What do case reports say about the incidence of myocarditis following mRNA COVID-19 vaccination in adults and adolescent males?

Comment by InpharmD Researcher

There may be a possibility of an association between mRNA COVID-19 vaccination and acute myocarditis. However, the data presented in the case reports is not definitive. Overall, incidence rate of myocarditis and myopericarditis after COVID-19 mRNA vaccination cannot be accurately determined. Given that further studies are needed for strong, conclusive evidence, it is encouraged for patients to get the vaccination as benefits may outweigh risk.

Background

Since April 2021, increased cases of myocarditis and pericarditis have been reported in the United States after mRNA COVID-19 vaccination (Pfizer-BioNTech and Moderna), particularly in adolescents and young adults. There has not been a similar reporting pattern observed after receipt of the Janssen COVID-19 Vaccine (Johnson & Johnson). [1]

In most cases, patients who presented for medical care have responded well to medications and rest and had prompt improvement of symptoms. Reported cases have occurred predominantly in male adolescents and young adults 16 years of age and older. Onset was typically within several days after mRNA COVID-19 vaccination, and cases have occurred more often after the second dose than the first dose. CDC and its partners are investigating these reports of myocarditis and pericarditis following mRNA COVID-19 vaccination. The CDC continues to recommend COVID-19 vaccination for everyone 12 years of age and older given. [1]

The Centers for Disease Control and Prevention (CDC) states, "cases of myocarditis and pericarditis in adolescents and young adults have been reported more often after getting the second dose than after the first dose of one of these two mRNA COVID-19 vaccines. These reports are rare and the known and potential benefits of COVID-19 vaccination outweigh the known and potential risks, including the possible risk of myocarditis or pericarditis." [2]

On June 23rd, 2021, the following statement was co-signed by the U.S. Department of Health and Human Services (HHS), Centers for Disease Control and Prevention (CDC), American Academy of Family Physicians (AAFP), American Academy of Pediatrics (AAP), American College of Obstetricians and Gynecologists (ACOG), American College of Physicians (ACP), American Heart Association, American Hospital Association (AHA), American Medical Association (AMA), American Nurses Association (ANA), American Public Health Association (APHA), Association of Public Health Laboratories, Association of State and Territorial Health Officials (ASTHO), Big Cities Health Coalition, Council of State and Territorial Epidemiologists, Infectious Diseases Society of America, and National Association of County and City Health Officials (NACCHO):

“The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination. Importantly, for the young people who do [become infected], most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.” [3]

According to the new update from the Advisory Committee on Immunization Practices (ACIP) published earlier July 9, 2021, the panel has noticed an elevated risk of myocarditis, particularly among males aged 12-29 years after receiving mRNA COVID-19 vaccines. After reviewing reported cases of myocarditis and pericarditis, on June 23, 2021, ACIP states the benefits of receiving mRNA COVID-19 vaccines apparently outweigh the risks in adolescents and young adults. Accordingly, the Emergency Use Authorization (EUA) also reflects the information on myocarditis for public awareness. [4]

Among patients <30 years with reported myocarditis during May 1 – June 11, 2021, 323 of the 484 cases were determined to meet CDC's criteria of myocarditis, pericarditis, or myopericarditis based on provider interview and chart-review of the medical records. The median age of these confirmed cases was 19 (range, 12−29), and 291 (90.1%) of them were male. From vaccination to symptom onset, the median interval was two days (range, 0-40 days), and 309 (96%) were hospitalized for further management. By the time of case review, 95% of the patients had been discharged after mainly receiving conservative treatment, such as nonsteroidal anti-inflammatory drugs. Continuous follow-up is warranted to investigate long-term effects of myocarditis after receiving COVID-19 vaccines. Utilizing VAERS data with onset within seven days after dose 2 of an mRNA vaccine administered to males 12-29 years old, myocarditis reporting rates were 40.6 cases per million. The reporting rate was 62.8 myocarditis cases per million-second doses of mRNA COVID-19 vaccine administered among adolescents aged 12−17. In conclusion, ACIP emphasized the benefits over risks in this particular patient population, and the need to monitor and disseminate the information among the public and providers. [4]

Per the vaccine adverse effects reporting system (VAERS) database on July 27th, 2021, there have been 351 reports of myocarditis in pediatric patients. The majority have been associated with Pfizer (n = 347). [5]

The rate of myocarditis after the vaccination is potentially lower than in children who become infected. A cross‐sectional study included all children ≤18 years diagnosed with microbiologically confirmed (PCR analysis on nasopharyngeal swab) COVID‐19 (through a nasopharyngeal swab from March 2020 to October 2020; N= 129; mean age of 11 ± 4.4 years, 62 (48.1%) female). During the acute COVID‐19, 33 children (25.6%) were asymptomatic, and 96 (74.4%) had symptoms. Overall, 6 (4.7%) children were hospitalized, and 3 (2.3%) needed pediatric intensive care unit admission. After the initial diagnosis of COVID‐19, three developed multisystem inflammatory syndrome (2.3%) and two myocarditis (1.6%). [6]

References:

1. Centers for Disease Control and Prevention. Clinical Considerations: Myocarditis and Pericarditis after Receipt of mRNA COVID-19 Vaccines Among Adolescents and Young Adults. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html. Updated August 23, 2021.

2. Centers for Disease Control and Prevention. COVID-19 Vaccination [Internet]. Centers for Disease Control and Prevention. 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/adolescents.html

3. Statement following CDC ACIP meeting from nation’s leading doctors, nurses and public health leaders on benefits of vaccination [Internet]. [cited 2021 Jul 27]. Available from: http://services.aap.org/en/news-room/news-releases/aap/2021/statement-following-cdc-acip-meeting-from-nations-leading-doctors-nurses-and-public-health-leaders/

4. Gargano JW, Wallace M, Hadler SC, et al. Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee on Immunization Practices - United States, June 2021. MMWR Morb Mortal Wkly Rep. 2021;70(27):977-982. Published 2021 Jul 9. doi:10.15585/mmwr.mm7027e2

5. United States Department of Health and Human Services (DHHS), Public Health Service (PHS), Centers for Disease Control (CDC) / Food and Drug Administration (FDA), Vaccine Adverse Event Reporting System (VAERS) 1990 - 07/16/2021, CDC WONDER On-line Database. Accessed at http://wonder.cdc.gov/vaers.html on Jul 27, 2021 3:07:33 PM

6. Buonsenso D, Munblit D, De Rose C, et al. Preliminary evidence on long COVID in children. Acta Paediatr. 2021;110(7):2208-2211. doi:10.1111/apa.15870
Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

What do case reports say about the incidence of myocarditis following mRNA COVID-19 vaccination in adults and adolescent males?

Please see Tables 1-4 for your response.

 

Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination

Design

Case report

Case Presentation

 Characteristics of Patients Who Received COVID-19 Vaccination  

Characteristics

 Patient 1 Patient 2 Patient 3 Patient 4

Age, years

36

 23  70  24 

Sex

Male

 Male  Female Male

Comorbidities

Hypertension

Diabetes

Hypercholesterolemia

Cigarette smoking

History of CAD or MI

Prior myocarditis

Prior COVID-19 infection

  

No

No

No

No

No

No

No

  

No

No

No

No

No

No

No

  

Yes

No

Yes

Yes

No

No

No

  

No

No

No

No

No

No

No

Vaccine received

Doses received

mRNA-1273

2

BNT162b2

2

mRNA-1273

2

BNT162b2

2

Symptoms prior to vaccination (last dose)

Viral prodrome

        

Symptoms within 24 h of vaccination

Injection site discomfort

Fatigue/muscle ache

Fever/chills

Headache

Nausea

Chest pain

 

Yes

Yes

Yes

No

No

No

 

Yes

Yes

Yes

No

No

No

 

No

No

No

No

No

Yes

 

Yes

Yes

Yes

Yes

No

No

Hospitalization

Interval after vaccination, days

 

3

 

5

 

1 

 

2 

Symptoms leading to hospitalization

Severe chest pain (<12 h of hospitalization)

Shortness of breath

Diaphoresis

Syncope/presyncope

Palpitations

 

Yes 

Yes

No

No

No

 

Yes 

Yes

No

Yes

No

 

Yes 

Yes

Yes

No

No

 

Yes 

No

No

No

Yes

Severe chest pain

 Yes Yes  Yes Yes 
In-hospital testing        
Electrocardiogram Diffuse ST elevation; PR depression  Lateral; ST elevation Anterolateral; ST elevation Diffuse ST elevation: PR depression
Peak troponin, ng/L  hs-Tn T: 230 (abnormal) hs-Tn I: 7452 (abnormal) Tn I: 2.34 (abnormal) hs-Tn T: 698 (abnormal)

CPR, mg/dL

ESR, mm/h

ProBNP, pg/mL

WBC, /uL

COVID-19 testing

Respiratory virus PCR

Chest radiography

Chest CT

Coronary angiography

6.32 (abnormal)

6

NP

10,200

Negative

Negative

Normal

Negative for PE

NP

2.2 (abnormal)

30 (abnormal)

780 (abnormal)

10,800

Negative

Negative

Normal

Negative for PE

NP

Not performed (NP)

NP

5,194 (abnormal)

16,700 (abnormal)

NP

NP

Normal

NP

Normal coronaries

6.08 (abnormal)

12

65

13,500 (abnormal)

Negative

NP

Normal

NP

NP

Cardiac MRI

Interval after vaccination, days

LVEF,% 

Regional wall motion abnormality

Pericardial effusion

Pericardial thickness

 

3

53

Yes

Trace

Normal

  

5

58

Yes

Small

Normal

  

3

40

Yes

Small

Normal

  

3

59

Yes

Trace

Normal

LEG present

Location

Myocardial pattern

Pericardial enhancement

Yes

Apical lateral

Epicardial

No

Yes

Multiple

Epicardial

No

Yes

Multiple

Patchy, diffuse

No

Yes

Lateral

Epicardial, patchy

No

Therapy

Corticosteroids

Colchicine

NSAIDs

 

No

Yes

Yes

 

Yes

Yes

No

 

No

No

No

 

No 

Yes

Yes

Abbreviations: CAD, coronary artery disease; CRP, C-reactive protein; CT, computed tomography; ESR, erythrocyte sedimentation rate; hs-Tn, high-sensitivity troponin; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; MI myocardial infarction; MRI, magnetic resonance imaging; NSAIDs, nonsteroidal anti-inflammatory drugs; PCR, polymerase chain reaction; PE, pulmonary emboli; proBNP, pro-brain-type natriuretic peptide; WBC, whit blood cell count

Study Author Conclusions

In this study of 7 identified patients with acute myocarditis, 4 occurred within 5 days of COVID-19 vaccination between February 1 and April 30, 2021. All 4 patients had received the second dose of a messenger RNA (mRNA) vaccine, presented with severe chest pain, had biomarker evidence of myocardial injury, were hospitalized, and had cardiac magnetic resonance imaging findings typical of myocarditis.

Several caveats should be considered. First, there is no control group, and it is not possible to compare rates of acute myocarditis between those randomly assigned to receive vaccination vs no vaccination. Second, given the media attention, there could be recall or referral bias after COVID-19 vaccination compared with other vaccine exposures, and any temporal link between vaccination and myocarditis could just be due to chance. Third, although tests for COVID-19 infection and respiratory viruses were undertaken in some of the patients, these tests are neither foolproof nor comprehensive. Finally, there is no serological data, which could provide evidence of an excessive response to vaccination or prior subclinical COVID-19 infection (as determined by antinucleocapsid antibodies).

The findings from the present report raise the possibility of an association between mRNA COVID-19 vaccination and acute myocarditis. 



References:

Kim HW, Jenista ER, Wendell DC, et al. Patients with acute myocarditis following mRNA COVID-19 vaccination. JAMA Cardiol. 2021:e212828. doi: 10.1001/jamacardio.2021.2828.

 

Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination 

Design

Case report

Case Presentation

 Demographic and Clinical Characteristics of 7 Cases of Symptomatic Myocarditis After Dose 2 of Pfizer-BioNTech COVID-19 Vaccine 

 

Patient 1

Patient 2

 Patient 3 Patient 4 Patient 5  Patient 6  Patient 7

Age, years

 16 19  17 18 17 16 14

Sex

 Male Male Male  Male Male Male Male

Race

 White White White White White White White

Weight, kg

 68 68 71 69 64 71 92
Exposure to COVID-19 in 14 d before illness onset None  None   None  None  None  None  None 
Time between vaccine dose 2 and symptoms onset, days 2 3 2 2 4 3 2
Total hospital LOS, days 6 2 2 4 5 3 4
ICU LOS, days 4 None None 4 5 2 2
Symptoms on presentation
Chest pain Present Present Present Present Present Present Present
Other pain Bilateral arm pain Myalgia Bilateral arm pain, numbness, paresthesia -- Bilateral arm pain, abdominal pain -- --
Fever 38.3C by history Subjective, chills -- Subjective Subjective -- 38.3C by history
Fatigue Present Present -- Present -- -- --
Other Nausea, vomiting, anorexia, headache Weakness  -- Nausea Nausea, vomiting, anorexia, SOB, palpitations SOB SOB
Summary of Diagnostics and Therapeutics: 7 Cases of Symptomatic Myocarditis After Dose 2 of Pfizer-BioNTech COVID-19 Vaccine    
Laboratory findings on admission:
Troponin (normal range), ng/mL Troponin I: 2.59 (<0.03)  High-sensitivity troponin T: 232 (<14) Troponin I: 5.55 (<0.045) Troponin T:1.09 (<0.01) Troponin T: 3.2 (<0.01) Troponin T: 0.66 (<0.01) Troponin I: 22.1 (<0.045)
Brain natriuretic peptide (normal < 100), pg/mL -- -- -- -- -- -- 107.9
NT-proBNP (normal <125), pg/mL 428 -- 376 -- 978 149 --
Peripheral white blood cell count, thousands of cells per mm3 6.97 8.69 11.8 12.6 16.3 5.0 8.11
Absolute lymphocyte count, thousands of cells per mm3 1.69 1.39 2.13 2.3 4.1 1.4 1.05
Absolute neutrophil count, thousands of cells per mm3 4.65 5.93 7.46 9.5 9.8 2.8 4.73
Platelet count, thousands of cells per mm3 198 208 231 236 297 189 208
Albumin (g/dL) 3.9 4.1 4.1 4.4 4.0 3.8 3.5
Aspartate transaminase, U/L 54 29 41 82 150 59 87
Alanine transaminase, U/ 30  14 33 20 46 22 38
Ferritin, ug/L 70 -- 90 103 347 65 84
CRP (normal <1.0), mg/dL 0.99 6.7 2.5 12.7 18.1 1.5 7.7
ESR, mm/h 18 13 6 40 38 3 10
Prothrombin time, seconds -- -- 14.0 -- 12.1 11.4 14.8
Partial thromboplastin time, seconds 22.3 -- 31.4 -- 30.4 27.9 35.6
International normalized ratio INR 1.11  -- 1.06 -- 1.13 1.06 1.2
Other pertinent laboratory findings:
Highest troponin (normal range), ng/mL Troponin I: 12.43 (<0.80)  High-sensitivity troponin T: 388 (<14) Troponin I: 12.20 (<0.045) Troponin T: 1.09 (<0.01) Troponin T: 3.33 (<0.01) Troponin T: 0.82 (<0.01) Troponin I: 22.1 (<0.045)
Lowest troponin before discharge (normal range), ng/mL Troponin I: 1.42(<0.80) --  Troponin I: 5.79 (<0.045 Troponin T: 0.4 (<0.01) Troponin T: 0.96 (<0.01) Troponin T: 0.01 (<0.01) Troponin I: 8.02 (<0.045)
Highest BNP (normal range), pg/mL -- -- -- -- -- -- 205 (<100)
Highest NT-proBNP (normal range) 482 pg/mL (<125) -- 376 pg/mL (<300) -- 978 pg/mL (<125) 275 pg/mL (<125) --
Highest CRP (normal <1.0), mg/dL  1.23 6.7 2.53 12.7 18.1 1.8 12.7
COVID-19 PCR result Negative Negative Negative Negative Negative Negative Negative
COVID-19 spike antibody (manufacturer) -- -- Positive (Roche) Positive (Roche) Positive (Roche)  Positive (Roche)  --
COVID-19 nucleocapsid antibody result (manufacturer) Negative (Abbott) -- Negative (Roche) Negative (Roche) Negative (Roche) Negative (Roche) Negative (Abbott)
Respiratory pathogen panel PCR result (manufacturer) Negative (BioFire) Negative (BioFire) Negative (BioFire) Negative (BioFire) Negative (BioFire) Negative (BioFire) Negative (BioFire)
Adenovirus diagnostics result Negative serum PCR -- Negative serology Negative serum PCR Negative serum PCR -- Negative serum PCR
Enterovirus diagnostics result Negative serum PCR -- Negative serology Negative serum PCR Negative serum PCR Negative serum PCR Negative serum PCR
Cytomegalovirus diagnostics result Negative serum PCR -- Negative serology Negative serum PCR Negative serum PCR  Negative serum PCR Negative serology
Epstein-Barr virus diagnostics result     Negative serology Negative serum PCR  Negative serum PCR  Negative IgM, positive IgG antibody Negative serology 
Other diagnostics     Negative parvovirus, bartonella, and Lyme serology, negative urine drug screen --  Negative parvovirus and bartonella serology, negative HHV-6 serum PCR Negative Lyme serology, negative mycoplasma serum PCR, negative parvovirus serum PCR Negative parvovirus IgM, positive parvovirus IgG antibody, negative mycoplasma PCR (throat swab)
Diagnostic imaging findings: 
Cardiac MRI LGE (subepicardial) involving lateral LV apex, myocardial edema of lateral LV wall, left axillary adenopathy LGE involving mid LV wall, myocardial edema of basal inferolateral LV wall LGE (subepicardial) involving basal anterolateral and basal to midventricular inferolateral LV segments, myocardial edema, elevated extracellular volume fraction (29.2%) Fibrosis, myocardial edema, hyperemia, mild mitral regurgitation (RF ∼18%)  LGE (epicardial) involving anterior and lateral LV wall, no myocardial edema LGE, diffuse myocardial edema  LGE (subepicardial) involving mid and apical LV free wall, myocardial edema, hyperemia
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain Normal Normal Normal Mildly depressed RV and LV systolic function (LVEF 47%)
ECG Atrioventricular dissociation with junctional escape rhythm, ST elevation ST segment elevation (diffuse) ST elevation (diffuse), T-wave abnormality ST elevation Sinus bradycardia, T-wave abnormality  ST elevation (diffuse) ST elevation, low voltage of extremity leads 
Therapeutics:        
Oxygen supplementation None None None None None None LFNC
Vasoactive medications or inotropic support None None None None None None None
Antiinflammatory agents and other relevant medications NSAID, IVIg, IV methylprednisolone, PO prednisone, famotidine NSAID, colchicine, aspirin NSAID, famotidine NSAID, IVIg, IV methylprednisolone, PO prednisone NSAID, IVIg, IV methylprednisolone, PO prednisone, aspirin IVIg, PO prednisone  NSAID, famotidine, furosemide

Abbreviations: HHV-6, human herpesvirus-6; IgG, immunoglobulin G; IgM, immunoglobulin M; INR, international normalized ratio; IV, intravenous; LGE, late gadolinium enhancement; LFNC, low flow nasal cannula; LV, left ventricular; LVEF, left ventricular ejection fraction; PO, per os (oral); q12hr, every 12 hours; RF, regurgitant fraction; RV, right ventricular; —, not done.

Study Author Conclusions

Our case series has inherent limitations. We compiled cases through personal communications among colleagues rather than using a systematic surveillance system to identify cases. It was not possible to exclude all alternative etiologies including idiopathic and other infectious etiologies, and there was not a systematic diagnostic evaluation for other viral etiologies. Cardiac biopsy was not performed on any patients because they were all clinically stable during hospitalization. However, no patient had evidence of a preceding or concurrent symptomatic viral illness to implicate as an etiology of myocarditis, and the lack of eosinophilia dissuades a hypersensitivity reaction.

The pathophysiology of myocarditis in these patients is indeterminate, and we do not know if it is the same or different from classic myopericarditis or myopericarditis after other vaccines, associated with acute COVID-19, or with MIS-C. Given the nature of a case series, we cannot determine the incidence rate of myocarditis and myopericarditis after COVID-19 mRNA vaccination. Finally, a negative nucleocapsid antibody test result does not conclusively rule out the possibility of natural infection.

A series of U.S. cases of myocarditis and myopericarditis in adolescent male individuals occurred after the second dose of the Pfizer-BioNTech COVID-19 mRNA vaccine. Fortunately, none of our patients was critically ill and each was discharged from the hospital. At present, there is no definite causal relationship between these cases and vaccine administration. 



References:

Marshall M, Ferguson ID, Lewis P, et al. Symptomatic acute myocarditis in 7 adolescents after Pfizer-BioNTech COVID-19 vaccination. Pediatrics. 2021;148(3):e2021052478. doi:10.1542/peds.2021-052478.

 

COVID-19 Vaccine and Myocarditis 

Design

Pooled analysis of case series and case reports (till June 27, 2021)

Case Presentation

 Characteristics and outcomes of patients with myocarditis related to COVID-19 vaccine 

 

Age

Sex

Type of vaccine

Dose

 Peak cardiac troponin I (ng/mL)  Peak cardiac troponin T (ng/mL)  LVEF (%) Time to resolution (days) 
1 25 M Moderna 2nd 20.4 - 55% 3
2 21  F  Moderna  2nd  4.4  -  50% 1 
3 17  M  Pfizer-BioNTech 1st  51.37  -  53%  6 
4 28  M  J&J N/A  17.08  -  50%  2 
5 39  M  Moderna  2nd  11.01  -  56% 4 
6 39  M  Pfizer-BioNTech 2nd  13  -  52%  3 
7 24  M  Pfizer-BioNTech  1st  0.37  -  48%  2 
8 19  M  Pfizer-BioNTech  2nd  4.49  -  50%  3 
9 20  M  Pfizer-BioNTech  2nd  0.48  -  52%  4 
10 23  M  Pfizer-BioNTech  2nd  7  -  50%  2 
11 52 M Moderna 2nd  6.77  -  54%  4 
12 16 M Pfizer-BioNTech  2nd  12.56  1693 61%  6 
13 30 M Pfizer-BioNTech  2nd  18.94  -  "normal"  Resolved (duration not reported)
14 24 M Moderna 2nd  -  -  65%  Resolved (duration not reported)
15 39 M Pfizer-BioNTech 1st  - 854  "normal" 6

M =male; F =female; LVEF =left ventricular ejection fraction

Study Author Conclusions

This pooled analysis of the available data shows several important findings:

First, myocarditis related to COVID-19 vaccines mostly occurs in young male individuals following the second dose of the vaccine. Second, myocarditis related to COVID vaccines mostly occurs with mRNA vaccines (ie, Pfizer-BioNTech and Moderna COVID-19 vaccines). Third, in all the reported cases of myocarditis related to COVID-19 vaccine, clinical symptoms resolved within 6 days with preservation of the cardiac function. Third, no complications were reported in any of these patients. This analysis shows that myocarditis related to COVID-19 vaccine has an overall fast recovery with no short-term complications.



References:

Salah HM, Mehta JL. COVID-19 vaccine and myocarditis. Am J Cardiol. 2021:S0002-9149(21)00639-1. doi: 10.1016/j.amjcard.2021.07.009.

 

Association of Myocarditis with BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children

Design

Case series (N=15)

Case Presentation

 Characteristics of Patients with Myocarditis after COVID-19 Vaccine

Characteristic

 At time of admission Outpatient follow-up

Age, years

 15 (12 to 18) NA

Male

 14 (93%) NA 

Onset of symptom after vaccine, days

  3 (1 to 6) NA 

Race/ethnicity

Non-Hispanic White

Hispanic White

Other Hispanic

Other non-Hispanic

Unknown

8 (53%)

2 (15)

1 (8%)

1 (8%)

3 (20%)

 

NA

NA

NA

NA

NA 

Day at follow-up, days

 NA 6 (1 to 13)

Duration of symptoms, days

  3 (1 to 9) NA

Chest pain

Fever

Myalgia

Headache

Fatigue

15 (100%)

10 (67%)

8 (53%)

6 (40%)

6 (40%)

1 (7%)

0 (0%)

0 (0%)

0 (0%)

3 (20%)
Duration of hospitalization, days 2 (1 to 5) NA 
Immunomodulatory treatment 7 (47%) 7 (47%)

Laboratory values

Troponin level, ng/mL (normal ≤0.01)

BNP, pg/mL (normal <10)

CRP, mg/dL (normal ≤0.50)

 

0.25 (0.08 to 3.15)

22 (10 to 184)

3.01 (0.69 to 10.00)

 

0.01 (0.01 to 0.16)

12 (10 to 64)

0.24 (0.03 to 0.86)

ECG

Diffuse ST-segment elevation

T-wave inversion

 

9 (60%)

0 (0%)

 

6 (40%)

3 (30%)

Echocardiogram

Ejection fraction, %

Circumferential strain, %

Circumferential strain z score

Longitudinal strain, %

Longitudinal strain z score

Septal e', cm/s

Septal e' z score

Septal E/e' ratio

Septal E/e' ratio z score

Lateral e', cm/s

Lateral e' z score

Lateral E/e' ratio 

Lateral E/e' ratio z score

 

58.6 (43.7 to 64.7)

-23.4 (-34.2 to -15.3)

-1.8 (-4.0 to 1.1)

-19.2 (-26.8 to -11.1)

-0.9 (-3.3 to 1.8)

12.6 (11.0 to 18.2)

-0.5 (-1.3 to 2.2)

6.9 (5.0 to 8.4)

-0.1 (-1.2 to 0.9)

15.3 (11.1 to 22.7)

-1.3 (-2.7 to 1.3)

5.9 (3.0 to 7.6)

0.5 (-1.4 to 1.7) 

 

59.3 (54.4 to 71.5)

-28.8 (-35.0 to -23.2)

-0.3 (-1.9 to 1.4)

-20.7 (-24.4 to -15.1)

-0.3 (-2.0 to 1.0)

13.0 (9.4 to 18.4)

-0.4 (-2.0 to 2.2)

7.9 (4.1 to 10.1)

0.6 (-1.8 to 1.9)

16.9 (10.4 to 25.6)

-0.7 (-2.8 to 2.3)

5.7 (3.4 to 9.2)

0.4 (-1.2 to 2.6)  

Cardiac MRI

Time from onset of symptoms, days

Regional hyperintensity on T2-weighted imaging

Extracellular volume fraction, %

LV global T2, ms

LV global native T1, ms

Late gadolinium enhancement

 

3 (1 to 7)

2 (13%)

27 (22 to 37)

51.5 (47.0 to 57.6)

1048 (963 to 1121)

12 (80%)

 

NA

NA

NA

NA

NA

NA

Data are presented in median (range).

Abbreviations: BNP, brain natriuretic peptide; CRP, C-reactive protein; e', early diastolic tissue Doppler velocity; E, mitral inflow early diastolic pulsed-Doppler velocity; ECG, electrocardiogram; LV: left ventricular; MRI, magnetic resonance imaging; T2, transverse relaxation time; T1, longitudinal relaxation time.

Study Author Conclusions

In this case series of 15 children who were hospitalized with myocarditis after receipt of the BNT162b2 messenger RNA COVID-19 vaccine for 1 to 5 days, boys were most often affected after the second vaccine dose, 3 patients had ventricular systolic dysfunction, and 12 patients had late gadolinium enhancement on cardiac magnetic resonance imaging. There was no mortality, and all but 1 patient had normal echocardiogram results on follow-up 1 to 13 days after discharge.

To date (July 20, 2021- accepted for publication), there have been 1,226 reports of myocarditis after messenger RNA vaccination to the Vaccine Adverse Event Reporting System (VAERS), including 687 in persons aged less than 30 years. Crude reporting rates using vaccine administration data estimates the highest rate among male individuals aged 12 to 17 years (62.8 cases per million), similar to our observations. Despite the risks of myocarditis associated with vaccination, the benefits of vaccination likely outweigh risks in children and adolescents. It is estimated that COVID-19 vaccination in males aged 12 to 29 years can prevent 11 ,000 COVID-19 cases, 560 hospitalizations, 138 intensive care unit admissions, and 6 deaths compared with 39 to 47 expected myocarditis cases. 



References:

Dionne A, Sperotto F, Chamberlain S, et al. Association of myocarditis with BNT162b2 messenger RNA COVID-19 vaccine in a case series of children. JAMA Cardiol. 2021:e213471. doi: 10.1001/jamacardio.2021.3471.