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Article

COVID-19-Vaccination-Induced Myocarditis in Teenagers: Case Series with Further Follow-Up

1
Department of Pediatric Cardiology and General Pediatrics, Medical University of Warsaw, 02-091 Warsaw, Poland
2
Department of Pediatric Radiology, Medical University of Warsaw, 02-091 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2022, 19(6), 3456; https://doi.org/10.3390/ijerph19063456
Submission received: 20 January 2022 / Revised: 6 March 2022 / Accepted: 11 March 2022 / Published: 15 March 2022

Abstract

:
Presently, the whole globe is struggling the tough challenge of the COVID-19 pandemic. Vaccination remains the most effective and safe COVID-19 weapon for adults and in the paediatric population. Aside from possible mild and moderate post-vaccination side effects, more severe side effects may occur. We retrospectively analysed a group of 5 teenagers aged from 15 to 17 years with obesity/overweight (BMI ranging from 24.8 to 30) who presented typical myocarditis symptoms following the first or second dose (3 and 2 patients, respectively) of the COVID-19 vaccine. In the whole study group, a significant increase in troponin serum concentration was observed (1674–37,279.6 ng/L) with a further quick reduction within 3–4 days. In all patients, ST segments elevation or depression with repolarisation time abnormalities in electrocardiography were noticed. Chest X-ray results were within normal limits. Echocardiography showed normal left ventricular diameter (47–56.2 mm) with ejection fraction between 61–72%. All patients were diagnosed with myocarditis based on cardiac magnetic resonance (CMR) imaging. During further hospitalisation, swift clinical improvement was notable. Follow-up in the whole study group was obtained after 106–134 days from initial CMR, revealing no myocarditis symptoms, proper troponin level, and no ECG or echocardiographic abnormalities. At the same time, persistent myocardium injury features were detected in the whole study group, including ongoing myocarditis. COVID-19-vaccine-induced myocarditis seems to be a mild disease with fast clinical recovery, but the complete resolution of the inflammatory process may last over 3 months. Further follow-up and investigation for assessing subsequent implications and long-term COVID-19-vaccine-induced myocarditis is required.

1. Introduction

The worldwide spread of the coronavirus (COVID-19) pandemic has caused over 5 million deaths across the globe [1]. For the time being, in European countries, two messenger RNA (mRNA) vaccines (Pfizer-BioNTech and Moderna) are approved to reduce the risk, severity, and transmission of the COVID-19 disease in the 12–18 years age group [2]. Beyond mild and moderate post-vaccination side effects, more severe side effects, such as myocarditis, have also been noted [3]. According to the Vaccine Adverse Event Report System (VAERS), 691 cases of COVID-19 vaccine side effects, diagnosed as myocarditis in the aforementioned population, have been reported to date [4]. In our study, we present the clinical characteristics of 5 teenagers hospitalized in the Paediatric Cardiology Department of University Hospital due to acute myocarditis following Pfizer-BioNTech vaccination. Our studied group is one of the first and currently the biggest population with further long-term follow-up with particular emphasis on CMR imaging evaluation in the whole study group.

2. Materials and Methods

Our single-centre retrospective study comprised five teenagers hospitalized in the Paediatric Cardiology and General Paediatrics Department from July to August 2021 who were assessed by signs and clinical symptoms, laboratory data of cardiological biomarkers (troponin serum concentration and NT-proBNP), electrocardiography, echocardiography, and cardiac magnetic resonance (CMR). Follow-ups were carried out 106–134 days after initial CMR.

3. Results

All patients were white male teenagers (age range 15–17 years) with no underlying medical conditions on admission. Four patients were obese, and one was overweight, according to the World Health Organization’s body mass index [5]. None of them had a positive medical history for previous COVID-19 infection. All patients received the Pfizer-BioNTech mRNA vaccine, 3 of them developed symptoms after the first dose and 2 developed symptoms after the second dose. All presented with symptoms 2–8 days after immunization, with sudden onset sharp and retrosternal chest pain radiating to the left shoulder in patient 5. All but one (patient 4) had body temperature rise, one (patient 2) reported diarrhoea and shoulder pain at the injection spot, and one (patient 4) was affected with dry cough. Symptom duration ranged from 3 to 6 days (Table 1).
On admission, all patients were in a good condition with stable vitals. Each of them was tested for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR swab test with negative results in the whole group. Other viral and bacterial serologies testing included the most common respiratory tract, neurological, and digestive system pathogens, and were all negative. Blood tests revealed significant increases in highly sensitive troponin I serum concentration in all patients with further rapid, gradual normalization. Furthermore, moderate rise of N-terminal pro-B type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) plasma concentration was noticed in patients 1 and 4 and patients 1, 2, 3, and 5, respectively, with normalization above mentioned parameters before hospital discharge (Table 1).
Electrocardiogram (ECG) pattern varied, but in all cases, characteristic features for acute myocardium injury, including ST segments elevation or depression, and repolarisation time abnormalities were observed (Table 2). Chest X-rays in all patients revealed no abnormalities. In all patients, transthoracic echocardiography (TTE) showed normal size and function of the left ventricle to the left ventricular internal diameter in diastole (LVIDd) and ejection fraction (EF) within normal limits.
All patients underwent cardiovascular magnetic resonance imaging (CMR) between 6 and 37 days after vaccine immunisation to confirm and evaluate extend of nonischemic myocardium injury and oedema according to updated 2018 Lake Luise Myocarditis Criteria [6]. The obtained CMR images revealed hyperintense signal of oedema partly overlapping with late gadolinium enhancement (LGE) in particular LV segments and thus fulfilling Lake Louise Criteria for myocarditis in the whole group (Table 2). In all patients left and right ventricular function was within normal limits and no pericardial involvement was detected in either the ECHO or the CMR imaging. Considering good general condition with stable vitals, none of the patients qualified for endomyocardial biopsy.
During further hospitalization, all patients were treated with angiotensin-converting enzyme inhibitors (ACEI), and were discharged in stable clinical condition, with no alarming symptoms after 10–16 days of hospital observation and recommendation of a further 3-month follow-up.
Three months after hospital discharge (with the exception of patient 5 with follow-up appointment postponed for one month due to moderate infectious symptoms) renewed evaluation of general condition and additional tests were performed, revealing no symptoms similar to admission time in all except one (patient 4, who reported single, sharp episodes of chest pain lasting for few seconds), normal highly sensitive troponin I serum concentration, regular pattern of ECG in all but one (patient 3, preserved flat T wave in leads V5 and V6), no arrhythmias in 24 h Holter–ECG monitoring, and no abnormalities in TTE. All the patients at this point underwent control CMR (106–134 days after initial CMR). In contrast to other tests, in all patients, CMR imaging showed persistent features of myocardial injury: active inflammatory process (T2-weighted images of myocardium oedema coexisting with LGE in T1-weighted mapping patients 1 and 4) or persistent LGE without oedema. In all patients, ACEI treatment was continued and further treatment was planned (Table 3).

4. Discussion

Vaccination against COVID-19 undoubtedly remains the most effective and proved form of COVID-19 elimination in all population groups [7,8]. Moderna and Pfizer-BioNtech mRNA vaccines are distinguished by their high efficacy and safety in children [2,9]. It should be noted that COVID-19 immunisation carries the possibility of mild–moderate side effects (e.g., pain in injection site, fever, malaise occurring and resolving within 1–2 days). In rare cases, more severe adverse effects, even including life-threatening ones, such as myocarditis, may occur [3,10]. It is worth mentioning that post-vaccination myocarditis has been also widely reported after many other vaccines, including influenza, hepatitis B virus, and tetanus [11,12]. The strongest case–effect relation between immunisation and myocardium injury were proven for smallpox vaccination. Endomyocardial biopsy with further pathomorphology study in those cases showed immunological etiology rather than direct myocardium injury [13,14]. As can be seen from the available literature, COVID-19 infection may also provoke subsequent immoderate host immune response [15], so it is possible that, in some rare cases, the same mechanism may be triggered by vaccine administration. The direct mechanism of myocardium injury following the COVID-19 vaccine remains unclear and further investigations are needed [16].
In our study, with a homogeneous teenager group, four patients were described as obese, and one as overweight, according to the WHO body mass index. This may be considered an interesting fact in the light of the recent review by Bortolini et al., according to which, physical inactivity and obesity are factors decreasing the vaccine’s efficacy and immune response [17]. However, obesity itself is a known risk factor of hyperimmune reactions, which may be at least partially responsible for myocarditis in our group. Additionally, quick general condition and symptoms improvement correlated with rapid and prominent decrease in troponin I serum concentration was observed (within 3–4 days after peak, Table 1), and ECG normalization was observed within the whole group.
Similar patterns have been presented in the current literature. In most reported cases, myocarditis after COVID-19 immunisation affects male adolescents or young adults between 12 and 24 years, most commonly after the second dose of the mRNA-type vaccine [18]. The majority of patients presented typical myocarditis symptoms—chest pain, shortness of breath and, fever—within 2–4 days after administration and also with swift improvement of symptoms and general condition. Most patients did not require any advanced therapy or additional procedures [18,19,20,21].
In CMR, the location of myocardial lesions during the acute period (both LGE and oedema) was, in our group, similar to patterns reported so far in the literature (basal and mid-lateral segments of left ventricle) [22,23,24,25]. Despite of significant difference of peak troponin between patients 1, 2, and 3 and patients 4 and 5, there was no correlation between troponin level and CMR findings. The extend of myocarditis in all patients, estimated on the basis of myocarditis involved left ventricle segments, was comparable in all patients. Moreover, elevated troponin concentration, before the outbreak of the COVID-19 pandemic, was recognised as a poor prognostic marker in adult patients with acute coronary syndrome, as well as in children with acute fulminant myocarditis [26]. Contrarily, according to a retrospective by Matsubara et al., longitudinal cohort study troponin concentration seems to not be correlated with worse clinical implications in children with paediatric inflammatory multisystem syndrome temporary, associated with SARS-CoV-2 (PIMS-TS) [27]. In view of the above, and the supposed immune mechanism of PIMS-TS and COVID-19-vaccine-related myocarditis, the troponin level appears to not reflect the CMR findings in wither of the abovementioned groups. This issue still requires further analysis.
Interestingly, the mild and transient clinical course of the disease was not illustrated by the CMR results obtained after 3 months. In all our patients, persistent abnormalities were found, including an active inflammatory process in two of them. To our knowledge, this is one of the first publications highlighting this problem and, so far, the present study is based on the largest number of cases.
In August 2021, Supriya et al. described persistent CMR abnormalities (LGE without oedema) in 2 patients with myocarditis after COVID-19 vaccine in whom CMR was performed after 66 and 71 days from initial CMR [28].
In our group, the active inflammatory process lasted longer. In two patients, after three months, CMR showed persistent oedema with LGE, and in only three LGE.
On the other hand, the most current data from the literature suggest that children with acute myocarditis not related to the vaccination also show CMR abnormalities (mostly LGE) months after full clinical recovery. Seven months after the initial CMR, approximately one third of children still present CMR abnormalities suggestive of active inflammatory processes, and only one third can be described as exhibiting total normalization [29]. Moreover, about half of the patients after myocarditis recovery may present myocardium scarring (consistent with LGE in CMR), which could transform into the trigger spots for even life-threatening rhythm disturbances [30].
In view of the above, our study, with special emphasis on CMR imaging follow-up, symbolises one step forward in obtaining insights into the course and recovery pattern of COVID-19-vaccine-induced myocarditis. Both further studies and longer follow-up of patients should be considered to assess ensuing implications of COVID-19-vaccine-connected myocardium injury.

5. Conclusions

COVID-19-vaccine-induced myocarditis seems to be a mild disease with a fast clinical recovery.
The complete resolution of the inflammatory process may last longer.
Based on CMR findings in the study group, the myocardium injury may persist longer than three months from the initial CMR.
Longer follow-up and further investigation for assessing subsequent implications and long-term COVID-19-vaccine-induced myocarditis are required.

Author Contributions

Conceptualization, B.W. and M.P.; data curation, M.P., M.B. (Marta Bartoszek) and M.B. (Michał Brzewski); formal analysis, M.P., H.K. and B.W.; writing—original draft preparation, M.P.; writing—review and editing, B.W., H.K., M.P. and M.B. (Michał Brzewski); supervision, B.W. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical review and approval were waived due to the retrospective nature of the study basing on already available data.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data will be made available by the corresponding author, upon reasonable request.

Conflicts of Interest

Authors declare no conflict of interest.

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Table 1. General information, laboratory tests, treatment, length of hospital stays.
Table 1. General information, laboratory tests, treatment, length of hospital stays.
Case 1Case 2Case 3Case 4Case 5
SexMMMMM
Age1517171717
BMI kg/m2 (WHO centiles)27 (95), obesity25.8 (95), obesity30 (97), obesity30 (99), obesity24.8 (89), overweight
Vaccine namePfizer-BioNTechPfizer-BioNTechPfizer-BioNTechPfizer-BioNTechPfizer-BioNTech
Dose number22111
Time (days) from vaccine to symptoms 222323
Symptom descriptionCentral, non-radiating chest pain, fever (37.8), Central, non-radiating chest pain, fever (38.5), shoulder pain at the injection site, diarrhoeaLeft-sided, non-radiating chest pain, fever (39), dry cough,Left-sided, non-radiating chest painCentral, radiating to the left shoulder chest pain, sore throat, fever (39)
Symptom duration (days)33446
Laboratory tests:
COVID-19 PCR test at presentationNegativeNegativeNegativeNegativeNegative
COVID-19 antibodies
IgA and IgM classNegativeNegativePositivePositiveNegative
IgG classPositivePositivePositivePositive Positive
Troponin concentration
Peak14,218.437,279.610,450.31895.21674
Next troponin level (days after peak)102 (4)354.1 (3)327.0 (3)325 (3)360.0 (3)
Discharge (days after peak)12.4 (9)20.9 (13)18.5 (14)8.5 (12)1.5 (11)
Others:
NT-proBNP2692750259391
CRP3.03.93.90.740
White blood cell count6.810.027.788.029.95
Viral and bacterial serological tests
Respiratory tract panel 1Negative NegativeNegativeNegativeNegative
Neurological panel 2NegativeNegativeNegativeNegativeNegative
Rotavirus and adenovirusNot obtainedNegativeNegativeNegativeNegative
TreatmentLisinoprilEnalaprilRamiprilRamiprilRamipril
Length of hospital stay (days)1013161211
NT-proBNP, pq/mL, (N < 125); Troponin, ng/L (N < 19.0); CRP mg/dL, (N: 0.0–1.0); White blood cell count (N: 4–10 × 103/uL). 1 Respiratory tract panel—nasopharyngeal swab; PCR testing—adenovirus, mycoplasma pneumoniae, coronaviruses (HKU1, NL63, OC43, 229E), human metapneumovirus, human rhino/enterovirus, influenzas viruses (A, A/H1, A/H1-2009, A/H3, B, MERS), parainfluenza viruses (1, 2, 3, 4), RSV, SARS-CoV-2, Bordetella pertussis, Bordetella parapertusis, Chlamydophila pneumoniae. 2 Neurological panel, blood sample PCR testing—CMV, EBV, HSV1, HSV2, HSV6, HHV6, HHV7, Enterovirus, Adenovirus, Parechovirus, Parvovirus, ParvovirusB19.
Table 2. Imaging tests.
Table 2. Imaging tests.
Case 1Case 2Case 3Case 4Case 5
Imaging Tests
Chest X-rayUnchangedUnchangedUnchangedUnchangedUnchanged
ElectrocardiogramST elevation in I, II, V5–V6, ST elevation in II, III, aVF, V5–V6 ST elevation in V3–V4ST elevation in II, III, aVFST elevation in V4–V6
ST depression in V1–V2 Negative T wave in I–III, aVL, aVF, V4–V6,
Echocardiography
%EF6472616268
Left Ventricular End Diastolic Diameter (mm)54.547–5045.956.255
Regional wall motion changes and pericardial effusionNo changesNo changesNo changesNo changesNo changes
CMR imaging
Time from vaccine to CMR (days)86101137
Myocardial oedema (T2 mapping), segment of LVAll basals All basals,Mid: inferior and inferolateralAll basalsAll basals
Mid: anterolateral, inferolateralMid: anterolateral, inferolateral, Mid: inferior, inferolateralMid: inferior, inferolateral
inferoapical: lateral and inferior Apical: inferior, lateral
Nonischemic Myocardial Injury (LGE, T1-weight mapping)
Subepicardial and intraventricular LGE in segmentsBasal: anterolateral, inferolateral, inferiorAll basalsNo changesNo changesAll basals,
Mid: inferolateral, inferiorsMid: inferolateral
Apical: inferior and lateral
Only subepicardial LGE in segmentsMid: anterolateral, inferolateralAll basalsBasal: inferior and inferolateralAll basalsAll basals
Mid: anterolateralMid: inferior, inferolateralMid: anterolateral
Apical: inferior and lateral
Troponin, ng/L (N < 19.0).
Table 3. Follow-up 106–134 days from initial CMR.
Table 3. Follow-up 106–134 days from initial CMR.
Follow-Up
Case 1Case 2Case 3Case 4Case 5
Follow-Up
Troponin, ng/L (<19.0)4.71.5<1.52.3Not obtained
ECG findingsNo changesNo changesFlat T wave in V5–V6No changesNo changes
Echocardiography
%Ejection Fraction6166776677
Regional wall motion changesNo changesNo changes No changesNo changesNo changes
Pericardial effusionNo changesNo changesNo changesNo changesNo changes
CMR imaging
Time from initial CMR (days)106119112112134
Myocardial oedema (T2 mapping), segment of LVAll basalsNo oedemaNo oedemaBasal inferolateralNo oedema
Mid: anterolateral, inferolateral
All inferior
Nonischemic Myocardial Injury (Late gadolinium enhancement LGE)
Subepicardial and intraventricular LGE in segments:Basal: anterolateral, inferolateral, inferiorAll basals,No changesNo changesAll basals
Mid: inferolateral,Mid: inferolateral, inferior
All inferior
Apical lateral
Only subepicardial LGE in segments:No changesNo changesBasal: inferior and inferolateralAll basalsNo changes
Mid: inferior, inferolateral
Apical: inferior, lateral
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Puchalski, M.; Kamińska, H.; Bartoszek, M.; Brzewski, M.; Werner, B. COVID-19-Vaccination-Induced Myocarditis in Teenagers: Case Series with Further Follow-Up. Int. J. Environ. Res. Public Health 2022, 19, 3456. https://doi.org/10.3390/ijerph19063456

AMA Style

Puchalski M, Kamińska H, Bartoszek M, Brzewski M, Werner B. COVID-19-Vaccination-Induced Myocarditis in Teenagers: Case Series with Further Follow-Up. International Journal of Environmental Research and Public Health. 2022; 19(6):3456. https://doi.org/10.3390/ijerph19063456

Chicago/Turabian Style

Puchalski, Mateusz, Halszka Kamińska, Marta Bartoszek, Michał Brzewski, and Bożena Werner. 2022. "COVID-19-Vaccination-Induced Myocarditis in Teenagers: Case Series with Further Follow-Up" International Journal of Environmental Research and Public Health 19, no. 6: 3456. https://doi.org/10.3390/ijerph19063456

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