https://orcid.org/0000-0003-1701-4970
Abstract
Variable clinical criteria taken by medical professionals across the world for myocarditis following coronavirus disease 2019 (COVID-19) vaccination along with wide variation in treatment necessitates understanding and reviewing the same. A systematic review was conducted to elucidate the clinical findings, laboratory parameters, treatment and outcomes of individuals with myocarditis after COVID-19 vaccination after registering with PROSPERO. Electronic databases including MEDLINE, EMBASE, PubMed, LitCovid, Scopus, ScienceDirect, Cochrane Library, Google Scholar and Web of Science were searched. A total of 85 articles encompassing 2184 patients were analysed. It was a predominantly male (73.4%) and young population (mean age: 25.5 ± 14.2 years) with most having taken an mRNA-based vaccine (99.4%). The mean duration from vaccination to symptom onset was 4.01 ± 6.99 days. Chest pain (90.1%), dyspnoea (25.7%) and fever (11.9%) were the most common symptoms. Only 2.3% had comorbidities. CRP was elevated in 83.3% and cardiac troponin in 97.6% patients. An abnormal ECG was reported in 979/1313 (74.6%) patients with ST-segment elevation being most common (34.9%). Echocardiographic data were available for 1243 patients (56.9%), of whom 288 (23.2%) had reduced left ventricular ejection fraction. Non-steroidal antiinflammatory drugs (76.5%), steroids (14.1%) followed by colchicine (7.3%) were used for treatment. Only 6 patients died among 1317 of whom data were available. Myocarditis following COVID-19 vaccination is often mild, seen more commonly in young healthy males and is followed by rapid recovery with conservative treatment. The emergence of this adverse event calls for harmonizing case definitions and definite treatment guidelines, which require wider research.
Introduction
Coronavirus disease 2019 (COVID-19) has spread as a pandemic causing global morbidity and mortality. Vaccination against COVID-19 infection is of prime importance during the ongoing pandemic as it can help in the prevention of disease, lower the severity and decrease the spread of COVID-19, especially following the emergence of novel COVID-19 variants of concern.1 There are multiple types of COVID-19 vaccines including inactivated virus, virtual vector-based and RNA-based vaccines. Administration of COVID-19 vaccines can lead to adverse events following vaccination (AEFI). COVID-19 vaccine-related AEFI are most often mild2 with local symptoms; however, at times, there can be severe and systemic manifestations. One such AEFI reported recently is the vaccine-induced myocarditis, which was found to occur in various countries using the mRNA-based COVID-19 vaccines. Post-vaccination myocarditis has been previously reported as an adverse event3 following smallpox and anthrax vaccines.4 With an ever-expanding global coverage with mRNA vaccines, there has been an increase in the number of reported cases of myocarditis following COVID-19 vaccination. Current estimates suggest that the overall prevalence of COVID-19 vaccine-associated myocarditis is around 3 per 100 000 patients (0.003%).5 This led to the US Food and Drug Administration adding a warning regarding the risk of myocarditis following administration of BNT162b2 and mRNA-1273 vaccines.6 This systematic review was conducted to elucidate the clinical features, laboratory findings, treatment modalities and outcomes of individuals with myocarditis following COVID-19 vaccination.
Methods
We aimed to evaluate the demographic profile, clinical signs and symptoms, laboratory findings, treatment modalities and outcomes of individuals with myocarditis following vaccination against COVID-19. Electronic databases including MEDLINE, EMBASE, PubMed, LitCovid, Scopus, ScienceDirect, Cochrane Library, Google Scholar and Web of Science were searched. Additionally, preprint repositories (BioRxiv and MedRxiv) and reference lists of the included studies were taken as additional sources. All publications in the English language from 1 December 2020 up to 10 January 2022 were reviewed. The combination of the following keywords was used as the search strategy for literature search in the various databases: ‘Age group [individuals with age restriction (12 years)] AND Vaccine (COVID-19 vaccine, novel coronavirus vaccine, SARS-CoV-2 vaccine, 2019-nCoV vaccine, severe acute respiratory syndrome coronavirus 2 vaccine, mRNA vaccine, BNT162b2 vaccine, Ad26.COV2. S vaccine, mRNA-1273 vaccine) AND Condition [Myocarditis, myopericarditis, heart inflammation]’. The search strategy had focussed on keywords involving the myocarditis (myocarditis, myopericarditis), as well as the association with COVID-19 vaccine and individuals over 12 years of age. Studies including case reports, case series, case–control and observational (prospective or retrospective) studies, brief communications and letters to the editors that incorporated incidence, clinical, laboratory, imaging as well as the hospital course of patients with myocarditis post-COVID-19 vaccination in individuals above 12 years were included. Studies with no accessible full-text versions, reporting cases with only pericarditis without myocarditis, no patient data or incomplete data and those which were not in English language were excluded. The titles and abstracts of the articles were screened based on the above inclusion criteria independently by three authors (P.I., M.G., D.M.). In case of any conflict, it was settled by the senior most author (P.I.). Following this, the entire text of all the articles was screened by two authors (S.K. and P.I.). The entire data collected include first author name, year, journal, country, study design, number of cases, study population, age, sex distribution, type of vaccine received, number of doses received, interval between symptoms and first dose, interval between symptoms and second dose, symptomatology, duration of symptoms, comorbidities, organ system involvement, laboratory investigations, cardiac imaging including echocardiography and cardiac magnetic resonance imaging findings, complications, treatment details, need for intensive care unit (ICU) admission, oxygen support, mechanical ventilation, vasoactive drugs, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), length of stay and outcome in terms of ICU stay, need for mechanical ventilation, inotropic support and mortality were recorded using Google Sheets (Google, Mountain View, CA, USA). All signs and symptoms pre and any time during the patient’s hospitalization were included. All echocardiograms were taken into consideration. Ejection fraction (EF), wall motion abnormalities, valvular dysfunction, pericardial effusion, coronary artery dilation and aneurysm were recorded. Cardiac dysfunction was defined as a left ventricular ejection fraction (LVEF) <55% and was categorized into mild (LVEF: 41–55%), moderate (LVEF: 31–40%) and severe (LVEF: <30%) left ventricular (LV) dysfunction.7 The diagnosis of vaccine-induced myocarditis was based on the Brighton Collaboration case definition8 which is enumerated in Figure 1. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was followed to guide the data extraction process. Study quality was determined based on the quality assessment tool published by the National Institutes of Health.9 Furthermore, the level of evidence was assessed according to Sackett.10 The study protocol was registered with International Prospective Register of Systematic Reviews (PROSPERO) with the following registration number CRD42021287188. Continuous data were summarized as mean ± standard deviation and categorical data summarized as counts with percent. Data analysis was performed using SPSS Statistics version 24 for Mac (IBM Corporation). Important outcomes of the review were determining the clinical presentation and outcomes of myocarditis post-vaccination against COVID-19 in individuals above 12 years for which (i) pooled estimate of demographic features, clinical details and organ system involvement, (ii) pooled estimate of laboratory investigations, treatment details and (iii) pooled estimate of outcome including length of stay, need for ICU stay, mechanical ventilation, inotropic support and mortality were calculated.
Figure 1.
Brighton Collaboration case definition for the diagnosis of vaccine-induced myocarditis.
Results
A total of 2011 potentially relevant abstracts were identified from Medline, PubMed, Embase, Scopus, Cochrane Library, WHO global COVID database and Google scholar from 1 December 2020 till 10 January 2022. Out of these, 1427 were removed as they were duplicates. Out of 584 studies left, 499 were excluded due to various reasons including articles not in English, inclusion criteria not met, only abstract, no data on myocarditis, focus on COVID-19 only, review article and scientific letter with no patient data. Ultimately, 85 articles were included in this review with a total sample size of 2184 patients who had developed myocarditis following COVID-19 vaccination (Figure 2 shows the PRISMA flow diagram). The summary of the included studies is summarized in Table 1.11–95
Figure 2.
PRISMA diagram of the systematic review.
Table 1.
Summary of the studies reporting myocarditis after SARS-CoV-2 vaccination
| Sn | First author | Number of cases/age range | Vaccine/dose | Symptoms | Laboratory investigations | ECG/echocardiography | Cardiac imaging (LGE) and biopsy | Treatment | Outcomes |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Shaw et al.11 | n = 4/16–31 years | Pfizer (3/4), Moderna (1/4)/first dose (2/4), second dose (2/4) | Chest pain (4/4) | Raised Trop I (4/4) | ST elevation (1/4)/normal Echo (4/4) | LGE (4/4), no biopsy done | Treatment not reported | Recovered and did not require hospitalization (4/4) |
| 2 | Schauer et al.12 | n = 13/12–17 years | Pfizer (13/13), second (13/13) | Dyspnoea (5/13), fever (5/13), headache (5/13), arthralgia (6/13), nausea (1/13), vomiting (1/13), myalgia (7/13) | Raised CRP (3/13), raised Trop T (13/13) | ST elevation (8/13), nonspecific ST (1/13)/reduced EF (2/13) | LGE (4/4), no biopsy done | IVIg (3/13), symptomatic therapy (13/13) | Hospitalized and discharged (13/13) |
| 3 | Azir et al.13 | n = 1/17 years | Pfizer/second | Dyspnoea, chest pain | Raised Trop T | ST elevation/normal ECHO | LGE +, no biopsy done | Antiplatelet | Hospitalized and discharged |
| 4 | Wilson et al.14 | n = 1/16 years | Pfizer/second | Chest pain | Raised Trop T, raised BNP | Nonspecific ST-T changes/normal ECHO | LGE +, no biopsy done | NSAIDs | Recovered and did not require hospitalization |
| 5 | Mansour et al.15 | n = 2/21–25 years | Moderna/second | Fever (1/2), dyspnoea (1/2), chest pain (2/2), myalgia (1/2), headache (1/2) | Raised CRP (2/2), raised D-dimer (1/2), raised Trop I (2/2) | ST elevation (2/2)/reduced EF (1/2) | LGE + (2/2), no biopsy done | Managed conservatively | Recovered and did not require hospitalization (2/2) |
| 6 | Miqdad et al.16 | n = 1/18 years | Pfizer/second | Chest pain | Raised CRP, raised Trop I | ST elevation/normal ECHO | Myocardial oedema +, LGE +, no biopsy done | NSAIDs, colchicine, antiplatelet, ACEi/ARB | Hospitalized and discharged |
| 7 | Gautam et al.17 | n = 1/66 years | Pfizer/second | Palpitation, chest pain, nausea, vomiting, myalgia | Raised ESR, raised Trop I | Nonspecific ST-T changes, ECHO not done | LGE +, no biopsy done | Managed conservatively | Hospitalized and discharged |
| 8 | Das et al.18 | n = 25/12–17 years | Pfizer (25/25)/first dose (3/25), second dose (22/25) | Dyspnoea (3/25), fever (7/25), syncope (1/25), chest pain (25/25), nausea (2/25), vomiting (2/25), myalgia (3/25), headache (2/25), chills (1/25), sweating (1/25), shoulder and neck pain (1/25) | Raised CRP (10/17), raised Trop T (25/25) | ST elevation (14/25), T wave inversion (3/25), nonspecific ST-T changes (3/25), NSVT (3/25), VPC (1/25), ST depression (1/25), PR depression (1/25), first degree AV block with LBBB (1/25)/reduced EF (2/25) | Myocardial oedema (4/16), LGE + (16/16), no biopsy done | NSAIDs (23/24), Steroids (1/24), antiplatelet (1/24), diuretics (3/24), ACEi/ARB (2/24), IVIg (2/24) | Hospitalized and discharged (22/25), Recovered and did not require hospitalization (3/25) |
| 9 | Koizumi et al.19 | n = 2/22–27 years | Moderna/second | Chest pain (2/2) | Raised Trop T (2/2), raised CPK-MB (1/2) | ST elevation (2/2)/normal ECHO (2/2) | LGE (1/1), Biopsy—no specific findings (1/2), no inflammatory cell infiltrates (1/2) | NSAIDs (2/2) | Hospitalized and discharged (1/2), Recovered and did not require hospitalization (1/2) |
| 10 | Ujueta et al.20 | n = 1/62 years | Janssen/first | Myalgia | Positive procalcitonin, raised CRP, raised Trop I, raised Pro-BNP, raised AST, raised ALT | Sinus tachycardia, T inversion/reduced EF, RV dysfunction, pericardial effusion | MRI not reported, biopsy—lymphohistiocytic myocarditis with sparse eosinophils | Steroids, oxygen, ventilation, inotropes | Hospitalized and died |
| 11 | Nevet et al.21 | n = 3/20–29 years | Pfizer/second (3/3) | Fever (3/3), chest pain (3/3) | Raised CRP (1/1), raised Trop T/I (3/3) | ST elevation (3/3)/normal ECHO (3/3) | Myocardial oedema (3/3), LGE + (3/3), no biopsy done | NSAIDs (3/3), colchicine (3/3) | Hospitalized and discharged (3/3) |
| 12 | Cereda et al.22 | n = 1/21 years | Pfizer/second | Fever, chest pain | Raised Trop I | ST elevation, NSVT/LV hypokinesia | Myocardial oedema, LGE +, no biopsy done | Beta-blockers, ACEi/ARB, antibiotics | Hospitalized and discharged |
| 13 | Nguyen et al23 | n = 1/20 years | Moderna/first | Fever, chest pain, myalgia, chills | Thrombocytopenia, raised Trop T, raised Pro-BNP | Pre-excitation/reduced EF | Myocardial oedema, LGE +, biopsy—myocardial oedema and profound mononuclear infiltration | Not reported | Hospitalized and discharged |
| 14 | Watkins et al.24 | n = 1/20 years | Pfizer/second | Chest pain | Raised Trop T | ST elevation, PR depression/small pericardial effusion | MRI done—Myocardial oedema and LGE not reported, no biopsy done | NSAIDs, colchicine, beta-blocker | Hospitalized and discharged |
| 15 | Choi et al.25 | n = 1/22 years | Pfizer/first | Chest pain | Not reported | Ventricular fibrillation/ECHO not reported | MRI not reported, biopsy—diffuse inflammatory infiltration with neutrophils and histiocyte predominance | Not reported | Hospitalized and died |
| 16 | Rosner et al.26 | n = 7/19–39 years | Janssen (1/7), Pfizer (5/7), Moderna (1/7)/first dose (2/7), second dose (5/7) | Dyspnoea (2/7), fever (2/7), chest pain (7/7), myalgia (1/7), headache (1/7), chills (1/7), numbness and tingling (1/7) | Raised ESR (1/6), raised CRP (5/7), raised Trop I (7/7) | Sinus tachycardia (2/7), ST elevation (3/7), T inversion (1/7), nonspecific ST-T changes (1/7), PR depression (1/7)/reduced EF (4/7) | LGE + (7/7), no biopsy done | NSIADs (3/7), colchicine (3/7), steroids (1/7), beta-blockers (3/7), ACEi/ARB (2/7) | Hospitalized and discharged (7/7) |
| 17 | Chelala et al.27 | n = 5/16–19 years | Pfizer (4/5), Moderna (1/5)/second dose (5/5) | Chest pain (5/5) | Raised CRP (2/5), raised Trop I (5/5), raised BNP (1/1) | Sinus bradycardia (1/5), ST elevation (1/5)/reduced EF (1/5), LAD and RCA ectasia (1/5) | Myocardial oedema (4/5), LGE + (5/5), no biopsy done | NSIADs (1/5), colchicine (1/5), antiplatelet (1/5), beta-blocker (3/5) | Hospitalized and discharged (5/5) |
| 18 | Verma et al.28 | n = 2/42–45 years | Pfizer (1/2), Moderna (1/2)/ first dose (1/2), second dose (1/2) | Dyspnoea (2/2), fever (1/2), chest pain (1/2), dizziness (1/2) | Raised Trop I (2/2), raised Pro-BNP (1/1), raised AST (2/2), raised ALT (1/2), | Sinus tachycardia (1/2), ST elevation (1/2), ST depression (1/2)/reduced EF (2/2), pericardial effusion (2/2) | LGE + (1/1), Biopsy—inflammatory infiltrates (2/2) | NSAIDs (1/2), parenteral anticoagulant (2/2), steroids (2/2), antiplatelet (1/2), diuretics (2/2), beta-blockers (1/2), ACEi/ARB (1/2), antibiotics (2/2), oxygen (1/2), ventilation (1/2), inotropes (2/2) | Hospitalized and discharged (1/2), Hospitalized and died (1/2) |
| 19 | Fleming-Nouri et al.29 | n = 8/16–24 years | Pfizer (8/8)/second dose (8/8) | Chest pain (8/8) | Raised Trop T (1/1), raise Trop I (7/7) | ST elevation (7/8)/Mild LV hypokinesia (1/8) | LGE+ (3/5), no biopsy done | NSAIDs (5/5), steroids (4/5), antiplatelets (3/5), IVIg (4/5) | Hospitalized and discharged (8/8) |
| 20 | Shumkova et al.30 | n = 1/23 years | Pfizer/second | Dyspnoea, fever, chest pain | Raised CRP, raised CPK-MB, raised Trop T, raised Pro-BNP | Sinus tachycardia, ST elevation/reduced EF | LGE+, no biopsy done | NSAIDs, steroids, antibiotic | Hospitalized and discharged |
| 21 | Vollman et al.31 | n = 1/28 years | Pfizer/first | Fever, chest pain, myalgia | Raised CRP, raised Trop T | ST elevation/ECHO not done | LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 22 | Cimaglia et al.32 | n = 1/24 years | Pfizer/first | Chest pain | Raised CPK-MB, raised Trop T | Sinus tachycardia, ST elevation/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 23 | Patrignani et al.33 | n = 1/56 years | Pfizer/first | Abdominal pain, sweating | Raised Trop T | Normal ECG/normal ECHO | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 24 | Habib et al.34 | n = 1/37 years | Pfizer/second | Fever, chest pain, myalgia, joint pain, headache, chills | Raised Trop T | ST elevation/normal ECHO | LGE+, no biopsy done | Parenteral anticoagulant, antiplatelet, beta-blocker | Hospitalized and discharged |
| 25 | Schmitt et al.35 | n = 1/19 years | Pfizer/second | Chest pain, myalgia, headache | Raised CRP, raised Trop T | Sinus tachycardia, ST elevation/normal ECHO | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 26 | Alania-Torres et al.36 | n = 1/28 years | Pfizer/second | Dyspnoea, fever, chest pain, diarrhoea, myalgia, headache | Raised Trop I | Normal ECG/reduced EF | MRI not reported, no biopsy done | Colchicine, antiplatelet, diuretic, beta-blocker, ARNI | Hospitalized and discharged |
| 27 | Kim et al.37 | n = 1/24 years | Pfizer/second | Chest pain, myalgia | Raised CRP, raised Trop I | ST elevation/pericardial effusion | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 28 | Matta et al.38 | n = 1/27 years | Pfizer/second | Chest pain, myalgia | Thrombocytopenia, raised CRP, raised Trop I | Normal ECG/normal ECHO | MRI not reported, no biopsy done | NSAIDs | Hospitalized and discharged |
| 29 | Tiwari et al.39 | n = 1/33 years | Covaxin/first | Dyspnoea, oedema | Raised CPK-MB, raised AST, raised ALT | Sinus tachycardia/normal ECHO | Myocardial oedema +, no biopsy done | Steroid, beta-blocker | Recovered and did not require hospitalization |
| 30 | Mouch et al.40 | n = 6/16–45 years | Pfizer/first dose (1/6), second dose (5/6) | Chest pain (6/6) | Thrombocytopenia (1/6), raised CRP (5/6), raised Trop T (6/6), raised AST (4/6), raised ALT (1/6) | Sinus tachycardia (1/6), ST elevation (6/6), T inversion (3/6), PR depression (1/6)/reduced EF (2/6), minimal MR (1/6), minimal TR (1/6) | Myocardial oedema (4/6), LGE+ (6/6), no biopsy done | NSAIDs (6/6), colchicine (6/6) | Hospitalized and discharged (6/6) |
| 31 | Tailor et al.41 | n = 1/44 years | Moderna/second | Dyspnoea, chest pain | Raised CRP, raised Trop T, raised Pro-BNP | ST elevation/reduced EF | LGE+, no biopsy done | Colchicine, diuretics, beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 32 | Dickey et al.42 | n = 6/17–37 years | Pfizer (5/6), Modrna (1/6)/second dose (6/6) | Fever (3/6), chest pain (6/6), myalgia (4/6), headache (1/6), chills (1/6), rhinorrhoea (1/6) | Raised Trop T (6/6) | ST elevation (5/6), nonspecific ST-T changes (1/6), NSVT (1/6), PR depression (2/6)/reduced EF (5/6) | LGE+ (6/6), no biopsy done | Not reported | Hospitalized and discharged (6/6) |
| 33 | Sokolska et al.43 | n = 1/21 years | Pfizer/first | Chest pain | Raised CRP, raised Trop T, raised Pro-BNP | ST elevation, T inversion/normal ECHO | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 34 | Nassar et al.44 | n = 1/70 years | Janssen/first | Dyspnoea | Positive procalcitonin, raised CRP, raised Trop I | Sinus tachycardia, T inversion/reduced EF | MRI not reported, no biopsy done | Antibiotics, oxygen, ventilation, inotropes | Hospitalized and died |
| 35 | Montgomery et al.45 | n = 23/20–51 years | Pfizer (7/23), Moderna (16/23)/first dose (3/23), second dose (20/23) | Chest pain (23/23) | Raised Trop (23/23) | ST elevation (19/23), T inversion (19/23), nonspecific ST-T changes (19/23)/reduced EF (4/23) | Myocardial oedema (8/8), LGE+ (8/8), no biopsy done | Not reported | Hospitalized and discharged (23/23) |
| 36 | Minocha et al.46 | n = 1/17 years | Pfizer/second dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation/reduced EF | LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 37 | Starekova et al.47 | n = 5/17–38 years | Pfizer (3/5), Moderna (2/5)/ second dose (5/5) | Dyspnoea (2/5), fever (3/5), chest pain (5/5), nausea (2/5), myalgia (4/5), headache (2/5) | Raised Trop I (5/5) | ST elevation (2/5), T inversion (3/5)/reduced EF (3/5) | Myocardial oedema (5/5), LGE+ (5/5), no biopsy done | Not reported | Hospitalized and discharged (5/5) |
| 38 | Kim et al.48 | n = 4/23–70 years | Pfizer (2/4), Moderna (2/4),/ second dose (4/4) | Dyspnoea (3/4), fever (3/4), palpitations (1/4), syncope (1/4), chest pain (1/4), myalgia (3/4), headache (1/4), diaphoresis (1/4) | Raised ESR (1/3), raised CRP (2/3), raised Trop T (2/2), raised Trop I (2/2), raised Pro-BNP (2/3) | ST elevation (4/4), PR depression (2/4)/reduced EF (2/4) | LGE+ (4/4), no biopsy done | NSAIDs (2/4), colchicine (3/4), steroids (1/4) | Hospitalized and discharged (4/4) |
| 39 | Witberg et al.49 | n = 54/21–40 years | Pfizer (54/54)/second dose (54/54) | Fever (5/54), dyspnoea (3/54), palpitations (1/54), chest pain (44/54), myalgia (1/54) | Raised CRP (18/28), raised Trop T (41/41) | ST elevation (18/38), sinus tachycardia (1/38), T inversion (7/38), nonspecific ST-T changes (2/38), AF (1/38), NSVT (2/38)/reduced EF (14/48), pericardial effusion (10/48) | LGE+ (9/11), Biopsy—lymphocyte and eosinophil infiltration (1/1) | NSAIDs (12/54), colchicine (17/54), oral NOAC (1/54), steroid (1/54), antiplatelet (2/54), beta-blockers (20/54), ACEi/ARB (16/54), ECMO (1/54), inotropes (1/54), |
|
| 40 | Muthukumar et al.50 | n = 1/52 years | Moderna/second dose | Chest pain | Raised ESR, raised CRP, raised D-dimer, raised Trop T, raised AST, raised ALT | RBBB/normal ECHO | LGE+, no biopsy done | Beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 41 | Istampoulouoglou et al.51 | n = 14/17–88 years | Pfizer (4/14), Moderna (10/14)/first dose (5/14), second dose (9/14) | Dyspnoea (2/14), fever (2/14), palpitation (2/14), syncope (1/14), chest pain (9/14), abdominal pain (1/14), myalgia (1/14) | Raised Trop I (1/1), raised Trop T (11/12) | NSVT and SVT (1/10)/reduced EF (5/13) | Myocardial oedema (9/13), LGE+ (9/14), no biopsy done | NSAIDs (4/14), colchicine (2/14), diuretics (2/14), beta-blockers (6/14), ACEi/ARB (7/14), SGLT-2i (1/14), antibiotic (3/14) | Hospitalized and discharged (14/14) |
| 42 | Abbate et al.52 | n = 2/27–34 years | Pfizer (2/2)/first dose (1/2), second dose (1/2) | Fever (1/2), cough (1/2), chest pain (1/2), nausea (2/2), vomiting (2/2) | Raised CRP (2/2), raised D-dimer (1/2) | Sinus tachycardia (2/2), ST elevation (1/2), nonspecific ST-T changes (1/2)/reduced EF (2/2) | Myocardial oedema (1/1), LGE+ (1/1), no biopsy done | Steroids (2/2), IVIg (2/2), Anakinra (2/2), ECMO (2/2) | Hospitalized and discharged (1/2), hospitalized and died (1/2) |
| 43 | Viskin et al.53 | n = 8/20–34 years | Moderna (8/8)/second dose (8/8) | Chest pain (8/8), myalgia (8/8) | Raised Trop T (8/8) | ST elevation (5/8)/reduced EF (3/8) | LGE+ (6/8), no biopsy done | Not reported | Hospitalized and discharged (8/8) |
| 44 | Vidula et al.54 | n = 2/18–19 years | Pfizer (1/2), Moderna (1/2)/second dose (2/2) | Dyspnoea (1/2), fever (1/2), chest pain (2/2), myalgia (1/2) | Raised CRP (2/2), raised Trop T (2/2) | ST elevation (2/2), sinus tachycardia (1/2)/reduced EF (2/2) | Myocardial oedema (2/2), LGE+ (2/2), no biopsy done | NSAIDs (1/2), colchicine (1/2), beta-blockers (2/2), ACEi/ARB (1/2) | Hospitalized and discharged (2/2) |
| 45 | Chamling et al.55 | n = 3/20–68 years | Pfizer (2/3), Astra-Zeneca (1/3)/first dose (2/3), second dose (1/3) | Fever (1/3), chest pain (3/3), headache (1/3) | Raised CRP (1/3), raised Trop T (3/3) | ST elevation (2/3)/normal ECHO (3/3) | LGE+ (3/3), no biopsy done | Parenteral anticoagulant (1/3), antiplatelet (2/3), beta-blocker (1/3), ACEi/ARB (1/3) | Hospitalized (3/3). Outcome not reported |
| 46 | Albert et al.56 | n = 1/24 years | Moderna/second dose | Fever, chest pain, myalgia, chills | Raised Trop I | Normal ECG/normal ECHO | Myocardial oedema +, LGE +, no biopsy done | Beta-blocker | Hospitalized and discharged |
| 47 | Onderko et al.57 | n = 3/25–36 years | Pfizer (2/3), Moderna (1/3)/second dose (3/3) | Chest pain (3/3), myalgia (2/3), chills (1/3) | Raised CRP (2/2), raised Trop T (3/3) | ST elevation (2/3)/normal ECHO | Myocardial oedema (3/3), LGE+ (3/3), no biopsy done | NSAIDs (1/3), colchicine (1/3), beta-blockers (3/3) | Hospitalized and discharged (3/3) |
| 48 | Jain et al.58 | n = 63/12–20 years | Pfizer (59/63), Moderna (4/63)/first dose (1/63), second dose (62/63) | Dyspnoea (22/63), fever (28/63), chest pain (63/63), nausea (15/63), myalgia (24/63), headache (16/63) | Raised CRP (62/63), raised Trop T (63/63) | ST elevation (44/63), T inversion (44/63), NSVT (3/63), CHB (1/63)/reduced EF (9/63) | Myocardial odema (50/56), LGE+ (49/56), no biopsy done | NSAIDs (54/63), colchicine (4/63), steroid (15/63), antiplatelet (6/63), beta-blocker (6/63), IVIg (17/63) | Hospitalized and discharged (63/63) |
| 49 | Patel et al.59 | n = 5/19–37 years | Pfizer (4/5), Moderna (1/5)/first dose (1/5), second dose (4/5) | Dyspnoea (4/5), fever (1/5), chest pain (5/5), nausea (3/5), vomiting (1/5), myalgia (3/5), headache (3/5), chills (1/5), diaphoresis (1/5) | Raised ESR (1/4), raised CRP (3/3), raised Trop T (5/5) | Sinus tachycardia (1/5), ST elevation (1/5), PR depression (3/5), ST depression (1/5)/reduced EF (1/5) | Myocardial oedema (3/5), LGE+ (5/5), no biopsy done | NSAIDs (2/5), colchicine (4/5), antiplatelet (1/5), beta-blocker (1/5), ACEi/ARB (1/5) | Hospitalized and discharged (5/5) |
| 50 | Tano et al.60 | n = 8/15–18 years | Pfizer (8/8)/first dose (1/8), second dose (7/8) | Fever (1/8), palpitations (1/8), cough (1/8), chest pain (8/8), abdominal pain (1/8), diarrhoea (1/8), myalgia (2/8), headache (1/8) | Raised D-dimer (2/6), raised CPK-MB (3/5), raised Trop T (8/8) | ST elevation (4/8), PR depression (2/8), ST depression (2/8)/normal ECHO (8/8) | Myocardial oedema (3/3), LGE+ (3/3), no biopsy done | NSAIDs (5/8), IvIg (1/8) | Hospitalized and discharged (8/8) |
| 51 | Deb et al.61 | n = 1/67 years | Moderna/second dose | Dyspnoea, fever, PND, nausea, myalgia, chills | Raised ESR, raised CRP, raised Trop T, raised BNP | Sinus tachycardia, nonspecific ST-T changes/reduced EF | MRI not reported, no biopsy done | Diuretics, oxygen, HFNC/NIMV | Hospitalized and discharged |
| 52 | Marshall et al.62 | n = 7/14–19 years | Pfizer (7/7)/second dose (7/7) | Dyspnoea (3/7), fever (2/7), palpitation (1/7), chest pain (5/7), nausea (3/7), vomiting (2/7), myalgia (5/7), headache (1/7), chills (1/7), anorexia (1/7), paresthesia (1/7) | Raised ESR (3/7), raised CRP (4/7), raised Trop T (4/4), Trop I (3/3), raised Pro-BNP (3/4), raised AST (6/7), raised ALT (1/7) | Sinus bradycardia (1/7), ST elevation (6/7), T wave abnormalities (2/7), AV dissociation with junctional escape rhythm (1/7)/RV dysfunction (1/7), normal ECHO (7/7) | Myocardial oedema (6/7), LGE+ (6/7), no biopsy done | NSAIDs (6/7), Colchicine (1/7), steroids (4/7), antiplatelet (2/7), diuretics (1/7), IVIg (4/7), oxygen (1/7), HFNC/NIV (1/7) | Hospitalized and discharged (7/7) |
| 53 | Ambati et al.63 | n = 2/16–17 years | Pfizer (2/2)/second dose (2/2) | Dyspnoea (1 2), fever (1/2), chest pain (2/2), nausea (1/2), vomiting (1/2), myalgia (1/2), headache (1/2) | Raised ESR (1/2), raised CRP (1/2), raised D-dimer (1/2) Trop I (2/2) | ST elevation (2/2)/ECHO—not reported | MRI not reported, no biopsy done | NSAIDs (2/2) | Hospitalized and discharged (2/2) |
| 54 | Sulemankhil et al.64 | n = 1/33 years | Janssen/ first dose | Chest pain, myalgia, chills | Raised CRP, raised Trop T | ST elevation/reduced EF | LGE+, no biopsy done | Managed conservatively | Hospitalized and discharged |
| 55 | Simone et al.65 | n = 15/18–40 years | Pfizer (8/15) Moderna (7/15)/ first dose (2/15), second dose (13/15) | Chest pain (15/15) | Raised Trop I (15/15) | ST tachycardia (1/15), ST elevation (10/15), T inversion (1/15)/reduced EF (5/15) | MRI not reported, no biopsy done | Managed conservatively (15/15) | Hospitalized and discharged (15/15) |
| 56 | Ehrlich et al.66 | n = 1/40 years | Pfizer/first dose | Dyspnoea, fever, chest pain, headache | Raised CRP, raised Trop T, raised CPK-MB | ST elevation, ST depression/reduced EF | LGE+, biopsy—acute lymphocytic myocarditis | Parenteral anticoagulant, antiplatelet, beta-blocker, ACEi/ARB, ARNI | Hospitalized and discharged |
| 57 | Kaul et al.67 | n = 2/21–28 years | Pfizer (1/2), Moderna (1/2)/second dose (2/2) | Fever (2/2), chest pain (2/2), myalgia (1/2), headache (2/2), chills (1/2) | Raised CRP (2/2), raised D-dimer (1/2), Trop I (2/2) | ST elevation (2/2)/reduced EF (1/2) | LGE+ (2/2), no biopsy done | Colchicine (1/2), ACEi/ARB (1/2). ARNI (1/2) | Hospitalized and discharged (2/2) |
| 58 | Snapiri et al.68 | n = 7/16–18 years | Pfizer (7/7)/first dose (6/7), second dose (1/7) | Dyspnoea (2/7), fever (1/7), cough (1/7), chest pain (7/7), nausea (1/7), diarrhoea (1/7), headache (1/7) | Raised CRP (6/7), raised Trop T (7/7), raised Pro-BNP (3/4) | ST elevation (6/7), RBBB (1/7), ST depression (1/7), PR depression (1/7)/reduced EF (1/3), pericardial effusion (2/7) | MRI—not reported, no biopsy done | NSAIDs (5/7), antiplatelet (1/7), | Hospitalized and discharged (7/7) |
| 59 | Issak et al.69 | n = 1/15 years | Pfizer/second dose | Fever, myalgia, | Raised CRP, raised Trop T/I | ST elevation/normal ECHO | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 60 | Park et al.70 | n = 2/15–16 years | Pfizer (2/2)/first dose (1/2), second dose (1/2) | Fever (1/2), chest pain (2/2), headache (1/2) | Raised ESR (1/2), positive procalcitonin (1/2), raised Trop T (2/2), raised CPK-MB (2/2), raised Pro-BNP (2/2) | ST elevation (2/2), T-wave inversion (1/2)/reduced EF (1/2) | LGE+ (1/2), no biopsy done | Managed conservatively (2/2) | Hospitalized and discharged (2/2) |
| 61 | Diaz et al.71 | n = 20/median- 36 (26.3–48.3) years | Pfizer (9/20), Moderna (11/20)/first dose (4/20), second dose (16/20) | Chest pain (20/20) | Raised Trop T/I (19/20), raised AST (6/20), raised ALT (1/20) | ST elevation (9/20), PR depression (1/20), BBB (1/20)/reduced EF (5/20) | MRI—not reported, no biopsy done | NSAIDs (15/20), colchicine (9/20), diuretics (8/20), beta-blockers (8/20), ACEi/ARB (8/20) | Hospitalized and discharged (20/20) |
| 62 | Singh et al.72 | n = 1/24 years | Pfizer/second dose | Fever, chest pain, myalgia, headache, chills | Raised Trop I | ST depression/normal ECHO | LGE+, no biopsy done | Treatment not reported | Hospitalized and discharged |
| 63 | Chai et al.73 | n = 1/17 years | Pfizer/second dose | Dyspnoea, fever, chest pain, vomiting, diarrhoea, myalgia, headache, rash | Thrombocytopenia, positive procalcitonin, raised CRP, raised Trop T and Trop I, raised D-dimer, raised CPK-MB, | ECG—normal/reduced EF | LGE+, no biopsy done | Antibiotics, IVIg, oxygen, HFNC/NIV, inotropes | Hospitalized and discharged |
| 64 | Larson et al.74 | n = 8/21–40 years | Pfizer (5/8), Moderna (3/8) first dose (1/8), second dose (7/8) | Dyspnoea (1/8), fever (5/8), cough (1/8), chest pain (8/8), myalgia (2/8), chills (2/8) | Raised CRP (7/8), raised Trop T (8/8), raised Pro-BNP | ST elevation (6/8), aVR depression (2/8), ST depression (1/8), peaked T waves (1/8)/reduced EF (6/8) | Myocardial oedema (6/8), LGE+ (8/8), biopsy (1/1)—normal | NSAIDs (3/8), colchicine (2/8), steroids (2/8) | Hospitalized and discharged (8/8) |
| 65 | Williams et al.75 | n = 1/34 years | Moderna/second dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine, beta-blockers, ACEi/ARB | Hospitalized and discharged |
| 66 | McLean and Johnson76 | n = 1/16 years | Pfizer/second dose | Fever, chest pain, myalgia | Raised CRP, raised Trop T, raised CPK-MB, raised BNP | ST elevation/ECHO—not reported | Myocardial oedema, no biopsy done | NSAIDs, IVIg | Hospitalized and discharged |
| 67 | King et al.77 | n = 4/20–30 years | Pfizer (1/4), Moderna (3/4)/second dose (4/4) | Chest pain (4/4) | Raised CRP (3/4), raised Trop T (4/4) | ST elevation (3/4), T wave inversion (1/4), PR depression (3/4)/reduced EF (1/4) | LGE+ (1/1), no biopsy done | Treatment not reported | Hospitalized and discharged |
| 68 | Singh et al.78 | n = 2/52–65 years | ChAdOx1 (2/2)/first dose (1/2), second dose (1/2) | Dyspnoea (2/2), fever (1/2), cough (1/2), chest pain (1/2) | Raised CRP (2/2), raised Trop I (2/2), raised BNP (1/2), raised ALT (2/2) | Sinus tachycardia (1/2), ST depression (2/2)/pericardial effusion (1/2), reduced EF (2/2) | MRI—not reported, no biopsy done | Antiplatelet (2/2), diuretics (1/2), beta-blocker (1/2), ACEi/ARB (1/2), statin (1/2), nitrate (1/2), amlodipine (1/2) | Hospitalized and discharged (2/2) |
| 69 | Kim et al.79 | n = 1/29 years | Pfizer/second dose | Chest pain | Raised Trop I | ECG—normal/pericardial effusion, normal ECHO | MRI—not reported, no biopsy done | NSAIDs, steroids | Recovered and did not require hospitalization |
| 70 | D’Angelo et al.80 | n = 1/30 years | Pfizer/second dose | Dyspnoea, chest pain, nausea, sweating | Raised CRP, raised Trop T, raised CPK-MB | ST elevation, nonspecific ST-T changes/pericardial effusion, normal ECHO | LGE+, no biopsy done | NSAIDs, steroids, beta-blockers | Hospitalized and discharged |
| 71 | Sivakumaran et al.81 | n = 1/20 years | Pfizer/ second | Palpitation, chest pain | Raised Trop T, raised Pro-BNP | ST elevation/reduced EF | Myocardial oedema, LGE+, no biopsy done | Colchicine | Hospitalized and discharged |
| 72 | Pareek et al.82 | n = 11/16–53 years | Pfizer (9/11), Moderna (1/11), Ad26.COV2.S (1/11)/ first dose (1/11), second dose (10/11) | Dyspnoea (2/11), fever (7/11), palpitation (2/11), chest pain (10/11), nausea (2/11), abdominal pain (1/11), myalgia (8/11), headache (4/11), chills (2/11) | Raised CRP (6/11), raised Trop T (9/9), raised Trop I (2/2), raised Pro-BNP (3/7) | Sinus tachycardia (2/11), ST elevation (8/11), T inversion (1/11), PR depression (2/11), ST depression (1/11)/reduced EF (1/2), normal ECHO (1/2) | Myocardial oedema (4/9), LGE+ (8/9), no biopsy done | NSAIDs (11/11), colchicine (4/11), steroids (4/11), beta-blockers (3/11), ACEi/ARB (2/11), IVIg (4/11) | Hospitalized and discharged (11/11) |
| 73 | Walters et al.83 | n = 1/29 years | Pfizer/second dose | Chest pain, nausea | Raised Trop T | Sinus bradycardia, ST elevation/normal ECHO | MRI—not reported, no biopsy done | NSAIDs, colchicine, antiplatelet | Hospitalized and discharged |
| 74 | Hasnie et al.84 | n = 1/22 years | Moderna/first dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | LGE+, no biopsy done | NSAIDs, colchicine, antiplatelet, beta-blocker | Hospitalized and discharged |
| 75 | Khogali and Abdelrahman85 | n = 1/29 years | Moderna/second dose | Fever, nausea, vomiting, diarrhoea, myalgia | Raised D-dimer, raised Trop T, raised Pro-BNP | ST elevation, nonspecific ST-T waves, short PR interval/pericardial effusion, reduced EF | MRI—not done, no biopsy done | NSAIDs, colchicine, steroid, antiplatelet, inotrope | Hospitalized and discharged |
| 76 | Di Tano et al.86 | n = 1/29 years | Moderna/first dose | Fever, chest pain | Raised CRP, raised Trop T | ST elevation/ECHO—not reported | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine | Hospitalized and discharged |
| 77 | Maki et al.87 | n = 1/20 years | Moderna/second dose | Dyspnoea, fever, chest pain | Raised Trop I | Sinus tachycardia, ST elevation/pericardial effusion, reduced EF | LGE+, Biopsy—lymphocytic infiltration in myocardium | Diuretics, beta-blockers, inotrope, ACEi/ARB | Hospitalized and discharged |
| 78 | Ammirati et al.88 | n = 1/56 years | Pfizer/second dose | Chest pain | Raised D-dimer, raised CPK-MB, raised Trop T | ST elevation, peak T waves/ECHO—not reported | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine | Hospitalized and discharged |
| 79 | Rodriguez et al.89 | n = 1/68 years | AstraZeneca/first dose | Chest pain, sweating | Thrombocytopenia, raised CRP, raised Trop T | Atrial fibrillation/reduced EF | MRI—not reported, no biopsy done | Parenteral anticoagulant, inotrope | Hospitalized and discharged |
| 80 | Chen et al.90 | n = 1/16 years | Pfizer/first dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs, beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 81 | Hudson et al.91 | n = 2/22–24 years | Pfizer (2/2)/second dose (2/2) | Fever (2/2), chest pain (1/2), nausea (1/2), vomiting (1/2), myalgia (1/2), chills (2/2), substernal pain (1/2), diaphoresis (1/2) | Raised CRP (2/2), raised D-dimer (1/2), raised Trop T (2/2) | J point elevation (1/2), wide QRS complexes (1/2)/reduced EF (1/2) | MRI—nor reported, no biopsy done | NSAIDs (2/2), colchicine (2/2), antiplatelet (2/2) | Hospitalized and discharged (2/2) |
| 82 | Visclosky et al.92 | n = 1/15 years | Pfizer/second dose | Fever, chest pain, headache | Raised Trop T | ST elevation/reduced EF | MRI—not reported, no biopsy done | NSAIDs | Hospitalized and discharged |
| 83 | Dionne et al.93 | n = 15/29 years | Pfizer/first dose (1/15), second dose (14/15) | Fever (10/15), chest pain (15/15), palpitation (1/15), nausea (1/15), vomiting (1/15), myalgia (9/15), headache (6/15) | Raised CRP (8/14), raised Trop T (15/15) | ST elevation (9/15), T inversion (2/15), nonspecific ST-T changes (2/15), NSVT (1/15), PAC (1/15)/reduced EF (3/15) | Myocardial oedema (2/15), LGE+ (12/15), no biopsy done | Steroids (7/7), IVIg (7/7) | Hospitalized and discharged (15/15) |
| 84 | Oster et al.94 | n = 1626/21 years | Pfizer (490/1626) Moderna (1136/1626) first dose (273/1626); second dose (1265/1626); dose NA:(88/1626) | Dyspnoea (242/1626), palpitation (65/1626), chest pain (727/1626) | Raised Trop T/I (792/809) | ECG (569/794) Normal echo (598/721) LVEF normal (637/721) | Cardiac MRI (223/312), LGE: 223; oedema: 223, no biopsy done | Rx Received by 676/1626, NSAIDS (589/676), intravenous anticoagulant (54/676), steroids (81/676), diuretics (11/676), IVIg (78/676), antiarrhythmics (18/676), O2 (12/676), inotrope (12/676) | Hospitalized (784/813) |
| 85 | Truong et al.95 | n = 139/15.8 years | Pfizer: (131/139); Moderna: (5/139); J&J: (1/139); NR: (2/139); Dose 1: (12/139) Dose 2: (128/139) | Dyspnoea (38/139), fever (43/139), palpitation (7/139), chest pain (138/139), vomiting (17/139), diarrhoea (3/139), myalgia/fatigue (26/139), joint pain (22/139), rash (5/139) | Raised Trop T/I (139/139), raised BNP (101/139), raised NT pro BNP (8/139) |
|
| Rx by 139, NSAIDS (113/139), Colchicine (11/139), steroids (30/139), IVIg (30/139), Biologics given to 1 (Anakinra), 2 patients got inotropes. | Hospitalized and discharged (139/139). Hospital stay 2 days average and 26 were admitted to the ICU. Myocarditis was definite in 49 and probable in 91 |
| Sn | First author | Number of cases/age range | Vaccine/dose | Symptoms | Laboratory investigations | ECG/echocardiography | Cardiac imaging (LGE) and biopsy | Treatment | Outcomes |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Shaw et al.11 | n = 4/16–31 years | Pfizer (3/4), Moderna (1/4)/first dose (2/4), second dose (2/4) | Chest pain (4/4) | Raised Trop I (4/4) | ST elevation (1/4)/normal Echo (4/4) | LGE (4/4), no biopsy done | Treatment not reported | Recovered and did not require hospitalization (4/4) |
| 2 | Schauer et al.12 | n = 13/12–17 years | Pfizer (13/13), second (13/13) | Dyspnoea (5/13), fever (5/13), headache (5/13), arthralgia (6/13), nausea (1/13), vomiting (1/13), myalgia (7/13) | Raised CRP (3/13), raised Trop T (13/13) | ST elevation (8/13), nonspecific ST (1/13)/reduced EF (2/13) | LGE (4/4), no biopsy done | IVIg (3/13), symptomatic therapy (13/13) | Hospitalized and discharged (13/13) |
| 3 | Azir et al.13 | n = 1/17 years | Pfizer/second | Dyspnoea, chest pain | Raised Trop T | ST elevation/normal ECHO | LGE +, no biopsy done | Antiplatelet | Hospitalized and discharged |
| 4 | Wilson et al.14 | n = 1/16 years | Pfizer/second | Chest pain | Raised Trop T, raised BNP | Nonspecific ST-T changes/normal ECHO | LGE +, no biopsy done | NSAIDs | Recovered and did not require hospitalization |
| 5 | Mansour et al.15 | n = 2/21–25 years | Moderna/second | Fever (1/2), dyspnoea (1/2), chest pain (2/2), myalgia (1/2), headache (1/2) | Raised CRP (2/2), raised D-dimer (1/2), raised Trop I (2/2) | ST elevation (2/2)/reduced EF (1/2) | LGE + (2/2), no biopsy done | Managed conservatively | Recovered and did not require hospitalization (2/2) |
| 6 | Miqdad et al.16 | n = 1/18 years | Pfizer/second | Chest pain | Raised CRP, raised Trop I | ST elevation/normal ECHO | Myocardial oedema +, LGE +, no biopsy done | NSAIDs, colchicine, antiplatelet, ACEi/ARB | Hospitalized and discharged |
| 7 | Gautam et al.17 | n = 1/66 years | Pfizer/second | Palpitation, chest pain, nausea, vomiting, myalgia | Raised ESR, raised Trop I | Nonspecific ST-T changes, ECHO not done | LGE +, no biopsy done | Managed conservatively | Hospitalized and discharged |
| 8 | Das et al.18 | n = 25/12–17 years | Pfizer (25/25)/first dose (3/25), second dose (22/25) | Dyspnoea (3/25), fever (7/25), syncope (1/25), chest pain (25/25), nausea (2/25), vomiting (2/25), myalgia (3/25), headache (2/25), chills (1/25), sweating (1/25), shoulder and neck pain (1/25) | Raised CRP (10/17), raised Trop T (25/25) | ST elevation (14/25), T wave inversion (3/25), nonspecific ST-T changes (3/25), NSVT (3/25), VPC (1/25), ST depression (1/25), PR depression (1/25), first degree AV block with LBBB (1/25)/reduced EF (2/25) | Myocardial oedema (4/16), LGE + (16/16), no biopsy done | NSAIDs (23/24), Steroids (1/24), antiplatelet (1/24), diuretics (3/24), ACEi/ARB (2/24), IVIg (2/24) | Hospitalized and discharged (22/25), Recovered and did not require hospitalization (3/25) |
| 9 | Koizumi et al.19 | n = 2/22–27 years | Moderna/second | Chest pain (2/2) | Raised Trop T (2/2), raised CPK-MB (1/2) | ST elevation (2/2)/normal ECHO (2/2) | LGE (1/1), Biopsy—no specific findings (1/2), no inflammatory cell infiltrates (1/2) | NSAIDs (2/2) | Hospitalized and discharged (1/2), Recovered and did not require hospitalization (1/2) |
| 10 | Ujueta et al.20 | n = 1/62 years | Janssen/first | Myalgia | Positive procalcitonin, raised CRP, raised Trop I, raised Pro-BNP, raised AST, raised ALT | Sinus tachycardia, T inversion/reduced EF, RV dysfunction, pericardial effusion | MRI not reported, biopsy—lymphohistiocytic myocarditis with sparse eosinophils | Steroids, oxygen, ventilation, inotropes | Hospitalized and died |
| 11 | Nevet et al.21 | n = 3/20–29 years | Pfizer/second (3/3) | Fever (3/3), chest pain (3/3) | Raised CRP (1/1), raised Trop T/I (3/3) | ST elevation (3/3)/normal ECHO (3/3) | Myocardial oedema (3/3), LGE + (3/3), no biopsy done | NSAIDs (3/3), colchicine (3/3) | Hospitalized and discharged (3/3) |
| 12 | Cereda et al.22 | n = 1/21 years | Pfizer/second | Fever, chest pain | Raised Trop I | ST elevation, NSVT/LV hypokinesia | Myocardial oedema, LGE +, no biopsy done | Beta-blockers, ACEi/ARB, antibiotics | Hospitalized and discharged |
| 13 | Nguyen et al23 | n = 1/20 years | Moderna/first | Fever, chest pain, myalgia, chills | Thrombocytopenia, raised Trop T, raised Pro-BNP | Pre-excitation/reduced EF | Myocardial oedema, LGE +, biopsy—myocardial oedema and profound mononuclear infiltration | Not reported | Hospitalized and discharged |
| 14 | Watkins et al.24 | n = 1/20 years | Pfizer/second | Chest pain | Raised Trop T | ST elevation, PR depression/small pericardial effusion | MRI done—Myocardial oedema and LGE not reported, no biopsy done | NSAIDs, colchicine, beta-blocker | Hospitalized and discharged |
| 15 | Choi et al.25 | n = 1/22 years | Pfizer/first | Chest pain | Not reported | Ventricular fibrillation/ECHO not reported | MRI not reported, biopsy—diffuse inflammatory infiltration with neutrophils and histiocyte predominance | Not reported | Hospitalized and died |
| 16 | Rosner et al.26 | n = 7/19–39 years | Janssen (1/7), Pfizer (5/7), Moderna (1/7)/first dose (2/7), second dose (5/7) | Dyspnoea (2/7), fever (2/7), chest pain (7/7), myalgia (1/7), headache (1/7), chills (1/7), numbness and tingling (1/7) | Raised ESR (1/6), raised CRP (5/7), raised Trop I (7/7) | Sinus tachycardia (2/7), ST elevation (3/7), T inversion (1/7), nonspecific ST-T changes (1/7), PR depression (1/7)/reduced EF (4/7) | LGE + (7/7), no biopsy done | NSIADs (3/7), colchicine (3/7), steroids (1/7), beta-blockers (3/7), ACEi/ARB (2/7) | Hospitalized and discharged (7/7) |
| 17 | Chelala et al.27 | n = 5/16–19 years | Pfizer (4/5), Moderna (1/5)/second dose (5/5) | Chest pain (5/5) | Raised CRP (2/5), raised Trop I (5/5), raised BNP (1/1) | Sinus bradycardia (1/5), ST elevation (1/5)/reduced EF (1/5), LAD and RCA ectasia (1/5) | Myocardial oedema (4/5), LGE + (5/5), no biopsy done | NSIADs (1/5), colchicine (1/5), antiplatelet (1/5), beta-blocker (3/5) | Hospitalized and discharged (5/5) |
| 18 | Verma et al.28 | n = 2/42–45 years | Pfizer (1/2), Moderna (1/2)/ first dose (1/2), second dose (1/2) | Dyspnoea (2/2), fever (1/2), chest pain (1/2), dizziness (1/2) | Raised Trop I (2/2), raised Pro-BNP (1/1), raised AST (2/2), raised ALT (1/2), | Sinus tachycardia (1/2), ST elevation (1/2), ST depression (1/2)/reduced EF (2/2), pericardial effusion (2/2) | LGE + (1/1), Biopsy—inflammatory infiltrates (2/2) | NSAIDs (1/2), parenteral anticoagulant (2/2), steroids (2/2), antiplatelet (1/2), diuretics (2/2), beta-blockers (1/2), ACEi/ARB (1/2), antibiotics (2/2), oxygen (1/2), ventilation (1/2), inotropes (2/2) | Hospitalized and discharged (1/2), Hospitalized and died (1/2) |
| 19 | Fleming-Nouri et al.29 | n = 8/16–24 years | Pfizer (8/8)/second dose (8/8) | Chest pain (8/8) | Raised Trop T (1/1), raise Trop I (7/7) | ST elevation (7/8)/Mild LV hypokinesia (1/8) | LGE+ (3/5), no biopsy done | NSAIDs (5/5), steroids (4/5), antiplatelets (3/5), IVIg (4/5) | Hospitalized and discharged (8/8) |
| 20 | Shumkova et al.30 | n = 1/23 years | Pfizer/second | Dyspnoea, fever, chest pain | Raised CRP, raised CPK-MB, raised Trop T, raised Pro-BNP | Sinus tachycardia, ST elevation/reduced EF | LGE+, no biopsy done | NSAIDs, steroids, antibiotic | Hospitalized and discharged |
| 21 | Vollman et al.31 | n = 1/28 years | Pfizer/first | Fever, chest pain, myalgia | Raised CRP, raised Trop T | ST elevation/ECHO not done | LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 22 | Cimaglia et al.32 | n = 1/24 years | Pfizer/first | Chest pain | Raised CPK-MB, raised Trop T | Sinus tachycardia, ST elevation/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 23 | Patrignani et al.33 | n = 1/56 years | Pfizer/first | Abdominal pain, sweating | Raised Trop T | Normal ECG/normal ECHO | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 24 | Habib et al.34 | n = 1/37 years | Pfizer/second | Fever, chest pain, myalgia, joint pain, headache, chills | Raised Trop T | ST elevation/normal ECHO | LGE+, no biopsy done | Parenteral anticoagulant, antiplatelet, beta-blocker | Hospitalized and discharged |
| 25 | Schmitt et al.35 | n = 1/19 years | Pfizer/second | Chest pain, myalgia, headache | Raised CRP, raised Trop T | Sinus tachycardia, ST elevation/normal ECHO | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 26 | Alania-Torres et al.36 | n = 1/28 years | Pfizer/second | Dyspnoea, fever, chest pain, diarrhoea, myalgia, headache | Raised Trop I | Normal ECG/reduced EF | MRI not reported, no biopsy done | Colchicine, antiplatelet, diuretic, beta-blocker, ARNI | Hospitalized and discharged |
| 27 | Kim et al.37 | n = 1/24 years | Pfizer/second | Chest pain, myalgia | Raised CRP, raised Trop I | ST elevation/pericardial effusion | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 28 | Matta et al.38 | n = 1/27 years | Pfizer/second | Chest pain, myalgia | Thrombocytopenia, raised CRP, raised Trop I | Normal ECG/normal ECHO | MRI not reported, no biopsy done | NSAIDs | Hospitalized and discharged |
| 29 | Tiwari et al.39 | n = 1/33 years | Covaxin/first | Dyspnoea, oedema | Raised CPK-MB, raised AST, raised ALT | Sinus tachycardia/normal ECHO | Myocardial oedema +, no biopsy done | Steroid, beta-blocker | Recovered and did not require hospitalization |
| 30 | Mouch et al.40 | n = 6/16–45 years | Pfizer/first dose (1/6), second dose (5/6) | Chest pain (6/6) | Thrombocytopenia (1/6), raised CRP (5/6), raised Trop T (6/6), raised AST (4/6), raised ALT (1/6) | Sinus tachycardia (1/6), ST elevation (6/6), T inversion (3/6), PR depression (1/6)/reduced EF (2/6), minimal MR (1/6), minimal TR (1/6) | Myocardial oedema (4/6), LGE+ (6/6), no biopsy done | NSAIDs (6/6), colchicine (6/6) | Hospitalized and discharged (6/6) |
| 31 | Tailor et al.41 | n = 1/44 years | Moderna/second | Dyspnoea, chest pain | Raised CRP, raised Trop T, raised Pro-BNP | ST elevation/reduced EF | LGE+, no biopsy done | Colchicine, diuretics, beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 32 | Dickey et al.42 | n = 6/17–37 years | Pfizer (5/6), Modrna (1/6)/second dose (6/6) | Fever (3/6), chest pain (6/6), myalgia (4/6), headache (1/6), chills (1/6), rhinorrhoea (1/6) | Raised Trop T (6/6) | ST elevation (5/6), nonspecific ST-T changes (1/6), NSVT (1/6), PR depression (2/6)/reduced EF (5/6) | LGE+ (6/6), no biopsy done | Not reported | Hospitalized and discharged (6/6) |
| 33 | Sokolska et al.43 | n = 1/21 years | Pfizer/first | Chest pain | Raised CRP, raised Trop T, raised Pro-BNP | ST elevation, T inversion/normal ECHO | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 34 | Nassar et al.44 | n = 1/70 years | Janssen/first | Dyspnoea | Positive procalcitonin, raised CRP, raised Trop I | Sinus tachycardia, T inversion/reduced EF | MRI not reported, no biopsy done | Antibiotics, oxygen, ventilation, inotropes | Hospitalized and died |
| 35 | Montgomery et al.45 | n = 23/20–51 years | Pfizer (7/23), Moderna (16/23)/first dose (3/23), second dose (20/23) | Chest pain (23/23) | Raised Trop (23/23) | ST elevation (19/23), T inversion (19/23), nonspecific ST-T changes (19/23)/reduced EF (4/23) | Myocardial oedema (8/8), LGE+ (8/8), no biopsy done | Not reported | Hospitalized and discharged (23/23) |
| 36 | Minocha et al.46 | n = 1/17 years | Pfizer/second dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation/reduced EF | LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 37 | Starekova et al.47 | n = 5/17–38 years | Pfizer (3/5), Moderna (2/5)/ second dose (5/5) | Dyspnoea (2/5), fever (3/5), chest pain (5/5), nausea (2/5), myalgia (4/5), headache (2/5) | Raised Trop I (5/5) | ST elevation (2/5), T inversion (3/5)/reduced EF (3/5) | Myocardial oedema (5/5), LGE+ (5/5), no biopsy done | Not reported | Hospitalized and discharged (5/5) |
| 38 | Kim et al.48 | n = 4/23–70 years | Pfizer (2/4), Moderna (2/4),/ second dose (4/4) | Dyspnoea (3/4), fever (3/4), palpitations (1/4), syncope (1/4), chest pain (1/4), myalgia (3/4), headache (1/4), diaphoresis (1/4) | Raised ESR (1/3), raised CRP (2/3), raised Trop T (2/2), raised Trop I (2/2), raised Pro-BNP (2/3) | ST elevation (4/4), PR depression (2/4)/reduced EF (2/4) | LGE+ (4/4), no biopsy done | NSAIDs (2/4), colchicine (3/4), steroids (1/4) | Hospitalized and discharged (4/4) |
| 39 | Witberg et al.49 | n = 54/21–40 years | Pfizer (54/54)/second dose (54/54) | Fever (5/54), dyspnoea (3/54), palpitations (1/54), chest pain (44/54), myalgia (1/54) | Raised CRP (18/28), raised Trop T (41/41) | ST elevation (18/38), sinus tachycardia (1/38), T inversion (7/38), nonspecific ST-T changes (2/38), AF (1/38), NSVT (2/38)/reduced EF (14/48), pericardial effusion (10/48) | LGE+ (9/11), Biopsy—lymphocyte and eosinophil infiltration (1/1) | NSAIDs (12/54), colchicine (17/54), oral NOAC (1/54), steroid (1/54), antiplatelet (2/54), beta-blockers (20/54), ACEi/ARB (16/54), ECMO (1/54), inotropes (1/54), |
|
| 40 | Muthukumar et al.50 | n = 1/52 years | Moderna/second dose | Chest pain | Raised ESR, raised CRP, raised D-dimer, raised Trop T, raised AST, raised ALT | RBBB/normal ECHO | LGE+, no biopsy done | Beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 41 | Istampoulouoglou et al.51 | n = 14/17–88 years | Pfizer (4/14), Moderna (10/14)/first dose (5/14), second dose (9/14) | Dyspnoea (2/14), fever (2/14), palpitation (2/14), syncope (1/14), chest pain (9/14), abdominal pain (1/14), myalgia (1/14) | Raised Trop I (1/1), raised Trop T (11/12) | NSVT and SVT (1/10)/reduced EF (5/13) | Myocardial oedema (9/13), LGE+ (9/14), no biopsy done | NSAIDs (4/14), colchicine (2/14), diuretics (2/14), beta-blockers (6/14), ACEi/ARB (7/14), SGLT-2i (1/14), antibiotic (3/14) | Hospitalized and discharged (14/14) |
| 42 | Abbate et al.52 | n = 2/27–34 years | Pfizer (2/2)/first dose (1/2), second dose (1/2) | Fever (1/2), cough (1/2), chest pain (1/2), nausea (2/2), vomiting (2/2) | Raised CRP (2/2), raised D-dimer (1/2) | Sinus tachycardia (2/2), ST elevation (1/2), nonspecific ST-T changes (1/2)/reduced EF (2/2) | Myocardial oedema (1/1), LGE+ (1/1), no biopsy done | Steroids (2/2), IVIg (2/2), Anakinra (2/2), ECMO (2/2) | Hospitalized and discharged (1/2), hospitalized and died (1/2) |
| 43 | Viskin et al.53 | n = 8/20–34 years | Moderna (8/8)/second dose (8/8) | Chest pain (8/8), myalgia (8/8) | Raised Trop T (8/8) | ST elevation (5/8)/reduced EF (3/8) | LGE+ (6/8), no biopsy done | Not reported | Hospitalized and discharged (8/8) |
| 44 | Vidula et al.54 | n = 2/18–19 years | Pfizer (1/2), Moderna (1/2)/second dose (2/2) | Dyspnoea (1/2), fever (1/2), chest pain (2/2), myalgia (1/2) | Raised CRP (2/2), raised Trop T (2/2) | ST elevation (2/2), sinus tachycardia (1/2)/reduced EF (2/2) | Myocardial oedema (2/2), LGE+ (2/2), no biopsy done | NSAIDs (1/2), colchicine (1/2), beta-blockers (2/2), ACEi/ARB (1/2) | Hospitalized and discharged (2/2) |
| 45 | Chamling et al.55 | n = 3/20–68 years | Pfizer (2/3), Astra-Zeneca (1/3)/first dose (2/3), second dose (1/3) | Fever (1/3), chest pain (3/3), headache (1/3) | Raised CRP (1/3), raised Trop T (3/3) | ST elevation (2/3)/normal ECHO (3/3) | LGE+ (3/3), no biopsy done | Parenteral anticoagulant (1/3), antiplatelet (2/3), beta-blocker (1/3), ACEi/ARB (1/3) | Hospitalized (3/3). Outcome not reported |
| 46 | Albert et al.56 | n = 1/24 years | Moderna/second dose | Fever, chest pain, myalgia, chills | Raised Trop I | Normal ECG/normal ECHO | Myocardial oedema +, LGE +, no biopsy done | Beta-blocker | Hospitalized and discharged |
| 47 | Onderko et al.57 | n = 3/25–36 years | Pfizer (2/3), Moderna (1/3)/second dose (3/3) | Chest pain (3/3), myalgia (2/3), chills (1/3) | Raised CRP (2/2), raised Trop T (3/3) | ST elevation (2/3)/normal ECHO | Myocardial oedema (3/3), LGE+ (3/3), no biopsy done | NSAIDs (1/3), colchicine (1/3), beta-blockers (3/3) | Hospitalized and discharged (3/3) |
| 48 | Jain et al.58 | n = 63/12–20 years | Pfizer (59/63), Moderna (4/63)/first dose (1/63), second dose (62/63) | Dyspnoea (22/63), fever (28/63), chest pain (63/63), nausea (15/63), myalgia (24/63), headache (16/63) | Raised CRP (62/63), raised Trop T (63/63) | ST elevation (44/63), T inversion (44/63), NSVT (3/63), CHB (1/63)/reduced EF (9/63) | Myocardial odema (50/56), LGE+ (49/56), no biopsy done | NSAIDs (54/63), colchicine (4/63), steroid (15/63), antiplatelet (6/63), beta-blocker (6/63), IVIg (17/63) | Hospitalized and discharged (63/63) |
| 49 | Patel et al.59 | n = 5/19–37 years | Pfizer (4/5), Moderna (1/5)/first dose (1/5), second dose (4/5) | Dyspnoea (4/5), fever (1/5), chest pain (5/5), nausea (3/5), vomiting (1/5), myalgia (3/5), headache (3/5), chills (1/5), diaphoresis (1/5) | Raised ESR (1/4), raised CRP (3/3), raised Trop T (5/5) | Sinus tachycardia (1/5), ST elevation (1/5), PR depression (3/5), ST depression (1/5)/reduced EF (1/5) | Myocardial oedema (3/5), LGE+ (5/5), no biopsy done | NSAIDs (2/5), colchicine (4/5), antiplatelet (1/5), beta-blocker (1/5), ACEi/ARB (1/5) | Hospitalized and discharged (5/5) |
| 50 | Tano et al.60 | n = 8/15–18 years | Pfizer (8/8)/first dose (1/8), second dose (7/8) | Fever (1/8), palpitations (1/8), cough (1/8), chest pain (8/8), abdominal pain (1/8), diarrhoea (1/8), myalgia (2/8), headache (1/8) | Raised D-dimer (2/6), raised CPK-MB (3/5), raised Trop T (8/8) | ST elevation (4/8), PR depression (2/8), ST depression (2/8)/normal ECHO (8/8) | Myocardial oedema (3/3), LGE+ (3/3), no biopsy done | NSAIDs (5/8), IvIg (1/8) | Hospitalized and discharged (8/8) |
| 51 | Deb et al.61 | n = 1/67 years | Moderna/second dose | Dyspnoea, fever, PND, nausea, myalgia, chills | Raised ESR, raised CRP, raised Trop T, raised BNP | Sinus tachycardia, nonspecific ST-T changes/reduced EF | MRI not reported, no biopsy done | Diuretics, oxygen, HFNC/NIMV | Hospitalized and discharged |
| 52 | Marshall et al.62 | n = 7/14–19 years | Pfizer (7/7)/second dose (7/7) | Dyspnoea (3/7), fever (2/7), palpitation (1/7), chest pain (5/7), nausea (3/7), vomiting (2/7), myalgia (5/7), headache (1/7), chills (1/7), anorexia (1/7), paresthesia (1/7) | Raised ESR (3/7), raised CRP (4/7), raised Trop T (4/4), Trop I (3/3), raised Pro-BNP (3/4), raised AST (6/7), raised ALT (1/7) | Sinus bradycardia (1/7), ST elevation (6/7), T wave abnormalities (2/7), AV dissociation with junctional escape rhythm (1/7)/RV dysfunction (1/7), normal ECHO (7/7) | Myocardial oedema (6/7), LGE+ (6/7), no biopsy done | NSAIDs (6/7), Colchicine (1/7), steroids (4/7), antiplatelet (2/7), diuretics (1/7), IVIg (4/7), oxygen (1/7), HFNC/NIV (1/7) | Hospitalized and discharged (7/7) |
| 53 | Ambati et al.63 | n = 2/16–17 years | Pfizer (2/2)/second dose (2/2) | Dyspnoea (1 2), fever (1/2), chest pain (2/2), nausea (1/2), vomiting (1/2), myalgia (1/2), headache (1/2) | Raised ESR (1/2), raised CRP (1/2), raised D-dimer (1/2) Trop I (2/2) | ST elevation (2/2)/ECHO—not reported | MRI not reported, no biopsy done | NSAIDs (2/2) | Hospitalized and discharged (2/2) |
| 54 | Sulemankhil et al.64 | n = 1/33 years | Janssen/ first dose | Chest pain, myalgia, chills | Raised CRP, raised Trop T | ST elevation/reduced EF | LGE+, no biopsy done | Managed conservatively | Hospitalized and discharged |
| 55 | Simone et al.65 | n = 15/18–40 years | Pfizer (8/15) Moderna (7/15)/ first dose (2/15), second dose (13/15) | Chest pain (15/15) | Raised Trop I (15/15) | ST tachycardia (1/15), ST elevation (10/15), T inversion (1/15)/reduced EF (5/15) | MRI not reported, no biopsy done | Managed conservatively (15/15) | Hospitalized and discharged (15/15) |
| 56 | Ehrlich et al.66 | n = 1/40 years | Pfizer/first dose | Dyspnoea, fever, chest pain, headache | Raised CRP, raised Trop T, raised CPK-MB | ST elevation, ST depression/reduced EF | LGE+, biopsy—acute lymphocytic myocarditis | Parenteral anticoagulant, antiplatelet, beta-blocker, ACEi/ARB, ARNI | Hospitalized and discharged |
| 57 | Kaul et al.67 | n = 2/21–28 years | Pfizer (1/2), Moderna (1/2)/second dose (2/2) | Fever (2/2), chest pain (2/2), myalgia (1/2), headache (2/2), chills (1/2) | Raised CRP (2/2), raised D-dimer (1/2), Trop I (2/2) | ST elevation (2/2)/reduced EF (1/2) | LGE+ (2/2), no biopsy done | Colchicine (1/2), ACEi/ARB (1/2). ARNI (1/2) | Hospitalized and discharged (2/2) |
| 58 | Snapiri et al.68 | n = 7/16–18 years | Pfizer (7/7)/first dose (6/7), second dose (1/7) | Dyspnoea (2/7), fever (1/7), cough (1/7), chest pain (7/7), nausea (1/7), diarrhoea (1/7), headache (1/7) | Raised CRP (6/7), raised Trop T (7/7), raised Pro-BNP (3/4) | ST elevation (6/7), RBBB (1/7), ST depression (1/7), PR depression (1/7)/reduced EF (1/3), pericardial effusion (2/7) | MRI—not reported, no biopsy done | NSAIDs (5/7), antiplatelet (1/7), | Hospitalized and discharged (7/7) |
| 59 | Issak et al.69 | n = 1/15 years | Pfizer/second dose | Fever, myalgia, | Raised CRP, raised Trop T/I | ST elevation/normal ECHO | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 60 | Park et al.70 | n = 2/15–16 years | Pfizer (2/2)/first dose (1/2), second dose (1/2) | Fever (1/2), chest pain (2/2), headache (1/2) | Raised ESR (1/2), positive procalcitonin (1/2), raised Trop T (2/2), raised CPK-MB (2/2), raised Pro-BNP (2/2) | ST elevation (2/2), T-wave inversion (1/2)/reduced EF (1/2) | LGE+ (1/2), no biopsy done | Managed conservatively (2/2) | Hospitalized and discharged (2/2) |
| 61 | Diaz et al.71 | n = 20/median- 36 (26.3–48.3) years | Pfizer (9/20), Moderna (11/20)/first dose (4/20), second dose (16/20) | Chest pain (20/20) | Raised Trop T/I (19/20), raised AST (6/20), raised ALT (1/20) | ST elevation (9/20), PR depression (1/20), BBB (1/20)/reduced EF (5/20) | MRI—not reported, no biopsy done | NSAIDs (15/20), colchicine (9/20), diuretics (8/20), beta-blockers (8/20), ACEi/ARB (8/20) | Hospitalized and discharged (20/20) |
| 62 | Singh et al.72 | n = 1/24 years | Pfizer/second dose | Fever, chest pain, myalgia, headache, chills | Raised Trop I | ST depression/normal ECHO | LGE+, no biopsy done | Treatment not reported | Hospitalized and discharged |
| 63 | Chai et al.73 | n = 1/17 years | Pfizer/second dose | Dyspnoea, fever, chest pain, vomiting, diarrhoea, myalgia, headache, rash | Thrombocytopenia, positive procalcitonin, raised CRP, raised Trop T and Trop I, raised D-dimer, raised CPK-MB, | ECG—normal/reduced EF | LGE+, no biopsy done | Antibiotics, IVIg, oxygen, HFNC/NIV, inotropes | Hospitalized and discharged |
| 64 | Larson et al.74 | n = 8/21–40 years | Pfizer (5/8), Moderna (3/8) first dose (1/8), second dose (7/8) | Dyspnoea (1/8), fever (5/8), cough (1/8), chest pain (8/8), myalgia (2/8), chills (2/8) | Raised CRP (7/8), raised Trop T (8/8), raised Pro-BNP | ST elevation (6/8), aVR depression (2/8), ST depression (1/8), peaked T waves (1/8)/reduced EF (6/8) | Myocardial oedema (6/8), LGE+ (8/8), biopsy (1/1)—normal | NSAIDs (3/8), colchicine (2/8), steroids (2/8) | Hospitalized and discharged (8/8) |
| 65 | Williams et al.75 | n = 1/34 years | Moderna/second dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine, beta-blockers, ACEi/ARB | Hospitalized and discharged |
| 66 | McLean and Johnson76 | n = 1/16 years | Pfizer/second dose | Fever, chest pain, myalgia | Raised CRP, raised Trop T, raised CPK-MB, raised BNP | ST elevation/ECHO—not reported | Myocardial oedema, no biopsy done | NSAIDs, IVIg | Hospitalized and discharged |
| 67 | King et al.77 | n = 4/20–30 years | Pfizer (1/4), Moderna (3/4)/second dose (4/4) | Chest pain (4/4) | Raised CRP (3/4), raised Trop T (4/4) | ST elevation (3/4), T wave inversion (1/4), PR depression (3/4)/reduced EF (1/4) | LGE+ (1/1), no biopsy done | Treatment not reported | Hospitalized and discharged |
| 68 | Singh et al.78 | n = 2/52–65 years | ChAdOx1 (2/2)/first dose (1/2), second dose (1/2) | Dyspnoea (2/2), fever (1/2), cough (1/2), chest pain (1/2) | Raised CRP (2/2), raised Trop I (2/2), raised BNP (1/2), raised ALT (2/2) | Sinus tachycardia (1/2), ST depression (2/2)/pericardial effusion (1/2), reduced EF (2/2) | MRI—not reported, no biopsy done | Antiplatelet (2/2), diuretics (1/2), beta-blocker (1/2), ACEi/ARB (1/2), statin (1/2), nitrate (1/2), amlodipine (1/2) | Hospitalized and discharged (2/2) |
| 69 | Kim et al.79 | n = 1/29 years | Pfizer/second dose | Chest pain | Raised Trop I | ECG—normal/pericardial effusion, normal ECHO | MRI—not reported, no biopsy done | NSAIDs, steroids | Recovered and did not require hospitalization |
| 70 | D’Angelo et al.80 | n = 1/30 years | Pfizer/second dose | Dyspnoea, chest pain, nausea, sweating | Raised CRP, raised Trop T, raised CPK-MB | ST elevation, nonspecific ST-T changes/pericardial effusion, normal ECHO | LGE+, no biopsy done | NSAIDs, steroids, beta-blockers | Hospitalized and discharged |
| 71 | Sivakumaran et al.81 | n = 1/20 years | Pfizer/ second | Palpitation, chest pain | Raised Trop T, raised Pro-BNP | ST elevation/reduced EF | Myocardial oedema, LGE+, no biopsy done | Colchicine | Hospitalized and discharged |
| 72 | Pareek et al.82 | n = 11/16–53 years | Pfizer (9/11), Moderna (1/11), Ad26.COV2.S (1/11)/ first dose (1/11), second dose (10/11) | Dyspnoea (2/11), fever (7/11), palpitation (2/11), chest pain (10/11), nausea (2/11), abdominal pain (1/11), myalgia (8/11), headache (4/11), chills (2/11) | Raised CRP (6/11), raised Trop T (9/9), raised Trop I (2/2), raised Pro-BNP (3/7) | Sinus tachycardia (2/11), ST elevation (8/11), T inversion (1/11), PR depression (2/11), ST depression (1/11)/reduced EF (1/2), normal ECHO (1/2) | Myocardial oedema (4/9), LGE+ (8/9), no biopsy done | NSAIDs (11/11), colchicine (4/11), steroids (4/11), beta-blockers (3/11), ACEi/ARB (2/11), IVIg (4/11) | Hospitalized and discharged (11/11) |
| 73 | Walters et al.83 | n = 1/29 years | Pfizer/second dose | Chest pain, nausea | Raised Trop T | Sinus bradycardia, ST elevation/normal ECHO | MRI—not reported, no biopsy done | NSAIDs, colchicine, antiplatelet | Hospitalized and discharged |
| 74 | Hasnie et al.84 | n = 1/22 years | Moderna/first dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | LGE+, no biopsy done | NSAIDs, colchicine, antiplatelet, beta-blocker | Hospitalized and discharged |
| 75 | Khogali and Abdelrahman85 | n = 1/29 years | Moderna/second dose | Fever, nausea, vomiting, diarrhoea, myalgia | Raised D-dimer, raised Trop T, raised Pro-BNP | ST elevation, nonspecific ST-T waves, short PR interval/pericardial effusion, reduced EF | MRI—not done, no biopsy done | NSAIDs, colchicine, steroid, antiplatelet, inotrope | Hospitalized and discharged |
| 76 | Di Tano et al.86 | n = 1/29 years | Moderna/first dose | Fever, chest pain | Raised CRP, raised Trop T | ST elevation/ECHO—not reported | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine | Hospitalized and discharged |
| 77 | Maki et al.87 | n = 1/20 years | Moderna/second dose | Dyspnoea, fever, chest pain | Raised Trop I | Sinus tachycardia, ST elevation/pericardial effusion, reduced EF | LGE+, Biopsy—lymphocytic infiltration in myocardium | Diuretics, beta-blockers, inotrope, ACEi/ARB | Hospitalized and discharged |
| 78 | Ammirati et al.88 | n = 1/56 years | Pfizer/second dose | Chest pain | Raised D-dimer, raised CPK-MB, raised Trop T | ST elevation, peak T waves/ECHO—not reported | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine | Hospitalized and discharged |
| 79 | Rodriguez et al.89 | n = 1/68 years | AstraZeneca/first dose | Chest pain, sweating | Thrombocytopenia, raised CRP, raised Trop T | Atrial fibrillation/reduced EF | MRI—not reported, no biopsy done | Parenteral anticoagulant, inotrope | Hospitalized and discharged |
| 80 | Chen et al.90 | n = 1/16 years | Pfizer/first dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs, beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 81 | Hudson et al.91 | n = 2/22–24 years | Pfizer (2/2)/second dose (2/2) | Fever (2/2), chest pain (1/2), nausea (1/2), vomiting (1/2), myalgia (1/2), chills (2/2), substernal pain (1/2), diaphoresis (1/2) | Raised CRP (2/2), raised D-dimer (1/2), raised Trop T (2/2) | J point elevation (1/2), wide QRS complexes (1/2)/reduced EF (1/2) | MRI—nor reported, no biopsy done | NSAIDs (2/2), colchicine (2/2), antiplatelet (2/2) | Hospitalized and discharged (2/2) |
| 82 | Visclosky et al.92 | n = 1/15 years | Pfizer/second dose | Fever, chest pain, headache | Raised Trop T | ST elevation/reduced EF | MRI—not reported, no biopsy done | NSAIDs | Hospitalized and discharged |
| 83 | Dionne et al.93 | n = 15/29 years | Pfizer/first dose (1/15), second dose (14/15) | Fever (10/15), chest pain (15/15), palpitation (1/15), nausea (1/15), vomiting (1/15), myalgia (9/15), headache (6/15) | Raised CRP (8/14), raised Trop T (15/15) | ST elevation (9/15), T inversion (2/15), nonspecific ST-T changes (2/15), NSVT (1/15), PAC (1/15)/reduced EF (3/15) | Myocardial oedema (2/15), LGE+ (12/15), no biopsy done | Steroids (7/7), IVIg (7/7) | Hospitalized and discharged (15/15) |
| 84 | Oster et al.94 | n = 1626/21 years | Pfizer (490/1626) Moderna (1136/1626) first dose (273/1626); second dose (1265/1626); dose NA:(88/1626) | Dyspnoea (242/1626), palpitation (65/1626), chest pain (727/1626) | Raised Trop T/I (792/809) | ECG (569/794) Normal echo (598/721) LVEF normal (637/721) | Cardiac MRI (223/312), LGE: 223; oedema: 223, no biopsy done | Rx Received by 676/1626, NSAIDS (589/676), intravenous anticoagulant (54/676), steroids (81/676), diuretics (11/676), IVIg (78/676), antiarrhythmics (18/676), O2 (12/676), inotrope (12/676) | Hospitalized (784/813) |
| 85 | Truong et al.95 | n = 139/15.8 years | Pfizer: (131/139); Moderna: (5/139); J&J: (1/139); NR: (2/139); Dose 1: (12/139) Dose 2: (128/139) | Dyspnoea (38/139), fever (43/139), palpitation (7/139), chest pain (138/139), vomiting (17/139), diarrhoea (3/139), myalgia/fatigue (26/139), joint pain (22/139), rash (5/139) | Raised Trop T/I (139/139), raised BNP (101/139), raised NT pro BNP (8/139) |
|
| Rx by 139, NSAIDS (113/139), Colchicine (11/139), steroids (30/139), IVIg (30/139), Biologics given to 1 (Anakinra), 2 patients got inotropes. | Hospitalized and discharged (139/139). Hospital stay 2 days average and 26 were admitted to the ICU. Myocarditis was definite in 49 and probable in 91 |
ACEi, angiotensin-converting enzyme inhibitor; ALT, alanine transaminase; ARB, angiotensin II receptor blocker; AST, aspartate transaminase; BNP, B-type natriuretic peptide; CHB, complete heart block; CRP, C-reactive protein; EF, ejection fraction; ESR, erythrocyte sedimentation rate; ICU, intensive care unit; IL-6, interleukin-6; IvIg, intravenous immunoglobulin; LDH, lactate dehydrogenase; LGE, late gadolinium enhancement; NSAID, non steroidal anti-inflammatory drugs; NT Pro-BNP, N terminal Pro BNP; PAC, premature atrial contractions; Trop, troponin; VPC, ventricular premature complexes.
Table 1.
Summary of the studies reporting myocarditis after SARS-CoV-2 vaccination
| Sn | First author | Number of cases/age range | Vaccine/dose | Symptoms | Laboratory investigations | ECG/echocardiography | Cardiac imaging (LGE) and biopsy | Treatment | Outcomes |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Shaw et al.11 | n = 4/16–31 years | Pfizer (3/4), Moderna (1/4)/first dose (2/4), second dose (2/4) | Chest pain (4/4) | Raised Trop I (4/4) | ST elevation (1/4)/normal Echo (4/4) | LGE (4/4), no biopsy done | Treatment not reported | Recovered and did not require hospitalization (4/4) |
| 2 | Schauer et al.12 | n = 13/12–17 years | Pfizer (13/13), second (13/13) | Dyspnoea (5/13), fever (5/13), headache (5/13), arthralgia (6/13), nausea (1/13), vomiting (1/13), myalgia (7/13) | Raised CRP (3/13), raised Trop T (13/13) | ST elevation (8/13), nonspecific ST (1/13)/reduced EF (2/13) | LGE (4/4), no biopsy done | IVIg (3/13), symptomatic therapy (13/13) | Hospitalized and discharged (13/13) |
| 3 | Azir et al.13 | n = 1/17 years | Pfizer/second | Dyspnoea, chest pain | Raised Trop T | ST elevation/normal ECHO | LGE +, no biopsy done | Antiplatelet | Hospitalized and discharged |
| 4 | Wilson et al.14 | n = 1/16 years | Pfizer/second | Chest pain | Raised Trop T, raised BNP | Nonspecific ST-T changes/normal ECHO | LGE +, no biopsy done | NSAIDs | Recovered and did not require hospitalization |
| 5 | Mansour et al.15 | n = 2/21–25 years | Moderna/second | Fever (1/2), dyspnoea (1/2), chest pain (2/2), myalgia (1/2), headache (1/2) | Raised CRP (2/2), raised D-dimer (1/2), raised Trop I (2/2) | ST elevation (2/2)/reduced EF (1/2) | LGE + (2/2), no biopsy done | Managed conservatively | Recovered and did not require hospitalization (2/2) |
| 6 | Miqdad et al.16 | n = 1/18 years | Pfizer/second | Chest pain | Raised CRP, raised Trop I | ST elevation/normal ECHO | Myocardial oedema +, LGE +, no biopsy done | NSAIDs, colchicine, antiplatelet, ACEi/ARB | Hospitalized and discharged |
| 7 | Gautam et al.17 | n = 1/66 years | Pfizer/second | Palpitation, chest pain, nausea, vomiting, myalgia | Raised ESR, raised Trop I | Nonspecific ST-T changes, ECHO not done | LGE +, no biopsy done | Managed conservatively | Hospitalized and discharged |
| 8 | Das et al.18 | n = 25/12–17 years | Pfizer (25/25)/first dose (3/25), second dose (22/25) | Dyspnoea (3/25), fever (7/25), syncope (1/25), chest pain (25/25), nausea (2/25), vomiting (2/25), myalgia (3/25), headache (2/25), chills (1/25), sweating (1/25), shoulder and neck pain (1/25) | Raised CRP (10/17), raised Trop T (25/25) | ST elevation (14/25), T wave inversion (3/25), nonspecific ST-T changes (3/25), NSVT (3/25), VPC (1/25), ST depression (1/25), PR depression (1/25), first degree AV block with LBBB (1/25)/reduced EF (2/25) | Myocardial oedema (4/16), LGE + (16/16), no biopsy done | NSAIDs (23/24), Steroids (1/24), antiplatelet (1/24), diuretics (3/24), ACEi/ARB (2/24), IVIg (2/24) | Hospitalized and discharged (22/25), Recovered and did not require hospitalization (3/25) |
| 9 | Koizumi et al.19 | n = 2/22–27 years | Moderna/second | Chest pain (2/2) | Raised Trop T (2/2), raised CPK-MB (1/2) | ST elevation (2/2)/normal ECHO (2/2) | LGE (1/1), Biopsy—no specific findings (1/2), no inflammatory cell infiltrates (1/2) | NSAIDs (2/2) | Hospitalized and discharged (1/2), Recovered and did not require hospitalization (1/2) |
| 10 | Ujueta et al.20 | n = 1/62 years | Janssen/first | Myalgia | Positive procalcitonin, raised CRP, raised Trop I, raised Pro-BNP, raised AST, raised ALT | Sinus tachycardia, T inversion/reduced EF, RV dysfunction, pericardial effusion | MRI not reported, biopsy—lymphohistiocytic myocarditis with sparse eosinophils | Steroids, oxygen, ventilation, inotropes | Hospitalized and died |
| 11 | Nevet et al.21 | n = 3/20–29 years | Pfizer/second (3/3) | Fever (3/3), chest pain (3/3) | Raised CRP (1/1), raised Trop T/I (3/3) | ST elevation (3/3)/normal ECHO (3/3) | Myocardial oedema (3/3), LGE + (3/3), no biopsy done | NSAIDs (3/3), colchicine (3/3) | Hospitalized and discharged (3/3) |
| 12 | Cereda et al.22 | n = 1/21 years | Pfizer/second | Fever, chest pain | Raised Trop I | ST elevation, NSVT/LV hypokinesia | Myocardial oedema, LGE +, no biopsy done | Beta-blockers, ACEi/ARB, antibiotics | Hospitalized and discharged |
| 13 | Nguyen et al23 | n = 1/20 years | Moderna/first | Fever, chest pain, myalgia, chills | Thrombocytopenia, raised Trop T, raised Pro-BNP | Pre-excitation/reduced EF | Myocardial oedema, LGE +, biopsy—myocardial oedema and profound mononuclear infiltration | Not reported | Hospitalized and discharged |
| 14 | Watkins et al.24 | n = 1/20 years | Pfizer/second | Chest pain | Raised Trop T | ST elevation, PR depression/small pericardial effusion | MRI done—Myocardial oedema and LGE not reported, no biopsy done | NSAIDs, colchicine, beta-blocker | Hospitalized and discharged |
| 15 | Choi et al.25 | n = 1/22 years | Pfizer/first | Chest pain | Not reported | Ventricular fibrillation/ECHO not reported | MRI not reported, biopsy—diffuse inflammatory infiltration with neutrophils and histiocyte predominance | Not reported | Hospitalized and died |
| 16 | Rosner et al.26 | n = 7/19–39 years | Janssen (1/7), Pfizer (5/7), Moderna (1/7)/first dose (2/7), second dose (5/7) | Dyspnoea (2/7), fever (2/7), chest pain (7/7), myalgia (1/7), headache (1/7), chills (1/7), numbness and tingling (1/7) | Raised ESR (1/6), raised CRP (5/7), raised Trop I (7/7) | Sinus tachycardia (2/7), ST elevation (3/7), T inversion (1/7), nonspecific ST-T changes (1/7), PR depression (1/7)/reduced EF (4/7) | LGE + (7/7), no biopsy done | NSIADs (3/7), colchicine (3/7), steroids (1/7), beta-blockers (3/7), ACEi/ARB (2/7) | Hospitalized and discharged (7/7) |
| 17 | Chelala et al.27 | n = 5/16–19 years | Pfizer (4/5), Moderna (1/5)/second dose (5/5) | Chest pain (5/5) | Raised CRP (2/5), raised Trop I (5/5), raised BNP (1/1) | Sinus bradycardia (1/5), ST elevation (1/5)/reduced EF (1/5), LAD and RCA ectasia (1/5) | Myocardial oedema (4/5), LGE + (5/5), no biopsy done | NSIADs (1/5), colchicine (1/5), antiplatelet (1/5), beta-blocker (3/5) | Hospitalized and discharged (5/5) |
| 18 | Verma et al.28 | n = 2/42–45 years | Pfizer (1/2), Moderna (1/2)/ first dose (1/2), second dose (1/2) | Dyspnoea (2/2), fever (1/2), chest pain (1/2), dizziness (1/2) | Raised Trop I (2/2), raised Pro-BNP (1/1), raised AST (2/2), raised ALT (1/2), | Sinus tachycardia (1/2), ST elevation (1/2), ST depression (1/2)/reduced EF (2/2), pericardial effusion (2/2) | LGE + (1/1), Biopsy—inflammatory infiltrates (2/2) | NSAIDs (1/2), parenteral anticoagulant (2/2), steroids (2/2), antiplatelet (1/2), diuretics (2/2), beta-blockers (1/2), ACEi/ARB (1/2), antibiotics (2/2), oxygen (1/2), ventilation (1/2), inotropes (2/2) | Hospitalized and discharged (1/2), Hospitalized and died (1/2) |
| 19 | Fleming-Nouri et al.29 | n = 8/16–24 years | Pfizer (8/8)/second dose (8/8) | Chest pain (8/8) | Raised Trop T (1/1), raise Trop I (7/7) | ST elevation (7/8)/Mild LV hypokinesia (1/8) | LGE+ (3/5), no biopsy done | NSAIDs (5/5), steroids (4/5), antiplatelets (3/5), IVIg (4/5) | Hospitalized and discharged (8/8) |
| 20 | Shumkova et al.30 | n = 1/23 years | Pfizer/second | Dyspnoea, fever, chest pain | Raised CRP, raised CPK-MB, raised Trop T, raised Pro-BNP | Sinus tachycardia, ST elevation/reduced EF | LGE+, no biopsy done | NSAIDs, steroids, antibiotic | Hospitalized and discharged |
| 21 | Vollman et al.31 | n = 1/28 years | Pfizer/first | Fever, chest pain, myalgia | Raised CRP, raised Trop T | ST elevation/ECHO not done | LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 22 | Cimaglia et al.32 | n = 1/24 years | Pfizer/first | Chest pain | Raised CPK-MB, raised Trop T | Sinus tachycardia, ST elevation/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 23 | Patrignani et al.33 | n = 1/56 years | Pfizer/first | Abdominal pain, sweating | Raised Trop T | Normal ECG/normal ECHO | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 24 | Habib et al.34 | n = 1/37 years | Pfizer/second | Fever, chest pain, myalgia, joint pain, headache, chills | Raised Trop T | ST elevation/normal ECHO | LGE+, no biopsy done | Parenteral anticoagulant, antiplatelet, beta-blocker | Hospitalized and discharged |
| 25 | Schmitt et al.35 | n = 1/19 years | Pfizer/second | Chest pain, myalgia, headache | Raised CRP, raised Trop T | Sinus tachycardia, ST elevation/normal ECHO | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 26 | Alania-Torres et al.36 | n = 1/28 years | Pfizer/second | Dyspnoea, fever, chest pain, diarrhoea, myalgia, headache | Raised Trop I | Normal ECG/reduced EF | MRI not reported, no biopsy done | Colchicine, antiplatelet, diuretic, beta-blocker, ARNI | Hospitalized and discharged |
| 27 | Kim et al.37 | n = 1/24 years | Pfizer/second | Chest pain, myalgia | Raised CRP, raised Trop I | ST elevation/pericardial effusion | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 28 | Matta et al.38 | n = 1/27 years | Pfizer/second | Chest pain, myalgia | Thrombocytopenia, raised CRP, raised Trop I | Normal ECG/normal ECHO | MRI not reported, no biopsy done | NSAIDs | Hospitalized and discharged |
| 29 | Tiwari et al.39 | n = 1/33 years | Covaxin/first | Dyspnoea, oedema | Raised CPK-MB, raised AST, raised ALT | Sinus tachycardia/normal ECHO | Myocardial oedema +, no biopsy done | Steroid, beta-blocker | Recovered and did not require hospitalization |
| 30 | Mouch et al.40 | n = 6/16–45 years | Pfizer/first dose (1/6), second dose (5/6) | Chest pain (6/6) | Thrombocytopenia (1/6), raised CRP (5/6), raised Trop T (6/6), raised AST (4/6), raised ALT (1/6) | Sinus tachycardia (1/6), ST elevation (6/6), T inversion (3/6), PR depression (1/6)/reduced EF (2/6), minimal MR (1/6), minimal TR (1/6) | Myocardial oedema (4/6), LGE+ (6/6), no biopsy done | NSAIDs (6/6), colchicine (6/6) | Hospitalized and discharged (6/6) |
| 31 | Tailor et al.41 | n = 1/44 years | Moderna/second | Dyspnoea, chest pain | Raised CRP, raised Trop T, raised Pro-BNP | ST elevation/reduced EF | LGE+, no biopsy done | Colchicine, diuretics, beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 32 | Dickey et al.42 | n = 6/17–37 years | Pfizer (5/6), Modrna (1/6)/second dose (6/6) | Fever (3/6), chest pain (6/6), myalgia (4/6), headache (1/6), chills (1/6), rhinorrhoea (1/6) | Raised Trop T (6/6) | ST elevation (5/6), nonspecific ST-T changes (1/6), NSVT (1/6), PR depression (2/6)/reduced EF (5/6) | LGE+ (6/6), no biopsy done | Not reported | Hospitalized and discharged (6/6) |
| 33 | Sokolska et al.43 | n = 1/21 years | Pfizer/first | Chest pain | Raised CRP, raised Trop T, raised Pro-BNP | ST elevation, T inversion/normal ECHO | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 34 | Nassar et al.44 | n = 1/70 years | Janssen/first | Dyspnoea | Positive procalcitonin, raised CRP, raised Trop I | Sinus tachycardia, T inversion/reduced EF | MRI not reported, no biopsy done | Antibiotics, oxygen, ventilation, inotropes | Hospitalized and died |
| 35 | Montgomery et al.45 | n = 23/20–51 years | Pfizer (7/23), Moderna (16/23)/first dose (3/23), second dose (20/23) | Chest pain (23/23) | Raised Trop (23/23) | ST elevation (19/23), T inversion (19/23), nonspecific ST-T changes (19/23)/reduced EF (4/23) | Myocardial oedema (8/8), LGE+ (8/8), no biopsy done | Not reported | Hospitalized and discharged (23/23) |
| 36 | Minocha et al.46 | n = 1/17 years | Pfizer/second dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation/reduced EF | LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 37 | Starekova et al.47 | n = 5/17–38 years | Pfizer (3/5), Moderna (2/5)/ second dose (5/5) | Dyspnoea (2/5), fever (3/5), chest pain (5/5), nausea (2/5), myalgia (4/5), headache (2/5) | Raised Trop I (5/5) | ST elevation (2/5), T inversion (3/5)/reduced EF (3/5) | Myocardial oedema (5/5), LGE+ (5/5), no biopsy done | Not reported | Hospitalized and discharged (5/5) |
| 38 | Kim et al.48 | n = 4/23–70 years | Pfizer (2/4), Moderna (2/4),/ second dose (4/4) | Dyspnoea (3/4), fever (3/4), palpitations (1/4), syncope (1/4), chest pain (1/4), myalgia (3/4), headache (1/4), diaphoresis (1/4) | Raised ESR (1/3), raised CRP (2/3), raised Trop T (2/2), raised Trop I (2/2), raised Pro-BNP (2/3) | ST elevation (4/4), PR depression (2/4)/reduced EF (2/4) | LGE+ (4/4), no biopsy done | NSAIDs (2/4), colchicine (3/4), steroids (1/4) | Hospitalized and discharged (4/4) |
| 39 | Witberg et al.49 | n = 54/21–40 years | Pfizer (54/54)/second dose (54/54) | Fever (5/54), dyspnoea (3/54), palpitations (1/54), chest pain (44/54), myalgia (1/54) | Raised CRP (18/28), raised Trop T (41/41) | ST elevation (18/38), sinus tachycardia (1/38), T inversion (7/38), nonspecific ST-T changes (2/38), AF (1/38), NSVT (2/38)/reduced EF (14/48), pericardial effusion (10/48) | LGE+ (9/11), Biopsy—lymphocyte and eosinophil infiltration (1/1) | NSAIDs (12/54), colchicine (17/54), oral NOAC (1/54), steroid (1/54), antiplatelet (2/54), beta-blockers (20/54), ACEi/ARB (16/54), ECMO (1/54), inotropes (1/54), |
|
| 40 | Muthukumar et al.50 | n = 1/52 years | Moderna/second dose | Chest pain | Raised ESR, raised CRP, raised D-dimer, raised Trop T, raised AST, raised ALT | RBBB/normal ECHO | LGE+, no biopsy done | Beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 41 | Istampoulouoglou et al.51 | n = 14/17–88 years | Pfizer (4/14), Moderna (10/14)/first dose (5/14), second dose (9/14) | Dyspnoea (2/14), fever (2/14), palpitation (2/14), syncope (1/14), chest pain (9/14), abdominal pain (1/14), myalgia (1/14) | Raised Trop I (1/1), raised Trop T (11/12) | NSVT and SVT (1/10)/reduced EF (5/13) | Myocardial oedema (9/13), LGE+ (9/14), no biopsy done | NSAIDs (4/14), colchicine (2/14), diuretics (2/14), beta-blockers (6/14), ACEi/ARB (7/14), SGLT-2i (1/14), antibiotic (3/14) | Hospitalized and discharged (14/14) |
| 42 | Abbate et al.52 | n = 2/27–34 years | Pfizer (2/2)/first dose (1/2), second dose (1/2) | Fever (1/2), cough (1/2), chest pain (1/2), nausea (2/2), vomiting (2/2) | Raised CRP (2/2), raised D-dimer (1/2) | Sinus tachycardia (2/2), ST elevation (1/2), nonspecific ST-T changes (1/2)/reduced EF (2/2) | Myocardial oedema (1/1), LGE+ (1/1), no biopsy done | Steroids (2/2), IVIg (2/2), Anakinra (2/2), ECMO (2/2) | Hospitalized and discharged (1/2), hospitalized and died (1/2) |
| 43 | Viskin et al.53 | n = 8/20–34 years | Moderna (8/8)/second dose (8/8) | Chest pain (8/8), myalgia (8/8) | Raised Trop T (8/8) | ST elevation (5/8)/reduced EF (3/8) | LGE+ (6/8), no biopsy done | Not reported | Hospitalized and discharged (8/8) |
| 44 | Vidula et al.54 | n = 2/18–19 years | Pfizer (1/2), Moderna (1/2)/second dose (2/2) | Dyspnoea (1/2), fever (1/2), chest pain (2/2), myalgia (1/2) | Raised CRP (2/2), raised Trop T (2/2) | ST elevation (2/2), sinus tachycardia (1/2)/reduced EF (2/2) | Myocardial oedema (2/2), LGE+ (2/2), no biopsy done | NSAIDs (1/2), colchicine (1/2), beta-blockers (2/2), ACEi/ARB (1/2) | Hospitalized and discharged (2/2) |
| 45 | Chamling et al.55 | n = 3/20–68 years | Pfizer (2/3), Astra-Zeneca (1/3)/first dose (2/3), second dose (1/3) | Fever (1/3), chest pain (3/3), headache (1/3) | Raised CRP (1/3), raised Trop T (3/3) | ST elevation (2/3)/normal ECHO (3/3) | LGE+ (3/3), no biopsy done | Parenteral anticoagulant (1/3), antiplatelet (2/3), beta-blocker (1/3), ACEi/ARB (1/3) | Hospitalized (3/3). Outcome not reported |
| 46 | Albert et al.56 | n = 1/24 years | Moderna/second dose | Fever, chest pain, myalgia, chills | Raised Trop I | Normal ECG/normal ECHO | Myocardial oedema +, LGE +, no biopsy done | Beta-blocker | Hospitalized and discharged |
| 47 | Onderko et al.57 | n = 3/25–36 years | Pfizer (2/3), Moderna (1/3)/second dose (3/3) | Chest pain (3/3), myalgia (2/3), chills (1/3) | Raised CRP (2/2), raised Trop T (3/3) | ST elevation (2/3)/normal ECHO | Myocardial oedema (3/3), LGE+ (3/3), no biopsy done | NSAIDs (1/3), colchicine (1/3), beta-blockers (3/3) | Hospitalized and discharged (3/3) |
| 48 | Jain et al.58 | n = 63/12–20 years | Pfizer (59/63), Moderna (4/63)/first dose (1/63), second dose (62/63) | Dyspnoea (22/63), fever (28/63), chest pain (63/63), nausea (15/63), myalgia (24/63), headache (16/63) | Raised CRP (62/63), raised Trop T (63/63) | ST elevation (44/63), T inversion (44/63), NSVT (3/63), CHB (1/63)/reduced EF (9/63) | Myocardial odema (50/56), LGE+ (49/56), no biopsy done | NSAIDs (54/63), colchicine (4/63), steroid (15/63), antiplatelet (6/63), beta-blocker (6/63), IVIg (17/63) | Hospitalized and discharged (63/63) |
| 49 | Patel et al.59 | n = 5/19–37 years | Pfizer (4/5), Moderna (1/5)/first dose (1/5), second dose (4/5) | Dyspnoea (4/5), fever (1/5), chest pain (5/5), nausea (3/5), vomiting (1/5), myalgia (3/5), headache (3/5), chills (1/5), diaphoresis (1/5) | Raised ESR (1/4), raised CRP (3/3), raised Trop T (5/5) | Sinus tachycardia (1/5), ST elevation (1/5), PR depression (3/5), ST depression (1/5)/reduced EF (1/5) | Myocardial oedema (3/5), LGE+ (5/5), no biopsy done | NSAIDs (2/5), colchicine (4/5), antiplatelet (1/5), beta-blocker (1/5), ACEi/ARB (1/5) | Hospitalized and discharged (5/5) |
| 50 | Tano et al.60 | n = 8/15–18 years | Pfizer (8/8)/first dose (1/8), second dose (7/8) | Fever (1/8), palpitations (1/8), cough (1/8), chest pain (8/8), abdominal pain (1/8), diarrhoea (1/8), myalgia (2/8), headache (1/8) | Raised D-dimer (2/6), raised CPK-MB (3/5), raised Trop T (8/8) | ST elevation (4/8), PR depression (2/8), ST depression (2/8)/normal ECHO (8/8) | Myocardial oedema (3/3), LGE+ (3/3), no biopsy done | NSAIDs (5/8), IvIg (1/8) | Hospitalized and discharged (8/8) |
| 51 | Deb et al.61 | n = 1/67 years | Moderna/second dose | Dyspnoea, fever, PND, nausea, myalgia, chills | Raised ESR, raised CRP, raised Trop T, raised BNP | Sinus tachycardia, nonspecific ST-T changes/reduced EF | MRI not reported, no biopsy done | Diuretics, oxygen, HFNC/NIMV | Hospitalized and discharged |
| 52 | Marshall et al.62 | n = 7/14–19 years | Pfizer (7/7)/second dose (7/7) | Dyspnoea (3/7), fever (2/7), palpitation (1/7), chest pain (5/7), nausea (3/7), vomiting (2/7), myalgia (5/7), headache (1/7), chills (1/7), anorexia (1/7), paresthesia (1/7) | Raised ESR (3/7), raised CRP (4/7), raised Trop T (4/4), Trop I (3/3), raised Pro-BNP (3/4), raised AST (6/7), raised ALT (1/7) | Sinus bradycardia (1/7), ST elevation (6/7), T wave abnormalities (2/7), AV dissociation with junctional escape rhythm (1/7)/RV dysfunction (1/7), normal ECHO (7/7) | Myocardial oedema (6/7), LGE+ (6/7), no biopsy done | NSAIDs (6/7), Colchicine (1/7), steroids (4/7), antiplatelet (2/7), diuretics (1/7), IVIg (4/7), oxygen (1/7), HFNC/NIV (1/7) | Hospitalized and discharged (7/7) |
| 53 | Ambati et al.63 | n = 2/16–17 years | Pfizer (2/2)/second dose (2/2) | Dyspnoea (1 2), fever (1/2), chest pain (2/2), nausea (1/2), vomiting (1/2), myalgia (1/2), headache (1/2) | Raised ESR (1/2), raised CRP (1/2), raised D-dimer (1/2) Trop I (2/2) | ST elevation (2/2)/ECHO—not reported | MRI not reported, no biopsy done | NSAIDs (2/2) | Hospitalized and discharged (2/2) |
| 54 | Sulemankhil et al.64 | n = 1/33 years | Janssen/ first dose | Chest pain, myalgia, chills | Raised CRP, raised Trop T | ST elevation/reduced EF | LGE+, no biopsy done | Managed conservatively | Hospitalized and discharged |
| 55 | Simone et al.65 | n = 15/18–40 years | Pfizer (8/15) Moderna (7/15)/ first dose (2/15), second dose (13/15) | Chest pain (15/15) | Raised Trop I (15/15) | ST tachycardia (1/15), ST elevation (10/15), T inversion (1/15)/reduced EF (5/15) | MRI not reported, no biopsy done | Managed conservatively (15/15) | Hospitalized and discharged (15/15) |
| 56 | Ehrlich et al.66 | n = 1/40 years | Pfizer/first dose | Dyspnoea, fever, chest pain, headache | Raised CRP, raised Trop T, raised CPK-MB | ST elevation, ST depression/reduced EF | LGE+, biopsy—acute lymphocytic myocarditis | Parenteral anticoagulant, antiplatelet, beta-blocker, ACEi/ARB, ARNI | Hospitalized and discharged |
| 57 | Kaul et al.67 | n = 2/21–28 years | Pfizer (1/2), Moderna (1/2)/second dose (2/2) | Fever (2/2), chest pain (2/2), myalgia (1/2), headache (2/2), chills (1/2) | Raised CRP (2/2), raised D-dimer (1/2), Trop I (2/2) | ST elevation (2/2)/reduced EF (1/2) | LGE+ (2/2), no biopsy done | Colchicine (1/2), ACEi/ARB (1/2). ARNI (1/2) | Hospitalized and discharged (2/2) |
| 58 | Snapiri et al.68 | n = 7/16–18 years | Pfizer (7/7)/first dose (6/7), second dose (1/7) | Dyspnoea (2/7), fever (1/7), cough (1/7), chest pain (7/7), nausea (1/7), diarrhoea (1/7), headache (1/7) | Raised CRP (6/7), raised Trop T (7/7), raised Pro-BNP (3/4) | ST elevation (6/7), RBBB (1/7), ST depression (1/7), PR depression (1/7)/reduced EF (1/3), pericardial effusion (2/7) | MRI—not reported, no biopsy done | NSAIDs (5/7), antiplatelet (1/7), | Hospitalized and discharged (7/7) |
| 59 | Issak et al.69 | n = 1/15 years | Pfizer/second dose | Fever, myalgia, | Raised CRP, raised Trop T/I | ST elevation/normal ECHO | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 60 | Park et al.70 | n = 2/15–16 years | Pfizer (2/2)/first dose (1/2), second dose (1/2) | Fever (1/2), chest pain (2/2), headache (1/2) | Raised ESR (1/2), positive procalcitonin (1/2), raised Trop T (2/2), raised CPK-MB (2/2), raised Pro-BNP (2/2) | ST elevation (2/2), T-wave inversion (1/2)/reduced EF (1/2) | LGE+ (1/2), no biopsy done | Managed conservatively (2/2) | Hospitalized and discharged (2/2) |
| 61 | Diaz et al.71 | n = 20/median- 36 (26.3–48.3) years | Pfizer (9/20), Moderna (11/20)/first dose (4/20), second dose (16/20) | Chest pain (20/20) | Raised Trop T/I (19/20), raised AST (6/20), raised ALT (1/20) | ST elevation (9/20), PR depression (1/20), BBB (1/20)/reduced EF (5/20) | MRI—not reported, no biopsy done | NSAIDs (15/20), colchicine (9/20), diuretics (8/20), beta-blockers (8/20), ACEi/ARB (8/20) | Hospitalized and discharged (20/20) |
| 62 | Singh et al.72 | n = 1/24 years | Pfizer/second dose | Fever, chest pain, myalgia, headache, chills | Raised Trop I | ST depression/normal ECHO | LGE+, no biopsy done | Treatment not reported | Hospitalized and discharged |
| 63 | Chai et al.73 | n = 1/17 years | Pfizer/second dose | Dyspnoea, fever, chest pain, vomiting, diarrhoea, myalgia, headache, rash | Thrombocytopenia, positive procalcitonin, raised CRP, raised Trop T and Trop I, raised D-dimer, raised CPK-MB, | ECG—normal/reduced EF | LGE+, no biopsy done | Antibiotics, IVIg, oxygen, HFNC/NIV, inotropes | Hospitalized and discharged |
| 64 | Larson et al.74 | n = 8/21–40 years | Pfizer (5/8), Moderna (3/8) first dose (1/8), second dose (7/8) | Dyspnoea (1/8), fever (5/8), cough (1/8), chest pain (8/8), myalgia (2/8), chills (2/8) | Raised CRP (7/8), raised Trop T (8/8), raised Pro-BNP | ST elevation (6/8), aVR depression (2/8), ST depression (1/8), peaked T waves (1/8)/reduced EF (6/8) | Myocardial oedema (6/8), LGE+ (8/8), biopsy (1/1)—normal | NSAIDs (3/8), colchicine (2/8), steroids (2/8) | Hospitalized and discharged (8/8) |
| 65 | Williams et al.75 | n = 1/34 years | Moderna/second dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine, beta-blockers, ACEi/ARB | Hospitalized and discharged |
| 66 | McLean and Johnson76 | n = 1/16 years | Pfizer/second dose | Fever, chest pain, myalgia | Raised CRP, raised Trop T, raised CPK-MB, raised BNP | ST elevation/ECHO—not reported | Myocardial oedema, no biopsy done | NSAIDs, IVIg | Hospitalized and discharged |
| 67 | King et al.77 | n = 4/20–30 years | Pfizer (1/4), Moderna (3/4)/second dose (4/4) | Chest pain (4/4) | Raised CRP (3/4), raised Trop T (4/4) | ST elevation (3/4), T wave inversion (1/4), PR depression (3/4)/reduced EF (1/4) | LGE+ (1/1), no biopsy done | Treatment not reported | Hospitalized and discharged |
| 68 | Singh et al.78 | n = 2/52–65 years | ChAdOx1 (2/2)/first dose (1/2), second dose (1/2) | Dyspnoea (2/2), fever (1/2), cough (1/2), chest pain (1/2) | Raised CRP (2/2), raised Trop I (2/2), raised BNP (1/2), raised ALT (2/2) | Sinus tachycardia (1/2), ST depression (2/2)/pericardial effusion (1/2), reduced EF (2/2) | MRI—not reported, no biopsy done | Antiplatelet (2/2), diuretics (1/2), beta-blocker (1/2), ACEi/ARB (1/2), statin (1/2), nitrate (1/2), amlodipine (1/2) | Hospitalized and discharged (2/2) |
| 69 | Kim et al.79 | n = 1/29 years | Pfizer/second dose | Chest pain | Raised Trop I | ECG—normal/pericardial effusion, normal ECHO | MRI—not reported, no biopsy done | NSAIDs, steroids | Recovered and did not require hospitalization |
| 70 | D’Angelo et al.80 | n = 1/30 years | Pfizer/second dose | Dyspnoea, chest pain, nausea, sweating | Raised CRP, raised Trop T, raised CPK-MB | ST elevation, nonspecific ST-T changes/pericardial effusion, normal ECHO | LGE+, no biopsy done | NSAIDs, steroids, beta-blockers | Hospitalized and discharged |
| 71 | Sivakumaran et al.81 | n = 1/20 years | Pfizer/ second | Palpitation, chest pain | Raised Trop T, raised Pro-BNP | ST elevation/reduced EF | Myocardial oedema, LGE+, no biopsy done | Colchicine | Hospitalized and discharged |
| 72 | Pareek et al.82 | n = 11/16–53 years | Pfizer (9/11), Moderna (1/11), Ad26.COV2.S (1/11)/ first dose (1/11), second dose (10/11) | Dyspnoea (2/11), fever (7/11), palpitation (2/11), chest pain (10/11), nausea (2/11), abdominal pain (1/11), myalgia (8/11), headache (4/11), chills (2/11) | Raised CRP (6/11), raised Trop T (9/9), raised Trop I (2/2), raised Pro-BNP (3/7) | Sinus tachycardia (2/11), ST elevation (8/11), T inversion (1/11), PR depression (2/11), ST depression (1/11)/reduced EF (1/2), normal ECHO (1/2) | Myocardial oedema (4/9), LGE+ (8/9), no biopsy done | NSAIDs (11/11), colchicine (4/11), steroids (4/11), beta-blockers (3/11), ACEi/ARB (2/11), IVIg (4/11) | Hospitalized and discharged (11/11) |
| 73 | Walters et al.83 | n = 1/29 years | Pfizer/second dose | Chest pain, nausea | Raised Trop T | Sinus bradycardia, ST elevation/normal ECHO | MRI—not reported, no biopsy done | NSAIDs, colchicine, antiplatelet | Hospitalized and discharged |
| 74 | Hasnie et al.84 | n = 1/22 years | Moderna/first dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | LGE+, no biopsy done | NSAIDs, colchicine, antiplatelet, beta-blocker | Hospitalized and discharged |
| 75 | Khogali and Abdelrahman85 | n = 1/29 years | Moderna/second dose | Fever, nausea, vomiting, diarrhoea, myalgia | Raised D-dimer, raised Trop T, raised Pro-BNP | ST elevation, nonspecific ST-T waves, short PR interval/pericardial effusion, reduced EF | MRI—not done, no biopsy done | NSAIDs, colchicine, steroid, antiplatelet, inotrope | Hospitalized and discharged |
| 76 | Di Tano et al.86 | n = 1/29 years | Moderna/first dose | Fever, chest pain | Raised CRP, raised Trop T | ST elevation/ECHO—not reported | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine | Hospitalized and discharged |
| 77 | Maki et al.87 | n = 1/20 years | Moderna/second dose | Dyspnoea, fever, chest pain | Raised Trop I | Sinus tachycardia, ST elevation/pericardial effusion, reduced EF | LGE+, Biopsy—lymphocytic infiltration in myocardium | Diuretics, beta-blockers, inotrope, ACEi/ARB | Hospitalized and discharged |
| 78 | Ammirati et al.88 | n = 1/56 years | Pfizer/second dose | Chest pain | Raised D-dimer, raised CPK-MB, raised Trop T | ST elevation, peak T waves/ECHO—not reported | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine | Hospitalized and discharged |
| 79 | Rodriguez et al.89 | n = 1/68 years | AstraZeneca/first dose | Chest pain, sweating | Thrombocytopenia, raised CRP, raised Trop T | Atrial fibrillation/reduced EF | MRI—not reported, no biopsy done | Parenteral anticoagulant, inotrope | Hospitalized and discharged |
| 80 | Chen et al.90 | n = 1/16 years | Pfizer/first dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs, beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 81 | Hudson et al.91 | n = 2/22–24 years | Pfizer (2/2)/second dose (2/2) | Fever (2/2), chest pain (1/2), nausea (1/2), vomiting (1/2), myalgia (1/2), chills (2/2), substernal pain (1/2), diaphoresis (1/2) | Raised CRP (2/2), raised D-dimer (1/2), raised Trop T (2/2) | J point elevation (1/2), wide QRS complexes (1/2)/reduced EF (1/2) | MRI—nor reported, no biopsy done | NSAIDs (2/2), colchicine (2/2), antiplatelet (2/2) | Hospitalized and discharged (2/2) |
| 82 | Visclosky et al.92 | n = 1/15 years | Pfizer/second dose | Fever, chest pain, headache | Raised Trop T | ST elevation/reduced EF | MRI—not reported, no biopsy done | NSAIDs | Hospitalized and discharged |
| 83 | Dionne et al.93 | n = 15/29 years | Pfizer/first dose (1/15), second dose (14/15) | Fever (10/15), chest pain (15/15), palpitation (1/15), nausea (1/15), vomiting (1/15), myalgia (9/15), headache (6/15) | Raised CRP (8/14), raised Trop T (15/15) | ST elevation (9/15), T inversion (2/15), nonspecific ST-T changes (2/15), NSVT (1/15), PAC (1/15)/reduced EF (3/15) | Myocardial oedema (2/15), LGE+ (12/15), no biopsy done | Steroids (7/7), IVIg (7/7) | Hospitalized and discharged (15/15) |
| 84 | Oster et al.94 | n = 1626/21 years | Pfizer (490/1626) Moderna (1136/1626) first dose (273/1626); second dose (1265/1626); dose NA:(88/1626) | Dyspnoea (242/1626), palpitation (65/1626), chest pain (727/1626) | Raised Trop T/I (792/809) | ECG (569/794) Normal echo (598/721) LVEF normal (637/721) | Cardiac MRI (223/312), LGE: 223; oedema: 223, no biopsy done | Rx Received by 676/1626, NSAIDS (589/676), intravenous anticoagulant (54/676), steroids (81/676), diuretics (11/676), IVIg (78/676), antiarrhythmics (18/676), O2 (12/676), inotrope (12/676) | Hospitalized (784/813) |
| 85 | Truong et al.95 | n = 139/15.8 years | Pfizer: (131/139); Moderna: (5/139); J&J: (1/139); NR: (2/139); Dose 1: (12/139) Dose 2: (128/139) | Dyspnoea (38/139), fever (43/139), palpitation (7/139), chest pain (138/139), vomiting (17/139), diarrhoea (3/139), myalgia/fatigue (26/139), joint pain (22/139), rash (5/139) | Raised Trop T/I (139/139), raised BNP (101/139), raised NT pro BNP (8/139) |
|
| Rx by 139, NSAIDS (113/139), Colchicine (11/139), steroids (30/139), IVIg (30/139), Biologics given to 1 (Anakinra), 2 patients got inotropes. | Hospitalized and discharged (139/139). Hospital stay 2 days average and 26 were admitted to the ICU. Myocarditis was definite in 49 and probable in 91 |
| Sn | First author | Number of cases/age range | Vaccine/dose | Symptoms | Laboratory investigations | ECG/echocardiography | Cardiac imaging (LGE) and biopsy | Treatment | Outcomes |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Shaw et al.11 | n = 4/16–31 years | Pfizer (3/4), Moderna (1/4)/first dose (2/4), second dose (2/4) | Chest pain (4/4) | Raised Trop I (4/4) | ST elevation (1/4)/normal Echo (4/4) | LGE (4/4), no biopsy done | Treatment not reported | Recovered and did not require hospitalization (4/4) |
| 2 | Schauer et al.12 | n = 13/12–17 years | Pfizer (13/13), second (13/13) | Dyspnoea (5/13), fever (5/13), headache (5/13), arthralgia (6/13), nausea (1/13), vomiting (1/13), myalgia (7/13) | Raised CRP (3/13), raised Trop T (13/13) | ST elevation (8/13), nonspecific ST (1/13)/reduced EF (2/13) | LGE (4/4), no biopsy done | IVIg (3/13), symptomatic therapy (13/13) | Hospitalized and discharged (13/13) |
| 3 | Azir et al.13 | n = 1/17 years | Pfizer/second | Dyspnoea, chest pain | Raised Trop T | ST elevation/normal ECHO | LGE +, no biopsy done | Antiplatelet | Hospitalized and discharged |
| 4 | Wilson et al.14 | n = 1/16 years | Pfizer/second | Chest pain | Raised Trop T, raised BNP | Nonspecific ST-T changes/normal ECHO | LGE +, no biopsy done | NSAIDs | Recovered and did not require hospitalization |
| 5 | Mansour et al.15 | n = 2/21–25 years | Moderna/second | Fever (1/2), dyspnoea (1/2), chest pain (2/2), myalgia (1/2), headache (1/2) | Raised CRP (2/2), raised D-dimer (1/2), raised Trop I (2/2) | ST elevation (2/2)/reduced EF (1/2) | LGE + (2/2), no biopsy done | Managed conservatively | Recovered and did not require hospitalization (2/2) |
| 6 | Miqdad et al.16 | n = 1/18 years | Pfizer/second | Chest pain | Raised CRP, raised Trop I | ST elevation/normal ECHO | Myocardial oedema +, LGE +, no biopsy done | NSAIDs, colchicine, antiplatelet, ACEi/ARB | Hospitalized and discharged |
| 7 | Gautam et al.17 | n = 1/66 years | Pfizer/second | Palpitation, chest pain, nausea, vomiting, myalgia | Raised ESR, raised Trop I | Nonspecific ST-T changes, ECHO not done | LGE +, no biopsy done | Managed conservatively | Hospitalized and discharged |
| 8 | Das et al.18 | n = 25/12–17 years | Pfizer (25/25)/first dose (3/25), second dose (22/25) | Dyspnoea (3/25), fever (7/25), syncope (1/25), chest pain (25/25), nausea (2/25), vomiting (2/25), myalgia (3/25), headache (2/25), chills (1/25), sweating (1/25), shoulder and neck pain (1/25) | Raised CRP (10/17), raised Trop T (25/25) | ST elevation (14/25), T wave inversion (3/25), nonspecific ST-T changes (3/25), NSVT (3/25), VPC (1/25), ST depression (1/25), PR depression (1/25), first degree AV block with LBBB (1/25)/reduced EF (2/25) | Myocardial oedema (4/16), LGE + (16/16), no biopsy done | NSAIDs (23/24), Steroids (1/24), antiplatelet (1/24), diuretics (3/24), ACEi/ARB (2/24), IVIg (2/24) | Hospitalized and discharged (22/25), Recovered and did not require hospitalization (3/25) |
| 9 | Koizumi et al.19 | n = 2/22–27 years | Moderna/second | Chest pain (2/2) | Raised Trop T (2/2), raised CPK-MB (1/2) | ST elevation (2/2)/normal ECHO (2/2) | LGE (1/1), Biopsy—no specific findings (1/2), no inflammatory cell infiltrates (1/2) | NSAIDs (2/2) | Hospitalized and discharged (1/2), Recovered and did not require hospitalization (1/2) |
| 10 | Ujueta et al.20 | n = 1/62 years | Janssen/first | Myalgia | Positive procalcitonin, raised CRP, raised Trop I, raised Pro-BNP, raised AST, raised ALT | Sinus tachycardia, T inversion/reduced EF, RV dysfunction, pericardial effusion | MRI not reported, biopsy—lymphohistiocytic myocarditis with sparse eosinophils | Steroids, oxygen, ventilation, inotropes | Hospitalized and died |
| 11 | Nevet et al.21 | n = 3/20–29 years | Pfizer/second (3/3) | Fever (3/3), chest pain (3/3) | Raised CRP (1/1), raised Trop T/I (3/3) | ST elevation (3/3)/normal ECHO (3/3) | Myocardial oedema (3/3), LGE + (3/3), no biopsy done | NSAIDs (3/3), colchicine (3/3) | Hospitalized and discharged (3/3) |
| 12 | Cereda et al.22 | n = 1/21 years | Pfizer/second | Fever, chest pain | Raised Trop I | ST elevation, NSVT/LV hypokinesia | Myocardial oedema, LGE +, no biopsy done | Beta-blockers, ACEi/ARB, antibiotics | Hospitalized and discharged |
| 13 | Nguyen et al23 | n = 1/20 years | Moderna/first | Fever, chest pain, myalgia, chills | Thrombocytopenia, raised Trop T, raised Pro-BNP | Pre-excitation/reduced EF | Myocardial oedema, LGE +, biopsy—myocardial oedema and profound mononuclear infiltration | Not reported | Hospitalized and discharged |
| 14 | Watkins et al.24 | n = 1/20 years | Pfizer/second | Chest pain | Raised Trop T | ST elevation, PR depression/small pericardial effusion | MRI done—Myocardial oedema and LGE not reported, no biopsy done | NSAIDs, colchicine, beta-blocker | Hospitalized and discharged |
| 15 | Choi et al.25 | n = 1/22 years | Pfizer/first | Chest pain | Not reported | Ventricular fibrillation/ECHO not reported | MRI not reported, biopsy—diffuse inflammatory infiltration with neutrophils and histiocyte predominance | Not reported | Hospitalized and died |
| 16 | Rosner et al.26 | n = 7/19–39 years | Janssen (1/7), Pfizer (5/7), Moderna (1/7)/first dose (2/7), second dose (5/7) | Dyspnoea (2/7), fever (2/7), chest pain (7/7), myalgia (1/7), headache (1/7), chills (1/7), numbness and tingling (1/7) | Raised ESR (1/6), raised CRP (5/7), raised Trop I (7/7) | Sinus tachycardia (2/7), ST elevation (3/7), T inversion (1/7), nonspecific ST-T changes (1/7), PR depression (1/7)/reduced EF (4/7) | LGE + (7/7), no biopsy done | NSIADs (3/7), colchicine (3/7), steroids (1/7), beta-blockers (3/7), ACEi/ARB (2/7) | Hospitalized and discharged (7/7) |
| 17 | Chelala et al.27 | n = 5/16–19 years | Pfizer (4/5), Moderna (1/5)/second dose (5/5) | Chest pain (5/5) | Raised CRP (2/5), raised Trop I (5/5), raised BNP (1/1) | Sinus bradycardia (1/5), ST elevation (1/5)/reduced EF (1/5), LAD and RCA ectasia (1/5) | Myocardial oedema (4/5), LGE + (5/5), no biopsy done | NSIADs (1/5), colchicine (1/5), antiplatelet (1/5), beta-blocker (3/5) | Hospitalized and discharged (5/5) |
| 18 | Verma et al.28 | n = 2/42–45 years | Pfizer (1/2), Moderna (1/2)/ first dose (1/2), second dose (1/2) | Dyspnoea (2/2), fever (1/2), chest pain (1/2), dizziness (1/2) | Raised Trop I (2/2), raised Pro-BNP (1/1), raised AST (2/2), raised ALT (1/2), | Sinus tachycardia (1/2), ST elevation (1/2), ST depression (1/2)/reduced EF (2/2), pericardial effusion (2/2) | LGE + (1/1), Biopsy—inflammatory infiltrates (2/2) | NSAIDs (1/2), parenteral anticoagulant (2/2), steroids (2/2), antiplatelet (1/2), diuretics (2/2), beta-blockers (1/2), ACEi/ARB (1/2), antibiotics (2/2), oxygen (1/2), ventilation (1/2), inotropes (2/2) | Hospitalized and discharged (1/2), Hospitalized and died (1/2) |
| 19 | Fleming-Nouri et al.29 | n = 8/16–24 years | Pfizer (8/8)/second dose (8/8) | Chest pain (8/8) | Raised Trop T (1/1), raise Trop I (7/7) | ST elevation (7/8)/Mild LV hypokinesia (1/8) | LGE+ (3/5), no biopsy done | NSAIDs (5/5), steroids (4/5), antiplatelets (3/5), IVIg (4/5) | Hospitalized and discharged (8/8) |
| 20 | Shumkova et al.30 | n = 1/23 years | Pfizer/second | Dyspnoea, fever, chest pain | Raised CRP, raised CPK-MB, raised Trop T, raised Pro-BNP | Sinus tachycardia, ST elevation/reduced EF | LGE+, no biopsy done | NSAIDs, steroids, antibiotic | Hospitalized and discharged |
| 21 | Vollman et al.31 | n = 1/28 years | Pfizer/first | Fever, chest pain, myalgia | Raised CRP, raised Trop T | ST elevation/ECHO not done | LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 22 | Cimaglia et al.32 | n = 1/24 years | Pfizer/first | Chest pain | Raised CPK-MB, raised Trop T | Sinus tachycardia, ST elevation/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 23 | Patrignani et al.33 | n = 1/56 years | Pfizer/first | Abdominal pain, sweating | Raised Trop T | Normal ECG/normal ECHO | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 24 | Habib et al.34 | n = 1/37 years | Pfizer/second | Fever, chest pain, myalgia, joint pain, headache, chills | Raised Trop T | ST elevation/normal ECHO | LGE+, no biopsy done | Parenteral anticoagulant, antiplatelet, beta-blocker | Hospitalized and discharged |
| 25 | Schmitt et al.35 | n = 1/19 years | Pfizer/second | Chest pain, myalgia, headache | Raised CRP, raised Trop T | Sinus tachycardia, ST elevation/normal ECHO | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 26 | Alania-Torres et al.36 | n = 1/28 years | Pfizer/second | Dyspnoea, fever, chest pain, diarrhoea, myalgia, headache | Raised Trop I | Normal ECG/reduced EF | MRI not reported, no biopsy done | Colchicine, antiplatelet, diuretic, beta-blocker, ARNI | Hospitalized and discharged |
| 27 | Kim et al.37 | n = 1/24 years | Pfizer/second | Chest pain, myalgia | Raised CRP, raised Trop I | ST elevation/pericardial effusion | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 28 | Matta et al.38 | n = 1/27 years | Pfizer/second | Chest pain, myalgia | Thrombocytopenia, raised CRP, raised Trop I | Normal ECG/normal ECHO | MRI not reported, no biopsy done | NSAIDs | Hospitalized and discharged |
| 29 | Tiwari et al.39 | n = 1/33 years | Covaxin/first | Dyspnoea, oedema | Raised CPK-MB, raised AST, raised ALT | Sinus tachycardia/normal ECHO | Myocardial oedema +, no biopsy done | Steroid, beta-blocker | Recovered and did not require hospitalization |
| 30 | Mouch et al.40 | n = 6/16–45 years | Pfizer/first dose (1/6), second dose (5/6) | Chest pain (6/6) | Thrombocytopenia (1/6), raised CRP (5/6), raised Trop T (6/6), raised AST (4/6), raised ALT (1/6) | Sinus tachycardia (1/6), ST elevation (6/6), T inversion (3/6), PR depression (1/6)/reduced EF (2/6), minimal MR (1/6), minimal TR (1/6) | Myocardial oedema (4/6), LGE+ (6/6), no biopsy done | NSAIDs (6/6), colchicine (6/6) | Hospitalized and discharged (6/6) |
| 31 | Tailor et al.41 | n = 1/44 years | Moderna/second | Dyspnoea, chest pain | Raised CRP, raised Trop T, raised Pro-BNP | ST elevation/reduced EF | LGE+, no biopsy done | Colchicine, diuretics, beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 32 | Dickey et al.42 | n = 6/17–37 years | Pfizer (5/6), Modrna (1/6)/second dose (6/6) | Fever (3/6), chest pain (6/6), myalgia (4/6), headache (1/6), chills (1/6), rhinorrhoea (1/6) | Raised Trop T (6/6) | ST elevation (5/6), nonspecific ST-T changes (1/6), NSVT (1/6), PR depression (2/6)/reduced EF (5/6) | LGE+ (6/6), no biopsy done | Not reported | Hospitalized and discharged (6/6) |
| 33 | Sokolska et al.43 | n = 1/21 years | Pfizer/first | Chest pain | Raised CRP, raised Trop T, raised Pro-BNP | ST elevation, T inversion/normal ECHO | Myocardial oedema, LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 34 | Nassar et al.44 | n = 1/70 years | Janssen/first | Dyspnoea | Positive procalcitonin, raised CRP, raised Trop I | Sinus tachycardia, T inversion/reduced EF | MRI not reported, no biopsy done | Antibiotics, oxygen, ventilation, inotropes | Hospitalized and died |
| 35 | Montgomery et al.45 | n = 23/20–51 years | Pfizer (7/23), Moderna (16/23)/first dose (3/23), second dose (20/23) | Chest pain (23/23) | Raised Trop (23/23) | ST elevation (19/23), T inversion (19/23), nonspecific ST-T changes (19/23)/reduced EF (4/23) | Myocardial oedema (8/8), LGE+ (8/8), no biopsy done | Not reported | Hospitalized and discharged (23/23) |
| 36 | Minocha et al.46 | n = 1/17 years | Pfizer/second dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation/reduced EF | LGE+, no biopsy done | NSAIDs | Hospitalized and discharged |
| 37 | Starekova et al.47 | n = 5/17–38 years | Pfizer (3/5), Moderna (2/5)/ second dose (5/5) | Dyspnoea (2/5), fever (3/5), chest pain (5/5), nausea (2/5), myalgia (4/5), headache (2/5) | Raised Trop I (5/5) | ST elevation (2/5), T inversion (3/5)/reduced EF (3/5) | Myocardial oedema (5/5), LGE+ (5/5), no biopsy done | Not reported | Hospitalized and discharged (5/5) |
| 38 | Kim et al.48 | n = 4/23–70 years | Pfizer (2/4), Moderna (2/4),/ second dose (4/4) | Dyspnoea (3/4), fever (3/4), palpitations (1/4), syncope (1/4), chest pain (1/4), myalgia (3/4), headache (1/4), diaphoresis (1/4) | Raised ESR (1/3), raised CRP (2/3), raised Trop T (2/2), raised Trop I (2/2), raised Pro-BNP (2/3) | ST elevation (4/4), PR depression (2/4)/reduced EF (2/4) | LGE+ (4/4), no biopsy done | NSAIDs (2/4), colchicine (3/4), steroids (1/4) | Hospitalized and discharged (4/4) |
| 39 | Witberg et al.49 | n = 54/21–40 years | Pfizer (54/54)/second dose (54/54) | Fever (5/54), dyspnoea (3/54), palpitations (1/54), chest pain (44/54), myalgia (1/54) | Raised CRP (18/28), raised Trop T (41/41) | ST elevation (18/38), sinus tachycardia (1/38), T inversion (7/38), nonspecific ST-T changes (2/38), AF (1/38), NSVT (2/38)/reduced EF (14/48), pericardial effusion (10/48) | LGE+ (9/11), Biopsy—lymphocyte and eosinophil infiltration (1/1) | NSAIDs (12/54), colchicine (17/54), oral NOAC (1/54), steroid (1/54), antiplatelet (2/54), beta-blockers (20/54), ACEi/ARB (16/54), ECMO (1/54), inotropes (1/54), |
|
| 40 | Muthukumar et al.50 | n = 1/52 years | Moderna/second dose | Chest pain | Raised ESR, raised CRP, raised D-dimer, raised Trop T, raised AST, raised ALT | RBBB/normal ECHO | LGE+, no biopsy done | Beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 41 | Istampoulouoglou et al.51 | n = 14/17–88 years | Pfizer (4/14), Moderna (10/14)/first dose (5/14), second dose (9/14) | Dyspnoea (2/14), fever (2/14), palpitation (2/14), syncope (1/14), chest pain (9/14), abdominal pain (1/14), myalgia (1/14) | Raised Trop I (1/1), raised Trop T (11/12) | NSVT and SVT (1/10)/reduced EF (5/13) | Myocardial oedema (9/13), LGE+ (9/14), no biopsy done | NSAIDs (4/14), colchicine (2/14), diuretics (2/14), beta-blockers (6/14), ACEi/ARB (7/14), SGLT-2i (1/14), antibiotic (3/14) | Hospitalized and discharged (14/14) |
| 42 | Abbate et al.52 | n = 2/27–34 years | Pfizer (2/2)/first dose (1/2), second dose (1/2) | Fever (1/2), cough (1/2), chest pain (1/2), nausea (2/2), vomiting (2/2) | Raised CRP (2/2), raised D-dimer (1/2) | Sinus tachycardia (2/2), ST elevation (1/2), nonspecific ST-T changes (1/2)/reduced EF (2/2) | Myocardial oedema (1/1), LGE+ (1/1), no biopsy done | Steroids (2/2), IVIg (2/2), Anakinra (2/2), ECMO (2/2) | Hospitalized and discharged (1/2), hospitalized and died (1/2) |
| 43 | Viskin et al.53 | n = 8/20–34 years | Moderna (8/8)/second dose (8/8) | Chest pain (8/8), myalgia (8/8) | Raised Trop T (8/8) | ST elevation (5/8)/reduced EF (3/8) | LGE+ (6/8), no biopsy done | Not reported | Hospitalized and discharged (8/8) |
| 44 | Vidula et al.54 | n = 2/18–19 years | Pfizer (1/2), Moderna (1/2)/second dose (2/2) | Dyspnoea (1/2), fever (1/2), chest pain (2/2), myalgia (1/2) | Raised CRP (2/2), raised Trop T (2/2) | ST elevation (2/2), sinus tachycardia (1/2)/reduced EF (2/2) | Myocardial oedema (2/2), LGE+ (2/2), no biopsy done | NSAIDs (1/2), colchicine (1/2), beta-blockers (2/2), ACEi/ARB (1/2) | Hospitalized and discharged (2/2) |
| 45 | Chamling et al.55 | n = 3/20–68 years | Pfizer (2/3), Astra-Zeneca (1/3)/first dose (2/3), second dose (1/3) | Fever (1/3), chest pain (3/3), headache (1/3) | Raised CRP (1/3), raised Trop T (3/3) | ST elevation (2/3)/normal ECHO (3/3) | LGE+ (3/3), no biopsy done | Parenteral anticoagulant (1/3), antiplatelet (2/3), beta-blocker (1/3), ACEi/ARB (1/3) | Hospitalized (3/3). Outcome not reported |
| 46 | Albert et al.56 | n = 1/24 years | Moderna/second dose | Fever, chest pain, myalgia, chills | Raised Trop I | Normal ECG/normal ECHO | Myocardial oedema +, LGE +, no biopsy done | Beta-blocker | Hospitalized and discharged |
| 47 | Onderko et al.57 | n = 3/25–36 years | Pfizer (2/3), Moderna (1/3)/second dose (3/3) | Chest pain (3/3), myalgia (2/3), chills (1/3) | Raised CRP (2/2), raised Trop T (3/3) | ST elevation (2/3)/normal ECHO | Myocardial oedema (3/3), LGE+ (3/3), no biopsy done | NSAIDs (1/3), colchicine (1/3), beta-blockers (3/3) | Hospitalized and discharged (3/3) |
| 48 | Jain et al.58 | n = 63/12–20 years | Pfizer (59/63), Moderna (4/63)/first dose (1/63), second dose (62/63) | Dyspnoea (22/63), fever (28/63), chest pain (63/63), nausea (15/63), myalgia (24/63), headache (16/63) | Raised CRP (62/63), raised Trop T (63/63) | ST elevation (44/63), T inversion (44/63), NSVT (3/63), CHB (1/63)/reduced EF (9/63) | Myocardial odema (50/56), LGE+ (49/56), no biopsy done | NSAIDs (54/63), colchicine (4/63), steroid (15/63), antiplatelet (6/63), beta-blocker (6/63), IVIg (17/63) | Hospitalized and discharged (63/63) |
| 49 | Patel et al.59 | n = 5/19–37 years | Pfizer (4/5), Moderna (1/5)/first dose (1/5), second dose (4/5) | Dyspnoea (4/5), fever (1/5), chest pain (5/5), nausea (3/5), vomiting (1/5), myalgia (3/5), headache (3/5), chills (1/5), diaphoresis (1/5) | Raised ESR (1/4), raised CRP (3/3), raised Trop T (5/5) | Sinus tachycardia (1/5), ST elevation (1/5), PR depression (3/5), ST depression (1/5)/reduced EF (1/5) | Myocardial oedema (3/5), LGE+ (5/5), no biopsy done | NSAIDs (2/5), colchicine (4/5), antiplatelet (1/5), beta-blocker (1/5), ACEi/ARB (1/5) | Hospitalized and discharged (5/5) |
| 50 | Tano et al.60 | n = 8/15–18 years | Pfizer (8/8)/first dose (1/8), second dose (7/8) | Fever (1/8), palpitations (1/8), cough (1/8), chest pain (8/8), abdominal pain (1/8), diarrhoea (1/8), myalgia (2/8), headache (1/8) | Raised D-dimer (2/6), raised CPK-MB (3/5), raised Trop T (8/8) | ST elevation (4/8), PR depression (2/8), ST depression (2/8)/normal ECHO (8/8) | Myocardial oedema (3/3), LGE+ (3/3), no biopsy done | NSAIDs (5/8), IvIg (1/8) | Hospitalized and discharged (8/8) |
| 51 | Deb et al.61 | n = 1/67 years | Moderna/second dose | Dyspnoea, fever, PND, nausea, myalgia, chills | Raised ESR, raised CRP, raised Trop T, raised BNP | Sinus tachycardia, nonspecific ST-T changes/reduced EF | MRI not reported, no biopsy done | Diuretics, oxygen, HFNC/NIMV | Hospitalized and discharged |
| 52 | Marshall et al.62 | n = 7/14–19 years | Pfizer (7/7)/second dose (7/7) | Dyspnoea (3/7), fever (2/7), palpitation (1/7), chest pain (5/7), nausea (3/7), vomiting (2/7), myalgia (5/7), headache (1/7), chills (1/7), anorexia (1/7), paresthesia (1/7) | Raised ESR (3/7), raised CRP (4/7), raised Trop T (4/4), Trop I (3/3), raised Pro-BNP (3/4), raised AST (6/7), raised ALT (1/7) | Sinus bradycardia (1/7), ST elevation (6/7), T wave abnormalities (2/7), AV dissociation with junctional escape rhythm (1/7)/RV dysfunction (1/7), normal ECHO (7/7) | Myocardial oedema (6/7), LGE+ (6/7), no biopsy done | NSAIDs (6/7), Colchicine (1/7), steroids (4/7), antiplatelet (2/7), diuretics (1/7), IVIg (4/7), oxygen (1/7), HFNC/NIV (1/7) | Hospitalized and discharged (7/7) |
| 53 | Ambati et al.63 | n = 2/16–17 years | Pfizer (2/2)/second dose (2/2) | Dyspnoea (1 2), fever (1/2), chest pain (2/2), nausea (1/2), vomiting (1/2), myalgia (1/2), headache (1/2) | Raised ESR (1/2), raised CRP (1/2), raised D-dimer (1/2) Trop I (2/2) | ST elevation (2/2)/ECHO—not reported | MRI not reported, no biopsy done | NSAIDs (2/2) | Hospitalized and discharged (2/2) |
| 54 | Sulemankhil et al.64 | n = 1/33 years | Janssen/ first dose | Chest pain, myalgia, chills | Raised CRP, raised Trop T | ST elevation/reduced EF | LGE+, no biopsy done | Managed conservatively | Hospitalized and discharged |
| 55 | Simone et al.65 | n = 15/18–40 years | Pfizer (8/15) Moderna (7/15)/ first dose (2/15), second dose (13/15) | Chest pain (15/15) | Raised Trop I (15/15) | ST tachycardia (1/15), ST elevation (10/15), T inversion (1/15)/reduced EF (5/15) | MRI not reported, no biopsy done | Managed conservatively (15/15) | Hospitalized and discharged (15/15) |
| 56 | Ehrlich et al.66 | n = 1/40 years | Pfizer/first dose | Dyspnoea, fever, chest pain, headache | Raised CRP, raised Trop T, raised CPK-MB | ST elevation, ST depression/reduced EF | LGE+, biopsy—acute lymphocytic myocarditis | Parenteral anticoagulant, antiplatelet, beta-blocker, ACEi/ARB, ARNI | Hospitalized and discharged |
| 57 | Kaul et al.67 | n = 2/21–28 years | Pfizer (1/2), Moderna (1/2)/second dose (2/2) | Fever (2/2), chest pain (2/2), myalgia (1/2), headache (2/2), chills (1/2) | Raised CRP (2/2), raised D-dimer (1/2), Trop I (2/2) | ST elevation (2/2)/reduced EF (1/2) | LGE+ (2/2), no biopsy done | Colchicine (1/2), ACEi/ARB (1/2). ARNI (1/2) | Hospitalized and discharged (2/2) |
| 58 | Snapiri et al.68 | n = 7/16–18 years | Pfizer (7/7)/first dose (6/7), second dose (1/7) | Dyspnoea (2/7), fever (1/7), cough (1/7), chest pain (7/7), nausea (1/7), diarrhoea (1/7), headache (1/7) | Raised CRP (6/7), raised Trop T (7/7), raised Pro-BNP (3/4) | ST elevation (6/7), RBBB (1/7), ST depression (1/7), PR depression (1/7)/reduced EF (1/3), pericardial effusion (2/7) | MRI—not reported, no biopsy done | NSAIDs (5/7), antiplatelet (1/7), | Hospitalized and discharged (7/7) |
| 59 | Issak et al.69 | n = 1/15 years | Pfizer/second dose | Fever, myalgia, | Raised CRP, raised Trop T/I | ST elevation/normal ECHO | Myocardial oedema, LGE+, no biopsy done | Not reported | Hospitalized and discharged |
| 60 | Park et al.70 | n = 2/15–16 years | Pfizer (2/2)/first dose (1/2), second dose (1/2) | Fever (1/2), chest pain (2/2), headache (1/2) | Raised ESR (1/2), positive procalcitonin (1/2), raised Trop T (2/2), raised CPK-MB (2/2), raised Pro-BNP (2/2) | ST elevation (2/2), T-wave inversion (1/2)/reduced EF (1/2) | LGE+ (1/2), no biopsy done | Managed conservatively (2/2) | Hospitalized and discharged (2/2) |
| 61 | Diaz et al.71 | n = 20/median- 36 (26.3–48.3) years | Pfizer (9/20), Moderna (11/20)/first dose (4/20), second dose (16/20) | Chest pain (20/20) | Raised Trop T/I (19/20), raised AST (6/20), raised ALT (1/20) | ST elevation (9/20), PR depression (1/20), BBB (1/20)/reduced EF (5/20) | MRI—not reported, no biopsy done | NSAIDs (15/20), colchicine (9/20), diuretics (8/20), beta-blockers (8/20), ACEi/ARB (8/20) | Hospitalized and discharged (20/20) |
| 62 | Singh et al.72 | n = 1/24 years | Pfizer/second dose | Fever, chest pain, myalgia, headache, chills | Raised Trop I | ST depression/normal ECHO | LGE+, no biopsy done | Treatment not reported | Hospitalized and discharged |
| 63 | Chai et al.73 | n = 1/17 years | Pfizer/second dose | Dyspnoea, fever, chest pain, vomiting, diarrhoea, myalgia, headache, rash | Thrombocytopenia, positive procalcitonin, raised CRP, raised Trop T and Trop I, raised D-dimer, raised CPK-MB, | ECG—normal/reduced EF | LGE+, no biopsy done | Antibiotics, IVIg, oxygen, HFNC/NIV, inotropes | Hospitalized and discharged |
| 64 | Larson et al.74 | n = 8/21–40 years | Pfizer (5/8), Moderna (3/8) first dose (1/8), second dose (7/8) | Dyspnoea (1/8), fever (5/8), cough (1/8), chest pain (8/8), myalgia (2/8), chills (2/8) | Raised CRP (7/8), raised Trop T (8/8), raised Pro-BNP | ST elevation (6/8), aVR depression (2/8), ST depression (1/8), peaked T waves (1/8)/reduced EF (6/8) | Myocardial oedema (6/8), LGE+ (8/8), biopsy (1/1)—normal | NSAIDs (3/8), colchicine (2/8), steroids (2/8) | Hospitalized and discharged (8/8) |
| 65 | Williams et al.75 | n = 1/34 years | Moderna/second dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine, beta-blockers, ACEi/ARB | Hospitalized and discharged |
| 66 | McLean and Johnson76 | n = 1/16 years | Pfizer/second dose | Fever, chest pain, myalgia | Raised CRP, raised Trop T, raised CPK-MB, raised BNP | ST elevation/ECHO—not reported | Myocardial oedema, no biopsy done | NSAIDs, IVIg | Hospitalized and discharged |
| 67 | King et al.77 | n = 4/20–30 years | Pfizer (1/4), Moderna (3/4)/second dose (4/4) | Chest pain (4/4) | Raised CRP (3/4), raised Trop T (4/4) | ST elevation (3/4), T wave inversion (1/4), PR depression (3/4)/reduced EF (1/4) | LGE+ (1/1), no biopsy done | Treatment not reported | Hospitalized and discharged |
| 68 | Singh et al.78 | n = 2/52–65 years | ChAdOx1 (2/2)/first dose (1/2), second dose (1/2) | Dyspnoea (2/2), fever (1/2), cough (1/2), chest pain (1/2) | Raised CRP (2/2), raised Trop I (2/2), raised BNP (1/2), raised ALT (2/2) | Sinus tachycardia (1/2), ST depression (2/2)/pericardial effusion (1/2), reduced EF (2/2) | MRI—not reported, no biopsy done | Antiplatelet (2/2), diuretics (1/2), beta-blocker (1/2), ACEi/ARB (1/2), statin (1/2), nitrate (1/2), amlodipine (1/2) | Hospitalized and discharged (2/2) |
| 69 | Kim et al.79 | n = 1/29 years | Pfizer/second dose | Chest pain | Raised Trop I | ECG—normal/pericardial effusion, normal ECHO | MRI—not reported, no biopsy done | NSAIDs, steroids | Recovered and did not require hospitalization |
| 70 | D’Angelo et al.80 | n = 1/30 years | Pfizer/second dose | Dyspnoea, chest pain, nausea, sweating | Raised CRP, raised Trop T, raised CPK-MB | ST elevation, nonspecific ST-T changes/pericardial effusion, normal ECHO | LGE+, no biopsy done | NSAIDs, steroids, beta-blockers | Hospitalized and discharged |
| 71 | Sivakumaran et al.81 | n = 1/20 years | Pfizer/ second | Palpitation, chest pain | Raised Trop T, raised Pro-BNP | ST elevation/reduced EF | Myocardial oedema, LGE+, no biopsy done | Colchicine | Hospitalized and discharged |
| 72 | Pareek et al.82 | n = 11/16–53 years | Pfizer (9/11), Moderna (1/11), Ad26.COV2.S (1/11)/ first dose (1/11), second dose (10/11) | Dyspnoea (2/11), fever (7/11), palpitation (2/11), chest pain (10/11), nausea (2/11), abdominal pain (1/11), myalgia (8/11), headache (4/11), chills (2/11) | Raised CRP (6/11), raised Trop T (9/9), raised Trop I (2/2), raised Pro-BNP (3/7) | Sinus tachycardia (2/11), ST elevation (8/11), T inversion (1/11), PR depression (2/11), ST depression (1/11)/reduced EF (1/2), normal ECHO (1/2) | Myocardial oedema (4/9), LGE+ (8/9), no biopsy done | NSAIDs (11/11), colchicine (4/11), steroids (4/11), beta-blockers (3/11), ACEi/ARB (2/11), IVIg (4/11) | Hospitalized and discharged (11/11) |
| 73 | Walters et al.83 | n = 1/29 years | Pfizer/second dose | Chest pain, nausea | Raised Trop T | Sinus bradycardia, ST elevation/normal ECHO | MRI—not reported, no biopsy done | NSAIDs, colchicine, antiplatelet | Hospitalized and discharged |
| 74 | Hasnie et al.84 | n = 1/22 years | Moderna/first dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | LGE+, no biopsy done | NSAIDs, colchicine, antiplatelet, beta-blocker | Hospitalized and discharged |
| 75 | Khogali and Abdelrahman85 | n = 1/29 years | Moderna/second dose | Fever, nausea, vomiting, diarrhoea, myalgia | Raised D-dimer, raised Trop T, raised Pro-BNP | ST elevation, nonspecific ST-T waves, short PR interval/pericardial effusion, reduced EF | MRI—not done, no biopsy done | NSAIDs, colchicine, steroid, antiplatelet, inotrope | Hospitalized and discharged |
| 76 | Di Tano et al.86 | n = 1/29 years | Moderna/first dose | Fever, chest pain | Raised CRP, raised Trop T | ST elevation/ECHO—not reported | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine | Hospitalized and discharged |
| 77 | Maki et al.87 | n = 1/20 years | Moderna/second dose | Dyspnoea, fever, chest pain | Raised Trop I | Sinus tachycardia, ST elevation/pericardial effusion, reduced EF | LGE+, Biopsy—lymphocytic infiltration in myocardium | Diuretics, beta-blockers, inotrope, ACEi/ARB | Hospitalized and discharged |
| 78 | Ammirati et al.88 | n = 1/56 years | Pfizer/second dose | Chest pain | Raised D-dimer, raised CPK-MB, raised Trop T | ST elevation, peak T waves/ECHO—not reported | Myocardial oedema, LGE+, no biopsy done | NSAIDs, colchicine | Hospitalized and discharged |
| 79 | Rodriguez et al.89 | n = 1/68 years | AstraZeneca/first dose | Chest pain, sweating | Thrombocytopenia, raised CRP, raised Trop T | Atrial fibrillation/reduced EF | MRI—not reported, no biopsy done | Parenteral anticoagulant, inotrope | Hospitalized and discharged |
| 80 | Chen et al.90 | n = 1/16 years | Pfizer/first dose | Fever, chest pain, myalgia | Raised Trop T | ST elevation, PR depression/reduced EF | Myocardial oedema, LGE+, no biopsy done | NSAIDs, beta-blocker, ACEi/ARB | Hospitalized and discharged |
| 81 | Hudson et al.91 | n = 2/22–24 years | Pfizer (2/2)/second dose (2/2) | Fever (2/2), chest pain (1/2), nausea (1/2), vomiting (1/2), myalgia (1/2), chills (2/2), substernal pain (1/2), diaphoresis (1/2) | Raised CRP (2/2), raised D-dimer (1/2), raised Trop T (2/2) | J point elevation (1/2), wide QRS complexes (1/2)/reduced EF (1/2) | MRI—nor reported, no biopsy done | NSAIDs (2/2), colchicine (2/2), antiplatelet (2/2) | Hospitalized and discharged (2/2) |
| 82 | Visclosky et al.92 | n = 1/15 years | Pfizer/second dose | Fever, chest pain, headache | Raised Trop T | ST elevation/reduced EF | MRI—not reported, no biopsy done | NSAIDs | Hospitalized and discharged |
| 83 | Dionne et al.93 | n = 15/29 years | Pfizer/first dose (1/15), second dose (14/15) | Fever (10/15), chest pain (15/15), palpitation (1/15), nausea (1/15), vomiting (1/15), myalgia (9/15), headache (6/15) | Raised CRP (8/14), raised Trop T (15/15) | ST elevation (9/15), T inversion (2/15), nonspecific ST-T changes (2/15), NSVT (1/15), PAC (1/15)/reduced EF (3/15) | Myocardial oedema (2/15), LGE+ (12/15), no biopsy done | Steroids (7/7), IVIg (7/7) | Hospitalized and discharged (15/15) |
| 84 | Oster et al.94 | n = 1626/21 years | Pfizer (490/1626) Moderna (1136/1626) first dose (273/1626); second dose (1265/1626); dose NA:(88/1626) | Dyspnoea (242/1626), palpitation (65/1626), chest pain (727/1626) | Raised Trop T/I (792/809) | ECG (569/794) Normal echo (598/721) LVEF normal (637/721) | Cardiac MRI (223/312), LGE: 223; oedema: 223, no biopsy done | Rx Received by 676/1626, NSAIDS (589/676), intravenous anticoagulant (54/676), steroids (81/676), diuretics (11/676), IVIg (78/676), antiarrhythmics (18/676), O2 (12/676), inotrope (12/676) | Hospitalized (784/813) |
| 85 | Truong et al.95 | n = 139/15.8 years | Pfizer: (131/139); Moderna: (5/139); J&J: (1/139); NR: (2/139); Dose 1: (12/139) Dose 2: (128/139) | Dyspnoea (38/139), fever (43/139), palpitation (7/139), chest pain (138/139), vomiting (17/139), diarrhoea (3/139), myalgia/fatigue (26/139), joint pain (22/139), rash (5/139) | Raised Trop T/I (139/139), raised BNP (101/139), raised NT pro BNP (8/139) |
|
| Rx by 139, NSAIDS (113/139), Colchicine (11/139), steroids (30/139), IVIg (30/139), Biologics given to 1 (Anakinra), 2 patients got inotropes. | Hospitalized and discharged (139/139). Hospital stay 2 days average and 26 were admitted to the ICU. Myocarditis was definite in 49 and probable in 91 |
ACEi, angiotensin-converting enzyme inhibitor; ALT, alanine transaminase; ARB, angiotensin II receptor blocker; AST, aspartate transaminase; BNP, B-type natriuretic peptide; CHB, complete heart block; CRP, C-reactive protein; EF, ejection fraction; ESR, erythrocyte sedimentation rate; ICU, intensive care unit; IL-6, interleukin-6; IvIg, intravenous immunoglobulin; LDH, lactate dehydrogenase; LGE, late gadolinium enhancement; NSAID, non steroidal anti-inflammatory drugs; NT Pro-BNP, N terminal Pro BNP; PAC, premature atrial contractions; Trop, troponin; VPC, ventricular premature complexes.
Demographic features and clinical characteristics
Of the 2184 cases included, a majority of them were males (73.4%) with a mean age of 25.5 ± 14.2 years. Most of the patients (63.1%) belonged to the age group 0–20 years reflecting a high prevalence of vaccine induced myocarditis among young adults. Data regarding the race/ethnicity were available for 1688 (77.3%) individuals with subjects mostly belonging to the Caucasian (67.7%) and Hispanic (17.4%) ethnicity. The mean duration from vaccination to symptom onset was 4.01 ± 6.99 days. Chest pain (90.1%), dyspnoea (25.7%) and fever (11.9%) were the three most common presenting symptoms. Only a fraction (2.3%) of patients diagnosed with vaccine induced myocarditis had comorbidities such as hypertension (46%) and obesity (40%) as summarized in Table 2. Most of the patients with vaccine-induced myocarditis were recipient of the mRNA-based vaccines (99.4%), while it was rare in those who had received Janssen Ad26.CoV2. S (0.3%), AZD1222/ChAdOx1 (0.2%) and COVAXIN (0.04%).
Table 2.
Patient characteristics and laboratory parameters of myocarditis after SARS-CoV-2 vaccination
| Characteristics | Number of Patients (n = 2184) | n (%) |
|---|---|---|
| Age [Mean + SD] | Data available: n = 2170 | 25.5 ± 14.2 years |
| Age groups | Data available: n = 537 | |
| 0–20 years: | 339 (63.1%) | |
| 21–40 years: | 173 (32.2%) | |
| 41–60 years: | 14 (2.6%) | |
| 61–80 years: | 9 (1.7%) | |
| > 80 years: | 2 (0.4%) | |
| Gender | Data available: n = 2184 | Males: 1842 (91.2%) |
| Females: 342 (8.8%) | ||
| Ethnicity | Data available: n = 1688 | |
| Caucasian | 1143 (67.7%) | |
| Hispanic | 294 (17.4%) | |
| Latin | 0 (0%) | |
| Asian | 107 (6.3%) | |
| African | 74 (4.4%) | |
| Afro-American | 15 (0.9%) | |
| Other | 55 (3.2%) | |
| Clinical features | Data available: n = 1375 | |
| Fever | 164 (11.9%) | |
| Dyspnoea | 354 (25.7%) | |
| Cough | 5 (0.4%) | |
| Chest pain | 1239 (90.1%) | |
| Nausea | 43 (3.1%) | |
| Vomiting | 32 (2.3%) | |
| Diarrhoea | 8 (0.6%) | |
| Abdominal pain | 4 (0.3%) | |
| Palpitation | 84 (6.1%) | |
| Orthopnoea | 1 (0.07%) | |
| Syncope | 4 (0.3%) | |
| Peripheral oedema | 1 (0.07%) | |
| Myalgia | 138 (10.0%) | |
| Joint pain | 7 (0.5%) | |
| Headache | 79 (5.7%) | |
| Chills | 19 (1.4%) | |
| Numbness | 3 (0.2%) | |
| Rash | 5 (0.4%) | |
| Comorbidities | n = 50/419 (11.9%) | |
| Hypertension | 23 (46%) | |
| Diabetes | 6 (12%) | |
| Dyslipidaemia | 13 (26%) | |
| Overweight/obesity | 20 (40%) | |
| Coronary artery disease | 6 (12%) | |
| Asthma | 8 (16%) | |
| Malignancy | 2 (4%) | |
| Chronic kidney disease | 2 (4%) | |
| Prior myocarditis | 6 (12%) | |
| GERD | 2 (4%) | |
| Hospital stay | Data available: n = 1365 | 1331 (97.5%) |
| Duration of hospital stay [mean ± SD] | Data available: n = 487 | 4.3 ± 5.8 days |
| Time between vaccination and symptom onset [mean ± SD] | Data available: n = 2183 | 4.01 ± 6.99 days |
| Vaccine type | Data available: n = 2182 | Pfizer-BioNTech (BNT162b2): 1594 (73%) |
| mRNA-1273 (Moderna): 577 (26.4%) | ||
| Janssen Ad26.CoV2.S (J&J): 6 (0.3%) | ||
| AZD1222/ChAdOx1 (AstraZeneca): 4 (0.2%) | ||
| COVAXIN (Bharat Biotech): 1 (0.04%) | ||
| Vaccine dose | Data available: n = 2092a | First dose: 351b (16.8%) |
| Second dose: 1741 (83.2%) |
| Characteristics | Number of Patients (n = 2184) | n (%) |
|---|---|---|
| Age [Mean + SD] | Data available: n = 2170 | 25.5 ± 14.2 years |
| Age groups | Data available: n = 537 | |
| 0–20 years: | 339 (63.1%) | |
| 21–40 years: | 173 (32.2%) | |
| 41–60 years: | 14 (2.6%) | |
| 61–80 years: | 9 (1.7%) | |
| > 80 years: | 2 (0.4%) | |
| Gender | Data available: n = 2184 | Males: 1842 (91.2%) |
| Females: 342 (8.8%) | ||
| Ethnicity | Data available: n = 1688 | |
| Caucasian | 1143 (67.7%) | |
| Hispanic | 294 (17.4%) | |
| Latin | 0 (0%) | |
| Asian | 107 (6.3%) | |
| African | 74 (4.4%) | |
| Afro-American | 15 (0.9%) | |
| Other | 55 (3.2%) | |
| Clinical features | Data available: n = 1375 | |
| Fever | 164 (11.9%) | |
| Dyspnoea | 354 (25.7%) | |
| Cough | 5 (0.4%) | |
| Chest pain | 1239 (90.1%) | |
| Nausea | 43 (3.1%) | |
| Vomiting | 32 (2.3%) | |
| Diarrhoea | 8 (0.6%) | |
| Abdominal pain | 4 (0.3%) | |
| Palpitation | 84 (6.1%) | |
| Orthopnoea | 1 (0.07%) | |
| Syncope | 4 (0.3%) | |
| Peripheral oedema | 1 (0.07%) | |
| Myalgia | 138 (10.0%) | |
| Joint pain | 7 (0.5%) | |
| Headache | 79 (5.7%) | |
| Chills | 19 (1.4%) | |
| Numbness | 3 (0.2%) | |
| Rash | 5 (0.4%) | |
| Comorbidities | n = 50/419 (11.9%) | |
| Hypertension | 23 (46%) | |
| Diabetes | 6 (12%) | |
| Dyslipidaemia | 13 (26%) | |
| Overweight/obesity | 20 (40%) | |
| Coronary artery disease | 6 (12%) | |
| Asthma | 8 (16%) | |
| Malignancy | 2 (4%) | |
| Chronic kidney disease | 2 (4%) | |
| Prior myocarditis | 6 (12%) | |
| GERD | 2 (4%) | |
| Hospital stay | Data available: n = 1365 | 1331 (97.5%) |
| Duration of hospital stay [mean ± SD] | Data available: n = 487 | 4.3 ± 5.8 days |
| Time between vaccination and symptom onset [mean ± SD] | Data available: n = 2183 | 4.01 ± 6.99 days |
| Vaccine type | Data available: n = 2182 | Pfizer-BioNTech (BNT162b2): 1594 (73%) |
| mRNA-1273 (Moderna): 577 (26.4%) | ||
| Janssen Ad26.CoV2.S (J&J): 6 (0.3%) | ||
| AZD1222/ChAdOx1 (AstraZeneca): 4 (0.2%) | ||
| COVAXIN (Bharat Biotech): 1 (0.04%) | ||
| Vaccine dose | Data available: n = 2092a | First dose: 351b (16.8%) |
| Second dose: 1741 (83.2%) |
COVID-19, coronavirus disease 2019; GERD, gastro-oesophageal reflux diseases; RTPCR, reverse transcriptase polymerase chain reaction; SD, standard deviation.
a
Janssen Ad26.CoV2.S (J&J) administered as one dose, hence excluded.
b
One patient had myocarditis following both the doses of COVID-19 vaccine.
Table 2.
Patient characteristics and laboratory parameters of myocarditis after SARS-CoV-2 vaccination
| Characteristics | Number of Patients (n = 2184) | n (%) |
|---|---|---|
| Age [Mean + SD] | Data available: n = 2170 | 25.5 ± 14.2 years |
| Age groups | Data available: n = 537 | |
| 0–20 years: | 339 (63.1%) | |
| 21–40 years: | 173 (32.2%) | |
| 41–60 years: | 14 (2.6%) | |
| 61–80 years: | 9 (1.7%) | |
| > 80 years: | 2 (0.4%) | |
| Gender | Data available: n = 2184 | Males: 1842 (91.2%) |
| Females: 342 (8.8%) | ||
| Ethnicity | Data available: n = 1688 | |
| Caucasian | 1143 (67.7%) | |
| Hispanic | 294 (17.4%) | |
| Latin | 0 (0%) | |
| Asian | 107 (6.3%) | |
| African | 74 (4.4%) | |
| Afro-American | 15 (0.9%) | |
| Other | 55 (3.2%) | |
| Clinical features | Data available: n = 1375 | |
| Fever | 164 (11.9%) | |
| Dyspnoea | 354 (25.7%) | |
| Cough | 5 (0.4%) | |
| Chest pain | 1239 (90.1%) | |
| Nausea | 43 (3.1%) | |
| Vomiting | 32 (2.3%) | |
| Diarrhoea | 8 (0.6%) | |
| Abdominal pain | 4 (0.3%) | |
| Palpitation | 84 (6.1%) | |
| Orthopnoea | 1 (0.07%) | |
| Syncope | 4 (0.3%) | |
| Peripheral oedema | 1 (0.07%) | |
| Myalgia | 138 (10.0%) | |
| Joint pain | 7 (0.5%) | |
| Headache | 79 (5.7%) | |
| Chills | 19 (1.4%) | |
| Numbness | 3 (0.2%) | |
| Rash | 5 (0.4%) | |
| Comorbidities | n = 50/419 (11.9%) | |
| Hypertension | 23 (46%) | |
| Diabetes | 6 (12%) | |
| Dyslipidaemia | 13 (26%) | |
| Overweight/obesity | 20 (40%) | |
| Coronary artery disease | 6 (12%) | |
| Asthma | 8 (16%) | |
| Malignancy | 2 (4%) | |
| Chronic kidney disease | 2 (4%) | |
| Prior myocarditis | 6 (12%) | |
| GERD | 2 (4%) | |
| Hospital stay | Data available: n = 1365 | 1331 (97.5%) |
| Duration of hospital stay [mean ± SD] | Data available: n = 487 | 4.3 ± 5.8 days |
| Time between vaccination and symptom onset [mean ± SD] | Data available: n = 2183 | 4.01 ± 6.99 days |
| Vaccine type | Data available: n = 2182 | Pfizer-BioNTech (BNT162b2): 1594 (73%) |
| mRNA-1273 (Moderna): 577 (26.4%) | ||
| Janssen Ad26.CoV2.S (J&J): 6 (0.3%) | ||
| AZD1222/ChAdOx1 (AstraZeneca): 4 (0.2%) | ||
| COVAXIN (Bharat Biotech): 1 (0.04%) | ||
| Vaccine dose | Data available: n = 2092a | First dose: 351b (16.8%) |
| Second dose: 1741 (83.2%) |
| Characteristics | Number of Patients (n = 2184) | n (%) |
|---|---|---|
| Age [Mean + SD] | Data available: n = 2170 | 25.5 ± 14.2 years |
| Age groups | Data available: n = 537 | |
| 0–20 years: | 339 (63.1%) | |
| 21–40 years: | 173 (32.2%) | |
| 41–60 years: | 14 (2.6%) | |
| 61–80 years: | 9 (1.7%) | |
| > 80 years: | 2 (0.4%) | |
| Gender | Data available: n = 2184 | Males: 1842 (91.2%) |
| Females: 342 (8.8%) | ||
| Ethnicity | Data available: n = 1688 | |
| Caucasian | 1143 (67.7%) | |
| Hispanic | 294 (17.4%) | |
| Latin | 0 (0%) | |
| Asian | 107 (6.3%) | |
| African | 74 (4.4%) | |
| Afro-American | 15 (0.9%) | |
| Other | 55 (3.2%) | |
| Clinical features | Data available: n = 1375 | |
| Fever | 164 (11.9%) | |
| Dyspnoea | 354 (25.7%) | |
| Cough | 5 (0.4%) | |
| Chest pain | 1239 (90.1%) | |
| Nausea | 43 (3.1%) | |
| Vomiting | 32 (2.3%) | |
| Diarrhoea | 8 (0.6%) | |
| Abdominal pain | 4 (0.3%) | |
| Palpitation | 84 (6.1%) | |
| Orthopnoea | 1 (0.07%) | |
| Syncope | 4 (0.3%) | |
| Peripheral oedema | 1 (0.07%) | |
| Myalgia | 138 (10.0%) | |
| Joint pain | 7 (0.5%) | |
| Headache | 79 (5.7%) | |
| Chills | 19 (1.4%) | |
| Numbness | 3 (0.2%) | |
| Rash | 5 (0.4%) | |
| Comorbidities | n = 50/419 (11.9%) | |
| Hypertension | 23 (46%) | |
| Diabetes | 6 (12%) | |
| Dyslipidaemia | 13 (26%) | |
| Overweight/obesity | 20 (40%) | |
| Coronary artery disease | 6 (12%) | |
| Asthma | 8 (16%) | |
| Malignancy | 2 (4%) | |
| Chronic kidney disease | 2 (4%) | |
| Prior myocarditis | 6 (12%) | |
| GERD | 2 (4%) | |
| Hospital stay | Data available: n = 1365 | 1331 (97.5%) |
| Duration of hospital stay [mean ± SD] | Data available: n = 487 | 4.3 ± 5.8 days |
| Time between vaccination and symptom onset [mean ± SD] | Data available: n = 2183 | 4.01 ± 6.99 days |
| Vaccine type | Data available: n = 2182 | Pfizer-BioNTech (BNT162b2): 1594 (73%) |
| mRNA-1273 (Moderna): 577 (26.4%) | ||
| Janssen Ad26.CoV2.S (J&J): 6 (0.3%) | ||
| AZD1222/ChAdOx1 (AstraZeneca): 4 (0.2%) | ||
| COVAXIN (Bharat Biotech): 1 (0.04%) | ||
| Vaccine dose | Data available: n = 2092a | First dose: 351b (16.8%) |
| Second dose: 1741 (83.2%) |
COVID-19, coronavirus disease 2019; GERD, gastro-oesophageal reflux diseases; RTPCR, reverse transcriptase polymerase chain reaction; SD, standard deviation.
a
Janssen Ad26.CoV2.S (J&J) administered as one dose, hence excluded.
b
One patient had myocarditis following both the doses of COVID-19 vaccine.
Laboratory, ECG and radiological investigations
The details of various laboratory and radiological investigations have been summarized in Table 3. Inflammatory markers such as CRP was elevated in 325/390 (83.3%) patients. An elevated cardiac troponin T/troponin I was reported in 1330/1363 (97.6%) patients, while elevated Brain natriuretic peptide (BNP) and N terminal pro BNP were observed in 24.5% and 65.6% patients each. An abnormal ECG was reported in 979/1313 (74.6%) patients with ST segment elevation in 342 (34.9%), T-wave inversion in 90 (9.2%), non-sustained ventricular tachycardia (VT) in 19 (1.9%), VT and ventricular fibrillation in 1 (0.1%) patient each. Complete heart block and atrial fibrillation were reported in 2 (0.2%) patients each. Echocardiographic data were available for 1243 patients (56.9%) of whom 288 (23.2%) had a reduced LVEF (LVEF < 55%), while 955 (76.8%) had normal LV systolic functions. Data regarding the severity of LV dysfunction was available in 119/288 (41.3%) patients with most of them [92 (77.3%)] having mild LV systolic dysfunction (LVEF: 41–55%) with severe LV dysfunction (LVEF < 30%) in only 15 (12.6%) patients. Right ventricular dysfunction was present in 8 (0.6%), while pericardial effusion was reported in 23 (1.8%). Data regarding Cardiovascular magnetic resonance imaging (CMR) were available for 670 patients of whom had 424 (63.3%) evidence of myocardial oedema, 541 (80.7%) had late gadolinium enhancement (LGE) and 28 (4.2%) had pericardial effusion. None of the patients had any evidence of coronary artery aneurysms/obstructive coronary artery disease on cardiac imaging. LGE had a predominant sub-epicardial distribution in 169 (86.2%) patients followed by mid-myocardial in 48 (24.5%) patients, subendocardial and transmural in 2 (1%) patients each.
Table 3.
Imaging findings in myocarditis after SARS-CoV-2 vaccination
| Investigations | Number of patients (n = 2184) | n (%) |
|---|---|---|
| Haematology: | ||
| Haemoglobin (g/dl) | Data available: 82 | 14.395 ± 2.352 |
| Total leucocyte count (per mm3) | Data available: 137 | 10 038.23 ± 4841.86 |
| Absolute lymphocyte count (per mm3) | Data available: 40 | 2044.10 ± 814.04 |
| Platelet count (per mm3) | Data available: 34 | 219 139.29 ± 156 160.25 |
| Thrombocytopenia | Data available: 34 | 5 (17.8%) |
| Organ functions: | ||
| Serum creatinine (mg/dl) | Data available: 73 | 1.06 ± 0.50 |
| Cardiac troponin T (ng/ml) | Data available: 389 | 7.96 ± 22.90 |
| Cardiac troponin I (ng/ml) | Data available: 124 | 11.51 ± 12.30 |
| Positive troponin T/I* | Data available: 1363 | 1330 (97.6%) |
| Serum CK-MB | Data available: 23 | 49.29 ± 49.78 |
| Serum BNP (pg/ml) | Data available: 154 | 1347.49 ± 6991.65 |
| Raised BNP (>100 pg/ml) | Data available: 53 | 13 (24.5%) |
| Serum NT-proBNP (pg/ml) | Data available: 40 | 10 914.61 ± 47 220.97 |
| Raised NT-proBNP (>300 pg/ml) | Data available: 32 | 21 (65.6%) |
| AST (U/L) | Data available: 24 | 63.22 ± 44.28 |
| ALT (U/L) | Data available: 24 | 36.52 ± 23.93 |
| Inflammatory markers: | ||
| LDH (U/l) | Data available: 12 | 382.92 ± 176.15 |
| CRP (mg/dl) | Data available: 411 | 7.89 ± 11.43 |
| Raised CRP (>3 mg/dl) | Data available: 390 | 325 (83.3%) |
| ESR (mm/h) | Data available: 113 | 19.78 ± 12.58 |
| Raised ESR (>30 mm/h) | Data available: 113 | 11 (9.7%) |
| D-Dimer (ng/ml) | Data available: 31 | 1558.33 ± 3938.55 |
| Imaging | ||
| Echocardiogram: | Data available: 1243 | |
| − Baseline EF (%) | 52.6 ± 9.9 | |
| − Normal LVEF (>55%) | Data available: 119 | 955 (76.8%) |
| − Mild LV dysfunction (LVEF: 40–54%) | 92 (77.3%) | |
| − Moderate LV dysfunction (LVEF: 30–39%) | 12 (10.1%) | |
| − Severe LV dysfunction (LVEF: <30%) | 15 (12.6%) | |
| − Right ventricular dysfunction | 8 (0.6%) | |
| − Pericardial effusion | 23 (1.8%) | |
| Cardiac MRI: | ||
| LGE | Data available: 670 | 541 (80.7%) |
| LGE distribution: | Data available: 196 | |
| • Sub-epicardial | 169 (86.2%) | |
| • Mid myocardial | 48 (24.5%) | |
| • Sub-endocardial | 2 (1%) | |
| • Transmural | 2 (1%) | |
| Myocardial oedema | Data available: 670 | 424 (63.3%) |
| Pericardial effusion | Data available: 670 | 28 (4.2%) |
| T1 values (mean ± SD) | Data available: 74 | 987.3 ± 351.6 ms |
| T2 values (mean ± SD) | Data available: 68 | 58.1 ± 8.7 ms |
| Investigations | Number of patients (n = 2184) | n (%) |
|---|---|---|
| Haematology: | ||
| Haemoglobin (g/dl) | Data available: 82 | 14.395 ± 2.352 |
| Total leucocyte count (per mm3) | Data available: 137 | 10 038.23 ± 4841.86 |
| Absolute lymphocyte count (per mm3) | Data available: 40 | 2044.10 ± 814.04 |
| Platelet count (per mm3) | Data available: 34 | 219 139.29 ± 156 160.25 |
| Thrombocytopenia | Data available: 34 | 5 (17.8%) |
| Organ functions: | ||
| Serum creatinine (mg/dl) | Data available: 73 | 1.06 ± 0.50 |
| Cardiac troponin T (ng/ml) | Data available: 389 | 7.96 ± 22.90 |
| Cardiac troponin I (ng/ml) | Data available: 124 | 11.51 ± 12.30 |
| Positive troponin T/I* | Data available: 1363 | 1330 (97.6%) |
| Serum CK-MB | Data available: 23 | 49.29 ± 49.78 |
| Serum BNP (pg/ml) | Data available: 154 | 1347.49 ± 6991.65 |
| Raised BNP (>100 pg/ml) | Data available: 53 | 13 (24.5%) |
| Serum NT-proBNP (pg/ml) | Data available: 40 | 10 914.61 ± 47 220.97 |
| Raised NT-proBNP (>300 pg/ml) | Data available: 32 | 21 (65.6%) |
| AST (U/L) | Data available: 24 | 63.22 ± 44.28 |
| ALT (U/L) | Data available: 24 | 36.52 ± 23.93 |
| Inflammatory markers: | ||
| LDH (U/l) | Data available: 12 | 382.92 ± 176.15 |
| CRP (mg/dl) | Data available: 411 | 7.89 ± 11.43 |
| Raised CRP (>3 mg/dl) | Data available: 390 | 325 (83.3%) |
| ESR (mm/h) | Data available: 113 | 19.78 ± 12.58 |
| Raised ESR (>30 mm/h) | Data available: 113 | 11 (9.7%) |
| D-Dimer (ng/ml) | Data available: 31 | 1558.33 ± 3938.55 |
| Imaging | ||
| Echocardiogram: | Data available: 1243 | |
| − Baseline EF (%) | 52.6 ± 9.9 | |
| − Normal LVEF (>55%) | Data available: 119 | 955 (76.8%) |
| − Mild LV dysfunction (LVEF: 40–54%) | 92 (77.3%) | |
| − Moderate LV dysfunction (LVEF: 30–39%) | 12 (10.1%) | |
| − Severe LV dysfunction (LVEF: <30%) | 15 (12.6%) | |
| − Right ventricular dysfunction | 8 (0.6%) | |
| − Pericardial effusion | 23 (1.8%) | |
| Cardiac MRI: | ||
| LGE | Data available: 670 | 541 (80.7%) |
| LGE distribution: | Data available: 196 | |
| • Sub-epicardial | 169 (86.2%) | |
| • Mid myocardial | 48 (24.5%) | |
| • Sub-endocardial | 2 (1%) | |
| • Transmural | 2 (1%) | |
| Myocardial oedema | Data available: 670 | 424 (63.3%) |
| Pericardial effusion | Data available: 670 | 28 (4.2%) |
| T1 values (mean ± SD) | Data available: 74 | 987.3 ± 351.6 ms |
| T2 values (mean ± SD) | Data available: 68 | 58.1 ± 8.7 ms |
ALT, alanine transaminase; AST, aspartate transaminase; BNP, B-terminal natriuretic peptide; CPK, creatine phosphokinase; CRP, C-reactive protein; CT, computed tomography; EF, ejection fraction; ESR, erythrocyte sedimentation rate; GGO, ground glass opacities; IL-6, interleukin-6; IvIg, intravenous immunoglobulin; LDH, lactate dehydrogenase; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; NT Pro-BNP, N terminal Pro BNP; Trop T, reference normal ≤0.014 ng/ml; Trop I, reference normal <0.04 ng/ml.
Table 3.
Imaging findings in myocarditis after SARS-CoV-2 vaccination
| Investigations | Number of patients (n = 2184) | n (%) |
|---|---|---|
| Haematology: | ||
| Haemoglobin (g/dl) | Data available: 82 | 14.395 ± 2.352 |
| Total leucocyte count (per mm3) | Data available: 137 | 10 038.23 ± 4841.86 |
| Absolute lymphocyte count (per mm3) | Data available: 40 | 2044.10 ± 814.04 |
| Platelet count (per mm3) | Data available: 34 | 219 139.29 ± 156 160.25 |
| Thrombocytopenia | Data available: 34 | 5 (17.8%) |
| Organ functions: | ||
| Serum creatinine (mg/dl) | Data available: 73 | 1.06 ± 0.50 |
| Cardiac troponin T (ng/ml) | Data available: 389 | 7.96 ± 22.90 |
| Cardiac troponin I (ng/ml) | Data available: 124 | 11.51 ± 12.30 |
| Positive troponin T/I* | Data available: 1363 | 1330 (97.6%) |
| Serum CK-MB | Data available: 23 | 49.29 ± 49.78 |
| Serum BNP (pg/ml) | Data available: 154 | 1347.49 ± 6991.65 |
| Raised BNP (>100 pg/ml) | Data available: 53 | 13 (24.5%) |
| Serum NT-proBNP (pg/ml) | Data available: 40 | 10 914.61 ± 47 220.97 |
| Raised NT-proBNP (>300 pg/ml) | Data available: 32 | 21 (65.6%) |
| AST (U/L) | Data available: 24 | 63.22 ± 44.28 |
| ALT (U/L) | Data available: 24 | 36.52 ± 23.93 |
| Inflammatory markers: | ||
| LDH (U/l) | Data available: 12 | 382.92 ± 176.15 |
| CRP (mg/dl) | Data available: 411 | 7.89 ± 11.43 |
| Raised CRP (>3 mg/dl) | Data available: 390 | 325 (83.3%) |
| ESR (mm/h) | Data available: 113 | 19.78 ± 12.58 |
| Raised ESR (>30 mm/h) | Data available: 113 | 11 (9.7%) |
| D-Dimer (ng/ml) | Data available: 31 | 1558.33 ± 3938.55 |
| Imaging | ||
| Echocardiogram: | Data available: 1243 | |
| − Baseline EF (%) | 52.6 ± 9.9 | |
| − Normal LVEF (>55%) | Data available: 119 | 955 (76.8%) |
| − Mild LV dysfunction (LVEF: 40–54%) | 92 (77.3%) | |
| − Moderate LV dysfunction (LVEF: 30–39%) | 12 (10.1%) | |
| − Severe LV dysfunction (LVEF: <30%) | 15 (12.6%) | |
| − Right ventricular dysfunction | 8 (0.6%) | |
| − Pericardial effusion | 23 (1.8%) | |
| Cardiac MRI: | ||
| LGE | Data available: 670 | 541 (80.7%) |
| LGE distribution: | Data available: 196 | |
| • Sub-epicardial | 169 (86.2%) | |
| • Mid myocardial | 48 (24.5%) | |
| • Sub-endocardial | 2 (1%) | |
| • Transmural | 2 (1%) | |
| Myocardial oedema | Data available: 670 | 424 (63.3%) |
| Pericardial effusion | Data available: 670 | 28 (4.2%) |
| T1 values (mean ± SD) | Data available: 74 | 987.3 ± 351.6 ms |
| T2 values (mean ± SD) | Data available: 68 | 58.1 ± 8.7 ms |
| Investigations | Number of patients (n = 2184) | n (%) |
|---|---|---|
| Haematology: | ||
| Haemoglobin (g/dl) | Data available: 82 | 14.395 ± 2.352 |
| Total leucocyte count (per mm3) | Data available: 137 | 10 038.23 ± 4841.86 |
| Absolute lymphocyte count (per mm3) | Data available: 40 | 2044.10 ± 814.04 |
| Platelet count (per mm3) | Data available: 34 | 219 139.29 ± 156 160.25 |
| Thrombocytopenia | Data available: 34 | 5 (17.8%) |
| Organ functions: | ||
| Serum creatinine (mg/dl) | Data available: 73 | 1.06 ± 0.50 |
| Cardiac troponin T (ng/ml) | Data available: 389 | 7.96 ± 22.90 |
| Cardiac troponin I (ng/ml) | Data available: 124 | 11.51 ± 12.30 |
| Positive troponin T/I* | Data available: 1363 | 1330 (97.6%) |
| Serum CK-MB | Data available: 23 | 49.29 ± 49.78 |
| Serum BNP (pg/ml) | Data available: 154 | 1347.49 ± 6991.65 |
| Raised BNP (>100 pg/ml) | Data available: 53 | 13 (24.5%) |
| Serum NT-proBNP (pg/ml) | Data available: 40 | 10 914.61 ± 47 220.97 |
| Raised NT-proBNP (>300 pg/ml) | Data available: 32 | 21 (65.6%) |
| AST (U/L) | Data available: 24 | 63.22 ± 44.28 |
| ALT (U/L) | Data available: 24 | 36.52 ± 23.93 |
| Inflammatory markers: | ||
| LDH (U/l) | Data available: 12 | 382.92 ± 176.15 |
| CRP (mg/dl) | Data available: 411 | 7.89 ± 11.43 |
| Raised CRP (>3 mg/dl) | Data available: 390 | 325 (83.3%) |
| ESR (mm/h) | Data available: 113 | 19.78 ± 12.58 |
| Raised ESR (>30 mm/h) | Data available: 113 | 11 (9.7%) |
| D-Dimer (ng/ml) | Data available: 31 | 1558.33 ± 3938.55 |
| Imaging | ||
| Echocardiogram: | Data available: 1243 | |
| − Baseline EF (%) | 52.6 ± 9.9 | |
| − Normal LVEF (>55%) | Data available: 119 | 955 (76.8%) |
| − Mild LV dysfunction (LVEF: 40–54%) | 92 (77.3%) | |
| − Moderate LV dysfunction (LVEF: 30–39%) | 12 (10.1%) | |
| − Severe LV dysfunction (LVEF: <30%) | 15 (12.6%) | |
| − Right ventricular dysfunction | 8 (0.6%) | |
| − Pericardial effusion | 23 (1.8%) | |
| Cardiac MRI: | ||
| LGE | Data available: 670 | 541 (80.7%) |
| LGE distribution: | Data available: 196 | |
| • Sub-epicardial | 169 (86.2%) | |
| • Mid myocardial | 48 (24.5%) | |
| • Sub-endocardial | 2 (1%) | |
| • Transmural | 2 (1%) | |
| Myocardial oedema | Data available: 670 | 424 (63.3%) |
| Pericardial effusion | Data available: 670 | 28 (4.2%) |
| T1 values (mean ± SD) | Data available: 74 | 987.3 ± 351.6 ms |
| T2 values (mean ± SD) | Data available: 68 | 58.1 ± 8.7 ms |
ALT, alanine transaminase; AST, aspartate transaminase; BNP, B-terminal natriuretic peptide; CPK, creatine phosphokinase; CRP, C-reactive protein; CT, computed tomography; EF, ejection fraction; ESR, erythrocyte sedimentation rate; GGO, ground glass opacities; IL-6, interleukin-6; IvIg, intravenous immunoglobulin; LDH, lactate dehydrogenase; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; NT Pro-BNP, N terminal Pro BNP; Trop T, reference normal ≤0.014 ng/ml; Trop I, reference normal <0.04 ng/ml.
Diagnosis of vaccine induced myocarditis
A diagnosis of definite myocarditis was established in 523 (39.1%), probable in 797 (59.5%) and possible myocarditis in 19 (1.4%). In the majority of cases, this was based on symptoms, raised cardiac biomarkers and cardiac imaging findings supportive of myocarditis. However, a subset of patients (11; 0.5%) underwent histopathological evaluation based on Endomyocardial biopsy (EMB) (8; 0.37%) or autopsy (3; 0.14%) specimens. Histopathological findings included lympho-histiocytic myocarditis in 8 (0.37%) while in three patients (0.14%), there was no evidence of inflammatory infiltrate. Additionally, oeosinophilic infiltrate was observed in four patients (0.18%), while none had any evidence of myocyte necrosis.
Treatment and outcomes
Eighty-three (7.1%) of the patients diagnosed with vaccine-induced myocarditis were admitted into the ICU. Shock was reported in 23 (1.9%) patients during the course of hospital stay mandating cardiovascular support in the form of inotropes in 23 (1.9%), intra-aortic balloon pump in 1 (0.08%) or ECMO in 3 (0.2%). Non-invasive ventilation support was reported in 3 (0.2%) and mechanical ventilation in 4 (0.3%) patients. Table 4 summarizes the information regarding the treatment administered and the outcomes. A variety of anti-inflammatory therapies were used for the treatment of vaccine-induced myocarditis including non-steroidal antiinflammatory drugs (NSAIDs) (891; 76.5%), steroids (164; 14.1%), colchicine (85; 7.3%), intravenous immunoglobulin (IVIg) (155; 13.3%) and biologics 3 (0.2%) such as Anakinra. Additional therapies included beta-blockers in 72 (6.2%), diuretics in 32 (2.7%), ACE inhibitors/angiotensin receptor blockers in 51 (4.4%), angiotensin receptor-neprilysin inhibitor in 3 (0.2%) patients. Concomitant antibiotic therapy was administered in 0.7% patients, while 5.7% of the subjects’ received anticoagulants. The mean duration of the hospital stay was 4.3 ± 5.8 days. Data regarding the outcomes were available for 1317 subjects of whom 6 (0.5%) died during the course of hospital stay, while 1311 (99.5%) were discharged from the hospital.
Table 4.
Treatment and outcome of myocarditis after SARS-CoV-2 vaccination
| Medications and outcome | Number of patients | n (%) |
|---|---|---|
| Medical treatment | Data available: 1164 | |
| NSAIDS | 891 (76.5%) | |
| Steroids | 164 (14.1%) | |
| Colchicine | 85 (7.3%) | |
| Biologics | 3 (0.2%) | |
| Tocilizumab | 0 (0%) | |
| Anakinra | 3 (0.2%) | |
| Rituximab | 0 (0%) | |
| IVIg | 155 (13.3%) | |
| Antibiotics | 8 (0.7%) | |
| Antiplatelets | 32 (2.7%) | |
| Anticoagulants | 66 (5.7%) | |
| Parenteral | 65 (5.6%) | |
| Oral | 1 (0.08%) | |
| ACE inhibitors/ARBs | 51 (4.4%) | |
| Beta-blockers | 72 (6.2%) | |
| ARNI | 3 (0.2%) | |
| SGLT-2i | 1 (0.08%) | |
| Diuretics | 32 (2.7%) | |
| Antiarrhythmic | 18 (1.5%) | |
| Shock | Data available: 1164 | 23 (1.9%) |
| Inotropes | Data available: 1164 | 23 (1.9%) |
| IABP | Data available: 1164 | 1 (0.08%) |
| ECMO | Data available: 1164 | 3 (0.2%) |
| Oxygen support | Data available: 1164 | 18 (1.5%) |
| NIV | Data available: 1164 | 3 (0.2%) |
| IMV | Data available: 1164 | 4 (0.3%) |
| ICU stay | Data available: 1164 | 83 (7.1%) |
| Outcome | Data available: 1317 | |
| Died | 6 (0.5%) | |
| Discharged | 1311 (99.5%) |
| Medications and outcome | Number of patients | n (%) |
|---|---|---|
| Medical treatment | Data available: 1164 | |
| NSAIDS | 891 (76.5%) | |
| Steroids | 164 (14.1%) | |
| Colchicine | 85 (7.3%) | |
| Biologics | 3 (0.2%) | |
| Tocilizumab | 0 (0%) | |
| Anakinra | 3 (0.2%) | |
| Rituximab | 0 (0%) | |
| IVIg | 155 (13.3%) | |
| Antibiotics | 8 (0.7%) | |
| Antiplatelets | 32 (2.7%) | |
| Anticoagulants | 66 (5.7%) | |
| Parenteral | 65 (5.6%) | |
| Oral | 1 (0.08%) | |
| ACE inhibitors/ARBs | 51 (4.4%) | |
| Beta-blockers | 72 (6.2%) | |
| ARNI | 3 (0.2%) | |
| SGLT-2i | 1 (0.08%) | |
| Diuretics | 32 (2.7%) | |
| Antiarrhythmic | 18 (1.5%) | |
| Shock | Data available: 1164 | 23 (1.9%) |
| Inotropes | Data available: 1164 | 23 (1.9%) |
| IABP | Data available: 1164 | 1 (0.08%) |
| ECMO | Data available: 1164 | 3 (0.2%) |
| Oxygen support | Data available: 1164 | 18 (1.5%) |
| NIV | Data available: 1164 | 3 (0.2%) |
| IMV | Data available: 1164 | 4 (0.3%) |
| ICU stay | Data available: 1164 | 83 (7.1%) |
| Outcome | Data available: 1317 | |
| Died | 6 (0.5%) | |
| Discharged | 1311 (99.5%) |
ARB, angiotensin receptor blockers; ARNI, angiotensin receptor-neprilysin inhibitor; ECMO, extracorporeal membrane oxygenation; IABP, intra aortic balloon pump; ICU, intensive care unit; IMV, invasive mechanical ventilation; IVIg, intravenous immunoglobulin; MIS, multisystem inflammatory syndrome; NIV, non-invasive ventilation; NSAIDs, non steroidal antiinflammatory drugs; SGLT, sodium-glucose cotransporter-2 inhibitors.
Table 4.
Treatment and outcome of myocarditis after SARS-CoV-2 vaccination
| Medications and outcome | Number of patients | n (%) |
|---|---|---|
| Medical treatment | Data available: 1164 | |
| NSAIDS | 891 (76.5%) | |
| Steroids | 164 (14.1%) | |
| Colchicine | 85 (7.3%) | |
| Biologics | 3 (0.2%) | |
| Tocilizumab | 0 (0%) | |
| Anakinra | 3 (0.2%) | |
| Rituximab | 0 (0%) | |
| IVIg | 155 (13.3%) | |
| Antibiotics | 8 (0.7%) | |
| Antiplatelets | 32 (2.7%) | |
| Anticoagulants | 66 (5.7%) | |
| Parenteral | 65 (5.6%) | |
| Oral | 1 (0.08%) | |
| ACE inhibitors/ARBs | 51 (4.4%) | |
| Beta-blockers | 72 (6.2%) | |
| ARNI | 3 (0.2%) | |
| SGLT-2i | 1 (0.08%) | |
| Diuretics | 32 (2.7%) | |
| Antiarrhythmic | 18 (1.5%) | |
| Shock | Data available: 1164 | 23 (1.9%) |
| Inotropes | Data available: 1164 | 23 (1.9%) |
| IABP | Data available: 1164 | 1 (0.08%) |
| ECMO | Data available: 1164 | 3 (0.2%) |
| Oxygen support | Data available: 1164 | 18 (1.5%) |
| NIV | Data available: 1164 | 3 (0.2%) |
| IMV | Data available: 1164 | 4 (0.3%) |
| ICU stay | Data available: 1164 | 83 (7.1%) |
| Outcome | Data available: 1317 | |
| Died | 6 (0.5%) | |
| Discharged | 1311 (99.5%) |
| Medications and outcome | Number of patients | n (%) |
|---|---|---|
| Medical treatment | Data available: 1164 | |
| NSAIDS | 891 (76.5%) | |
| Steroids | 164 (14.1%) | |
| Colchicine | 85 (7.3%) | |
| Biologics | 3 (0.2%) | |
| Tocilizumab | 0 (0%) | |
| Anakinra | 3 (0.2%) | |
| Rituximab | 0 (0%) | |
| IVIg | 155 (13.3%) | |
| Antibiotics | 8 (0.7%) | |
| Antiplatelets | 32 (2.7%) | |
| Anticoagulants | 66 (5.7%) | |
| Parenteral | 65 (5.6%) | |
| Oral | 1 (0.08%) | |
| ACE inhibitors/ARBs | 51 (4.4%) | |
| Beta-blockers | 72 (6.2%) | |
| ARNI | 3 (0.2%) | |
| SGLT-2i | 1 (0.08%) | |
| Diuretics | 32 (2.7%) | |
| Antiarrhythmic | 18 (1.5%) | |
| Shock | Data available: 1164 | 23 (1.9%) |
| Inotropes | Data available: 1164 | 23 (1.9%) |
| IABP | Data available: 1164 | 1 (0.08%) |
| ECMO | Data available: 1164 | 3 (0.2%) |
| Oxygen support | Data available: 1164 | 18 (1.5%) |
| NIV | Data available: 1164 | 3 (0.2%) |
| IMV | Data available: 1164 | 4 (0.3%) |
| ICU stay | Data available: 1164 | 83 (7.1%) |
| Outcome | Data available: 1317 | |
| Died | 6 (0.5%) | |
| Discharged | 1311 (99.5%) |
ARB, angiotensin receptor blockers; ARNI, angiotensin receptor-neprilysin inhibitor; ECMO, extracorporeal membrane oxygenation; IABP, intra aortic balloon pump; ICU, intensive care unit; IMV, invasive mechanical ventilation; IVIg, intravenous immunoglobulin; MIS, multisystem inflammatory syndrome; NIV, non-invasive ventilation; NSAIDs, non steroidal antiinflammatory drugs; SGLT, sodium-glucose cotransporter-2 inhibitors.
Discussion
This review describes the demographic profile, clinical features, diagnostics and therapeutics of the patients developing myocarditis post-COVID-19 vaccination. Our results indicated that post-COVID-19 vaccine myocarditis was more prevalent among young males with the majority of reported cases being below 20 years of age. The predilection for younger age could be due to stronger immune responses seen in this age group as compared to adults. Studies have reported that the levels of proinflammatory cytokines such as TNF-alpha and IFN-gamma often increase at puberty and decline thereon.96 Additionally, gender differences could be due to varying effects of sex hormones on the immune system. Testosterone has been shown to lead to a stronger cellular immune response mediated by Th1 cells while oestrogen has an inhibitory effect on the pro-inflammatory T cells.97 These are significant observations as vaccination drives are being launched across the globe to enhance coverage, especially among children and adolescents. Awareness of this possible complication amongst medical professionals and the vaccination beneficiaries is crucial for seeking early medical attention. The apparent predilection for Caucasian race noted in our review requires watchful consideration as vaccine coverage improves and data emerges from other parts of the globe. Another striking observation in our review was that myocarditis occurred more frequently following administration of mRNA vaccines (99.4%) especially after the second dose (83.2%). While it may be a reporting bias or possibly be due to the greater global coverage by mRNA vaccines, there is always a chance of pathophysiological links which needs to be explored. mRNA vaccines have a nucleoside-modified mRNA, which encodes the viral spike glycoprotein of SARS-CoV-2. This viral spike protein then incites an adaptive immune response to identify and thereby neutralize the future infections with the virus. mRNA molecules can itself be immunogenic and the nucleoside modification tends to lower the innate immunogenicity with less production of inflammatory cytokines.98 However, in individuals with certain genetic predispositions, the immune system might detect mRNA as an antigen leading to an inflammatory cascade with production of pro-inflammatory cytokines and development of myocarditis.99 Other probable mechanisms of hyperimmunity include molecular mimicry by antibodies to SARS-CoV-2 spike proteins which cross-react with myocardial contractile proteins such as α-myosin and the possible role of natural killer cells.100 These hypotheses are also supported by the fact that a majority of cases of COVID-19 vaccine-induced myocarditis occurred following administration of the second dose of the vaccine. However, further research dwelling into plausible mechanisms of myocardial injury is of paramount importance to understand the clinico-pathophysiology and tailoring the therapeutics.
A possibility of COVID-19 vaccine-induced myocarditis should be considered among individuals developing chest pain, dyspnoea or fever within 3–4 days following vaccination. A diagnosis is often established based on clinical presentation and supplemented by elevated levels of cardiac biomarkers and supportive cardiac imaging. EMB, despite being the gold standard, has been sparingly used for the diagnosis of vaccine-induced myocarditis due to its invasive nature for a condition of mild nature with a conservative treatment approach.101 In our review, EMB was performed in only 0.37% of patients with the majority of them having lympho-histiocytic infiltration in the myocardium. A diagnosis of vaccine-induced myocarditis can often be challenging in individuals with recent SARS-CoV-2 infection; hence, protocols for testing for recent COVID-19 infection to eliminate its confounding effect should be in place. Cardiac imaging using echocardiography and CMR plays an important role in assessment of cardiac functions and morphology in patients with myocarditis. CMR not only helps in establishing the diagnosis of myocarditis but also excludes confounding abnormalities. The diagnosis of myocarditis on CMR is often established based on the revised Lake Louise criteria.102 In our review, classical CMR findings of myocarditis viz. LGE and myocardial oedema were reported in 80.7% and 63.3% patients, respectively. A majority of patients had a sub-epicardial distribution of LGE, a feature consistent with that of myocarditis. A majority of patients were categorized as definite/probable myocarditis (98.6%), while possible myocarditis was reported in 1.4% patients.
The treatment of myocarditis following COVID-19 vaccination is highly variable, probably due to the absence of defined guidelines as well as regional preferences, varying severity and clinical presentation. Overall, the therapeutic approach for symptomatic patients includes the use of NSAIDs and/or colchicine. Corticosteroids, IVIg and immunomodulators such as TNF-alpha inhibitors are often reserved for severe cases. Findings from our review too suggested that NSAIDs were the most common treatment modality, followed by colchicine and steroids. An important grey zone in the treatment strategy is the determination of need for hospitalization or intensive care. Most of the cases of vaccine-induced myocarditis were mild in nature with only 7.1% of them requiring ICU stay. Findings of our review suggested that clinical outcomes of vaccine-associated myocarditis were mostly very favourable with mortality reported in 0.5% of subjects, while the rest of them had rapid spontaneous recovery. It is important to conclude that despite the alarming nature of this rare adverse event, it should not be a deterrent to mass vaccination as most of the patients had favourable outcomes with rapid recovery following therapy with oral anti-inflammatory agents and a short hospital stay. The risk–benefit ratio of vaccination unanimously favours the use of COVID-19 vaccines, which prevents severe forms of infection and reduces risk of hospitalization, ICU admissions and death in both young and elderly age groups.2 Large data registries and clinical cohorts are needed to strengthen diagnostic criteria, risk stratification and therapeutic approaches for vaccine-induced myocarditis. Till larger evidence emerges, the vaccine coverage should continue globally albeit the fear of myocarditis. However, prospective research should continue to systematically document this adverse event alongside, especially in the current scenario where boosters have entered the ball game, to strengthen our understanding of the precise nature of this condition.
Limitations
Our systematic review on COVID-19 vaccine-induced myocarditis had a few limitations. This study is mainly descriptive including primarily case reports and case series due to which the level of evidence is low. In addition, due to the inclusion of multiple studies, there is a risk of reporting bias. Vaccine inequity across the world and the availability of certain vaccines in different countries makes it difficult to evaluate and compare regional variations in the occurrence and severity of myocarditis.
Conclusion
Myocarditis following COVID-19 vaccination has the potential to spark fear and vaccine hesitancy. There is a need to understand that myocarditis following COVID-19 vaccination is often mild, more commonly diagnosed in young healthy adults after the second dose of mRNA vaccine, and is acute in onset followed by rapid recovery with conservative treatment. There is a need for prompt recognition of myocarditis to limit the hyperinflammatory response and prevent poor outcomes. The emergence of this adverse event calls for harmonizing case definitions for establishing a correct diagnosis as well as definite treatment guidelines. This would largely be possible through wider research, collaborative efforts and development of data registries and clinical cohorts.
Conflict of interest. None declared.
Author’s contributions
S.K., P.I. and D.M. involved in conceptualization, literature search, writing the original draft of the manuscript, literature search, planning, conduct and editing. Screening by title and abstract was conducted independently by two investigators (D.M. and M.G.). A third investigator (P.I.) was consulted to resolve differences of opinion in either phase. S.K., P.I., D.M., I.R. and M.G. involved in review and editing. Subsequent full-text review and data extraction was conducted by investigators (P.I., S.K., D.M., I.R. and M.G.) using Google Sheets (Google, Mountain View, CA, USA). All the authors have read and agreed with the submitted manuscript.
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