Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan in December 2019. On March 11, 2020, the World Health Organization (WHO) declared a global pandemic, and outbreaks across the world have caused an enormous burden on healthcare systems. There have been more than 430 million cases and 5.92 million deaths reported worldwide as of February 25, 2022.¹ Over the last 2 years, the virus has mutated several times, resulting in increased morbidity and mortality amidst different waves of emerging variants.² Following Alpha, Beta, Gamma, and Delta variants, the highly mutated Omicron (B.1.1.529) variant emerged in November 2021 and spread rapidly worldwide due to its high transmissibility.

In December 2020, after less than 1 year of development, messenger RNA (mRNA) vaccines Comirnaty (Pfizer/BioNTech) and Spikevax (Moderna) were given approval for use after their success in phase 3 trials. These trials demonstrated more than 90% efficacy in preventing severe disease and few side effects.^{3, 4} In addition to administering vaccines, countries around the world implemented their own public health measures, such as increased testing rates, school closures, and face-covering requirements.⁵ While various therapies have been approved for use to reduce the severity of disease in patients already infected with COVID-19,⁵ significant resources have been devoted to vaccine development.

A high level of community vaccination has been crucial in combating the global pandemic; however, COVID-19 vaccines have been associated with various side effects, including headache, muscle pain, fevers, and injection-site reactions. Furthermore, there has been recent concern about the link between mRNA vaccines and the flaring or development of immune-mediated disease complications, such as myocarditis/pericarditis, in patients with autoimmune inflammatory rheumatic diseases (AIRD).⁶ In this brief report, we describe three patients with pre-existing AIRD who developed myocarditis or pericarditis shortly after receiving their first dose of the Pfizer-BioNTech vaccine.

The first case is of a 31-year-old female with a history of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APLS). Her serology and disease manifestations are summarized in Table 1. She had no other significant medical history. She was admitted to hospital 7 days after her first dose of the Pfizer/BioNTech vaccine in May 2021 with a 3-day history of worsening pleuritic chest pain, fevers, and shortness of breath (SOB). Her C-reactive protein (CRP) was elevated to 68 mg/L and her erythrocyte sedimentation rate (ESR) was also significantly elevated at 92 mm/h. Her high sensitivity troponin (hs-Trop) peaked at 159 mg/L. An electrocardiogram (ECG) was normal, however, a transthoracic echocardiogram (TTE) showed a small circumferential pericardial effusion of 0.3 cm (Table 2). The patient was diagnosed with myopericarditis and commenced on prednisolone 25 mg for 1 week, then weaned down to 5 mg over the subsequent 2 weeks. She was referred to the Victorian Specialist Immunisation Services (VicSIS), where she was advised to have the AstraZeneca/Oxford vaccine for her second dose, which she did without any adverse effects.

The second case is of a 29-year-old man with a history of seronegative inflammatory arthritis and APLS (Table 1) who presented to the emergency department (ED) with central chest pain, fatigue, and SOB 7 days post his first dose of the Pfizer/BioNTech vaccine in August 2021. His ECG showed widespread ST elevation. His CRP was 37 mg/L, ESR 50 mm/h, and hs-Trop <3 mg/L. He underwent a CT pulmonary angiogram (CTPA), which showed several left-sided subsegmental pulmonary emboli (PE). He was reviewed by a cardiologist who felt his presentation was more in keeping with pericarditis than an acute PE, and the CTPA findings were likely from the patient's previous deep vein thrombosis diagnosed 8 months prior. The patient's prednisolone was increased from 5 to 20 mg daily and his symptoms improved. He had an outpatient TTE, which was unremarkable. He was reviewed by his cardiologist 6 weeks after his presentation and they felt it was appropriate for him to proceed with his second dose of the Pfizer/BioNTech vaccine. The AstraZeneca/Oxford vaccine was contraindicated as he had a known thromboembolic event with triple antibody-positive APLS. The patient had the second Pfizer/BioNTech vaccine dose 7 weeks after his first dose; however, 2 days after, he again developed central pleuritic chest pain. The prednisolone dose at the time of his second vaccine was 7.5 mg daily. He self-increased his prednisolone to 15 mg daily, which resolved his symptoms. He was subsequently reviewed by his rheumatologist, who weaned the prednisolone over 2 weeks back down to the baseline dose of 5 mg daily.

The third and final case is of a 34-year-old man with Behcet's disease diagnosed after he developed recurrent episodes of pericarditis in 2020. The diagnosis of pericarditis was made on ECG, TTE (Table 2), and after a consultant cardiologist review. His disease manifestations and serology are summarized in Table 1. He had no other significant past medical history and his disease was well controlled with Colchicine 500 mcg twice daily. He received the first dose of the Pfizer/BioNTech vaccine in August 2021. Approximately 7 days later, he developed central pleuritic chest pain identical in nature to his previous episodes of pericarditis. The patient was reluctant to attend the ED so he commenced himself on 15 mg of prednisolone daily at home from a previously dispensed prescription. This rapidly improved his symptoms and he was reviewed by his rheumatologist the following week, who weaned his prednisolone to cessation over 2 weeks. A blood test was performed a week after his symptoms resolved and showed normal inflammatory markers (CRP of <1 mg/L and ESR 2 mm/h) likely due to the commencement of prednisolone the week prior. A hs-Trop, ECG, and TTE were not performed. He was referred to VicSIS and his presentation was felt to be in keeping with an acute episode of pericarditis. He was advised to have the AstraZeneca/Oxford vaccine for his second dose. He received the AstraZeneca/Oxford vaccine 6 weeks after the initial Pfizer/BioNTech vaccine. He had no adverse effects from the AstraZeneca/Oxford vaccine and is planned to receive this vaccine for his booster dose.

Myocarditis/pericarditis has been recognized as a rare side effect of mRNA COVID-19 vaccines in many countries, including Israel, the United Kingdom, Europe, Canada, and the United States. One of the largest studies is a retrospective study by Montgomery et al. looking at US military personnel vaccinated with mRNA vaccines. They found 23 cases (Pfizer, n = 7 cases; Moderna, n = 16 cases) of myocarditis out of 2.8 million recipients, yielding a rate of 8.21 per million persons. All 23 patients were fit and healthy males who developed chest pain and had markedly elevated troponin levels within 4 days postvaccination. Managed care was brief and all patients made a rapid recovery.⁷ Another study by Mevorach et al. looked at 5.1 million mRNA vaccine recipients and found 136 cases of suspected myocarditis, consistent with a rate of 26.7 per million persons. Of these, 95% were mild cases and only one case was fatal.⁸ In Australia, to January 2, 2022, the Therapeutic Goods Administration (TGA) reported 415 reports of likely myocarditis from 27.3 million doses of Pfizer/BioNTech and 40 reports of likely myocarditis from about 1.8 million doses of Moderna. This is an incidence of 14.3 per million doses administered.⁹

Studies have found that the risk of myocarditis and pericarditis is higher in young males after their second dose. Mevorach et al. showed that the incidence ratio of developing myocarditis after the second dose compared with the first doses was 1.76 overall and highest for male recipients aged 16–19 years at 13.73.⁸ Similarly, the Israeli Ministry of Health reported cases predominately in young men of less than 30 years, and those who had their second dose of vaccine within the preceding 3 days.¹⁰

While individuals with other pre-existing cardiovascular conditions are free to receive the mRNA COVID vaccines without specific precautions or specialist review, those with a history of current or recent myocarditis/pericarditis due to causes other than vaccination are advised to consult with a general practitioner, immunization specialist service or cardiologist as per the current Australian Technical Advisory Group on Immunisation (ATAGI) guidelines.¹¹ It should also be noted that Australian guidelines clearly state that mRNA vaccines provide overwhelming benefits against COVID-19 and its complications, compared with the rare risk of myocarditis/pericarditis after vaccination.¹¹

There has been concern from rheumatologic societies about the occurrence of symptomatic flares of AIRD following vaccination.⁶ The pathophysiology of vaccine-related myocarditis/pericarditis remains unknown. One hypothesis is that molecular mimicry causes a nonspecific inflammatory response due to antibody cross-reactivity.¹² Watad et al. reported on 27 patients who had AIRD flares or new disease onset following vaccination with an mRNA vaccine. Of these, there was one patient with SLE who developed pericarditis with associated pericardial and pleural effusions 4 days postvaccine and another with idiopathic pericarditis who developed pericarditis with fevers 2 days postvaccine. Both experienced a rapid response to therapy with quick symptom improvement.¹³ To date, there are few studies on the occurrence of pericarditis in individuals with pre-existing AIRDs.

The cases presented detail our experience with Pfizer/BioNTech vaccine-induced myopericarditis/pericarditis in three AIRD patients. In Australia, the main mRNA vaccine which has been used is the Pfizer/BioNTech. With the recent introduction of the Moderna vaccine, we will need to closely monitor our patients for side effects and disease flares. Many inflammatory rheumatological conditions predispose patients to develop inflammatory cardiac conditions; however, it is unclear if merely having a rheumatological condition puts the patient at increased risk of developing myopericarditis or pericarditis from an mRNA vaccine. Larger studies will need to be conducted to see if this risk is higher in AIRD patients. We will likely continue to need booster vaccines; therefore, it will be useful to have a framework to identify high-risk patients. These patients could be closely monitored for signs of cardiac complications or offered an alternative vaccine.

AUTHOR CONTRIBUTION

All authors contributed to preparation of this manuscript.

CONFLICTS OF INTEREST

The authors declare no conflict of interest. Keith Lim is Editorial Board member of Rheumatology & Autoimmunity. They were blinded from reviewing or making decisions on the manuscript. The article was subject to the journal's standard procedures, with peer-review handled independently of these Editorial Board and Editorial Office members and their research groups.