaccine should be administered at least 7 days on either side of treatment dosing.

Emerging data on persistence of the humoral response after standard COVID-19 vaccination supports a third dose in patients with disorders that reduce their antibody response (eg, solid organ transplant, systemic lupus erythematosus) or who are on immunomodulatory drugs (eg, high dose prednisone, B-cell depleting drugs such as rituximab). It is likely a booster dose of mRNA COVID-19 vaccine will also be recommended for all individuals who are at risk of severe COVID-19 disease.

Due to the lack of safety data, co-administration of COVID-19 vaccine and other immunisations should be separated by at least 1 week and different anatomic locations should be used for each.

Consider checking antibody titres after immunisation as the anticipated efficacy is variable.

What are the adverse reactions to COVID-19 vaccines?

All COVID-19 vaccine recipients should be educated on potential adverse reactions.

Cutaneous reactions are common, including injection site erythema and swelling in 5–10% of mRNA vaccine trial recipients. These are usually mild and self-limiting.

Vaccination site pain, fatigue, headache, myalgia, chills, arthralgia, and fever are reported in at least 10% of recipients.

Delayed large local reactions have been reported following the first injection of mRNA COVID-19 vaccines, developing on average 8 days (range, 4-11 days) later and resolving after 6 days (range, 2-11 days). This is thought to be a delayed-type T-cell-mediated hypersensitivity. This is not a contraindication to having the second injection as in half the cases there was no reaction after the second dose, and one quarter had a milder reaction. One-quarter of patients had a similar reaction the second time, but none were worse. Reactions after the second dose occurred after 2 days (range, 1-3 days).

Anaphylaxis or severe hypersensitivity reaction to COVID-19 vaccinations have been reported in 2.5–11.1 cases per million doses, largely in individuals with a history of allergy; the second vaccine dose is currently contraindicated if documented anaphylaxis follows the first dose, although this advice may change. At-risk patients such as those with severe asthma or mastocytosis who have had a previous recurrent anaphylaxis are advised to have the vaccine administered in a hospital setting.

In a recent study of 65,000 recipients of the first dose of a mRNA COVID-19 vaccine, anaphylaxis was confirmed in 16 (0.025% [95%CI 0.014%–0.040%]). This equates to a rate of 2.47 per 10,000 vaccinations. The mean age was 41 years (SD, 13 years), 15/16 (94%) were female, 10/16 (63%) had a prior allergy history, and 5/16 (31%) had a history of prior anaphylaxis. The mean time to anaphylaxis onset was 17 minutes (SD, 28 minutes; range 1–120 minutes). All individuals recovered without requiring intubation.

For more information see Skin reactions to COVID-19 vaccines.

Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.

We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).