Myocarditis development after COVID-19 vaccination in an immunodeficient case

Dear Editor,

It is thought that the coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), can be controlled globally by the administration of vaccines. Although COVID-19 primarily affects the respiratory system, systemic effects are also seen in the clinic. Cardiac complications of the disease caused by SARS-CoV-2, in particular, can be life-threatening [1]. The COVID-19 mortality rate due to cardiovascular problems is estimated at 10.5% [2].

In this article, an immunodeficient case who presented with chest pain after the third dose of the Pfizer-BioNTech® mRNA vaccine against SARS-CoV-2 is discussed.

A seventeen-year-old male patient was diagnosed with common variable immunodeficiency (CVID) and followed up in the pediatric immunology division. He presented with chest pain three days after the third dose of the Pfizer-BioNTech® vaccine. In his physical examination, no organomegaly was detected. His-lung sounds were normal. The rest of his physical examination was unremarkable at that time as well. Routine biochemistry and hemogram values were also within normal limits. His-thorax CT showed normal findings in the last year. During this time he was receiving intravenous immunoglobulin (IVIG) therapy at the dose of 0.5 g/kg/month. The frequency of infections was very rare in the last few years. He suffered from just a couple of uncomplicated upper respiratory tract infections. During this period his serum immunoglobulin (Ig) levels were as follows: IgG 1560 mg/dl, IgA 6,0 mg/dl, and IgM 66 mg/dl. Troponin level was 20,657 ng/L, myoglobin was 429 mcg/L, and C-Reactive protein (CRP) was measured as 40 mg/L. The patient's echocardiography (ECHO) was unremarkable as well. The first electrocardiogram (ECG) was normal. He was hospitalized for follow-up. T negativity was observed in the leads of V5 and V6 in the control ECG (Fig. 1 ). T1 mapping of cardiac magnetic resonance imaging (MRI) was normal. The patient, whose complaints lessened and troponin level decreased to 43 ng/L, was discharged. It was learned that the patient did not have chest pain in the outpatient clinic follow-up. At the last follow-up, the troponin level was measured as 8 ng/L.

Fig. 1.

T negativity is seen in the leads of V5 and V6 of control ECG.

Myocarditis is an inflammatory injury of myocardial tissue without ischemia. The most common cause is a viral infection [3]. It is usually a mild illness characterized by chest pain, shortness of breath, or tachycardia [4]. Left ventricular dysfunction is associated with a poor prognosis when arrhythmia and heart failure complications develop [3]. The pathogenesis of SARS-CoV-2-related heart disease has not yet been elucidated. The most common mechanisms are cytokine storm and angiotensin-converting enzyme-2 (ACE-2) mediated heart damage due to SARS-CoV-2 infection [3,5].

Kuntz et al. [6] considered the presence of at least two of the following criteria as definitive myocarditis in patients with post-vaccination with elevated cardiac enzymes or evidence of myocardial inflammation. These criteria are dyspnea, palpitations, or chest pain; ECG abnormalities or left ventricular dysfunction. Accordingly, our patient can be considered to have had myocarditis because he meets these conditions.

The increase in troponin that occurs during SARS-CoV-2 infection is an indicator of hyperinflammation. It may indicate myocardial damage and acute myocarditis due to SARS-CoV-2 [5]. Similarly, some myocarditis cases have been reported in the literature after COVID-19 vaccines. The peculiarity of our point is that he was a patient with a diagnosis of CVID, and this occurred at the third, repeated dose of the mRNA vaccine.

According to the Israeli Ministry of Health data, between December 2020 and May 2021, 5.4 million people were vaccinated with Pfizer BioNTech, 27 cases were reported to have myocarditis at the first dose in 5.4 million people, and 121 cases were reported after the second dose in 5 million people. Most of them consisted of male cases between the ages of 16–19. The mean hospital stay of the patients was four days and 95% were reported as mild cases [4].

Montgomery et al. [7] reported that myocarditis developed in 23 male patients within 4 days after 2.8 million mRNA vaccination in a retrospective case series. All patients were given supportive treatments, and all showed improvement. All patients had chest pain and high troponin levels. Symptoms developed 12–96 h after the mRNA vaccine. Findings developed after the first dose in 3 patients and after the second dose in other patients. The median age range was 25. There were abnormal ECG findings in 83% of the cases. These are ST elevation and T wave inversions. Echocardiograms of 19 cases with abnormal ECG were normal. Coronary artery imaging was performed in 16 of them with computed tomography or cardiac catheterization. None of them had coronary artery disease. Kim et al. [8] reported 4 cases of myocarditis in the first five days after mRNA vaccination. All cases had chest pain and myocardial biomarkers. Cases were confirmed by magnetic resonance imaging (MRI) specific to myocarditis. Castiello et al. [5] emphasized in a systematic review that the increase in troponin is an indicator of myocardial damage. They also reported that the echocardiography results of 7 cases, diagnosed with COVID-19 and possible myocarditis, were normal. Tschöpe et al. [3] suggested the endomyocardial biopsy method for cases that could not be detected by cardiac MRI. Although cardiac MRI was normal in our patient, he had chest pain and elevated myocardial biomarkers including ECG 3 days after vaccination, similar to the literature.

Hagin et al. [9] administered the second dose of the Pfizer-BioNTech COVID-19 vaccine to 26 patients with immunodeficiency. Adverse events were recorded as pain at the injection site in 9 cases, fever in 3 cases, and axillary lymphadenopathy in 1 patient. No long-term side effects were observed in any of them. Göschl et al. [10] administered two doses of vaccination to 26 patients with immunodeficiency. They reported that no adverse event developed except fever and local reactions. Arroyo et al. [11] administered two doses of mRNA vaccines (11 BioNTech and 6 mRNA-1273) to 17 CVID patients and two doses of viral vector vaccine ChAdOx1 to 1 patient. There were no severe side effects after the vaccines. Fifty percent of CVID patients induced a cellular immune response at the first dose of the vaccine. The rate of immune response after the second vaccination was 83%. Cellular and humoral vaccine responses were significantly lower compared to healthy volunteers. Cases were observed for 3 months after vaccination, and no serious adverse events were reported. Similarly, there are studies in the literature that administered 2 doses of the COVID-19 vaccine to CVID patients and wrote positive vaccine responses and no serious adverse effects [9,12]. Similarly; in our reported limited experience with 20 patients, both inactivated virus Sinovac® and mRNA BioNTech® vaccine applications in our CVID patients seemed to be safe and reliable [13]. We think that it was an accidental not causal finding (complication), although we cannot fully explain the development of myocarditis seen only in this patient, which is not seen in our other CVID patients.

Immunocompromised patients are at high risk for SARS-CoV-2 infection. Vaccination is the most crucial measure to combat the epidemic and reduce the disease burden. COVID-19 disease is recognized as a cause of heart damage. Myocarditis and other adverse events developing after the COVID-19 vaccination should be carefully monitored. Clinicians should have informed about adverse conditions after immunization and should be able to perform symptomatic treatment and follow-up of patients. Such side effects should not diminish confidence in the value of vaccines.

Declaration of Competing Interest

None.