SARS-CoV-2 vaccination and metabolic radionuclide therapy: Document of the SEMNIM Endocrinology Working Group

To the Editor:

At the end of 2019 the COVID-19 pandemic began, and we have remained in its grip since then.

Following the advice of different professional societies and health care authorities Nuclear Medicine Departments throughout the work adapted to the new circumstance, restructuring the planning of not only diagnostic techniques but also therapeutic procedures with radiopharmaceuticals¹. During the first months of the pandemic health care activity related to conventional nuclear medicine drastically reduced, with this reduction being much more moderate in metabolic therapy procedures and relatively low in positron emission tomography/computerized tomography studies². Later on, little by little we adapted to the new normality, and the usual numbers of diagnostic and therapeutic studies were reestablished.

Nonetheless, the arrival of the vaccines against COVID-19 has led to a new paradigm. According to data obtained from the Ministry of Health at the time of writing this article, in Spain 39.9 million doses had been administered, with more than 24 million persons having received one dose (52.8%) and more than 16 million having completed the full vaccination schedule (35.4% of the population).

In our metabolic therapy consultations we increasingly come across doubts of the patients regarding possible interactions between the vaccine and the treatment administered. On behalf of the SEMNIM Endocrinology Working Group we wish to give some recommendations on how metabolic therapy departments should act.

In Spain 4 types of vaccine against SARS-CoV-2 are currently approved:

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  Biontech/Pfizer(Comirnaty): mRNA which codifies the enveloped Spike (S) protein in lipid nanoparticles.

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  Moderna: mRNA which codifies the enveloped Spike (S) protein in lipid particles.

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  Astra-Zeneca/Oxford (Vaxzevria): replication deficient recombinant chimpanzee adenovirus expressing the Spike (S) protein.

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  Janssen: replication deficient recombinant human adenovirus expressing the Spike (S) protein.

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  According to the Summary of Product Characteristics of the four vaccines (3-available at https://cima.aemps.es/cima/publico/home.html), there are no studies of interactions with other medications and other concomitant vaccines. In the search for information on interactions currently reported with the administration of the vaccines (4-https://www.drugs.com), 264 pharmacological interactions have been described (263 moderate and one mild), being the same for each type of vaccine. These interactions include the use of [¹⁷⁷Lu]Lu-DOTA-TATE and [¹³¹I]MIBG, with treatment with [¹³¹I]NaI not being found among the interactions.

According to different documents available from the National Health Service of the United Kingdom and the Centers for Disease Control and Prevention of the United States, the reason why these two types of therapy with radiopharmaceuticals are included is the possibility of immunosuppression with these treatments. Although the administration of vaccines with inactivated virus or a non-infectious vaccine is generally safe in immunosuppressed patients, this condition may carry less immunological response (suboptimal response) to the vaccine. To minimize this possibility it is recommended to space out the treatment a minimum of two weeks (Immunization Against Infectious Disease – “The Green Book”. Chapter 6: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/655225/Greenbook_chap; Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States: https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html#Coadministration; General Best Practice Guidelines for Immunization: Altered Immunocompetence: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.pdf).

On the other hand, treatment with radioiodine for thyroid disease (hyperthyroidism or differentiated thyroid cancer) does not seem to interfere with the immunological response of the vaccine.

The American Thyroid Association (https://www.thyroid.org/covid-19), the European Thyroid Association (https://www.eurothyroid.com/news/covid-19-vaccination-thyroid-disease.html) and the European Society of Endocrinology (https://www.ese-hormones.org/about-us/our-communities/clinicians/covid-19-and-endocrine-disease), recommend the administration of the vaccine to all patients with thyroid diseases such as autoimmune disease (Hashimoto thyroiditis, Graves-Basedow disease) or thyroid cancer, if they are clinically stable. The recommendations specifically advise against the delay of treatment with radiopharmaceuticals, although treatment planning should be discussed with the attending physician.

In relation to the treatment of differentiated thyroid cancer with radioiodine, a thyroid-stimulating hormone (TSH) value >30 IU/mL is required for being effective. This rate can be achieved by stimulation with recombinant TSH (Thyrogen®) or by withdrawal of hormone replacement medication (levothyroxine) during 4 weeks, producing transitory hypothyroidism. At present, there are no publications in the scientific literature regarding interactions between Thyrogen® and the SARS-CoV-2 vaccine or between the induction of hypothyroidism and the effectiveness of the vaccine. Neither has there been any update on the precautions of adverse effects in the official Summary of Product Characteristics of the drug published by the Spanish Agency of Medication and Health Care Products. Moreover, professionals from Sanofi España reported no interactions between Thyrogen® and the vaccine, thereby recommending vaccination according to the official vaccination calendar of each region.

Other interactions and recommendations:

An autoimmune/inflammatory syndrome induced by adjuvants of the vaccines (known as ASIA) was described a decade ago in relation to clinical manifestations derived from the potentiation of the immune system provoked by some vaccines and mainly associated with the human papilloma virus, influenza and hepatitis B³. The development of Graves disease is among the spectrum of possible clinical presentations⁴.

Recently, in May 2021, the journal “Thyroid” (official publication of the American Thyroid Association), described 2 cases of Graves disease after the administration of the Pfizer-BioNTech vaccine. In these two cases, the clinical manifestations of hyperthyroidism occurred 2–3 days after administration of the vaccine. Therefore, it is recommended to include the history of vaccination against SARS-CoV-2 when considering treatment with radioiodine in patients referred for hyperthyroidism⁵.

To conclude, it is recommended to evaluate each individual case with respect to the treatment to be performed and the type of radiopharmaceutical, considering possible adverse effects and the dose to administer. If there is the possibility of the treatment causing immunosuppressive effects, which could induce suboptimal response to vaccination, it is recommended to space the treatment with radiopharmaceuticals by at least two weeks after the administration of the vaccine.