Myocarditis and pericarditis after Version 3.3. mRNA COVID-19 vaccination in August 6th 2021 children: Interim guidance 1 | Myocarditis and Pericarditis after mRNA COVID-19 vaccination in children – V3.3. Aug 6th, 2021 Summary statements for clinicians 1. How should cases be identified? - Any patient who presents with acute chest pain, palpitations, dyspnea, syncope or diaphoresis within 42 days after receiving a COVID-19 mRNA vaccine should be evaluated in-person for the possibility of myocarditis or pericarditis. - Patients with pericarditis usually have an abnormal ECG, and normal to mildly elevated troponins. Patients with myopericarditis may have an abnormal ECG result and have significantly elevated troponins with normal left ventricular function on the echocardiogram. Patients with myocarditis typically have an abnormal ECG, elevated troponins, and decreased left ventricular function on the echocardiogram. 2. What are the recommended investigations? - An ECG and troponin level should be performed in any patient with a suspicion of myocarditis or pericarditis following COVID-19 vaccination. For patients who present with fever, a CBC with differential, CRP, blood culture, sodium and albumin levels should also be performed. - Patients with a normal ECG and normal troponin levels do not need any further investigation. - Patients with an abnormal ECG and/or elevated troponin levels who are otherwise stable should have an echocardiogram performed within 48h. Patients who are hemodynamically unstable should have an echocardiogram performed urgently. 3. What is the management? - Most cases are self-limited and respond to nonsteroidal anti-inflammatory agents (NSAIDs). In some cases, colchicine may be considered on a case-by-case basis in discussion with cardiology. - Corticosteroid use should be avoided. 4. Which patients should be seen by a cardiologist? Which patients need to be transferred to SickKids? - Patients with a normal ECG and normal troponin levels do not need to be referred to a cardiologist. - Patients with an abnormal ECG and/or elevated troponin levels should be referred to a cardiologist for an echocardiogram. This can be performed as an outpatient in a community setting within 48h if the patient is well clinically. - In settings in which an echocardiogram or a cardiologist are not readily available, patients may be referred to the cardiology clinic at SickKids (or their local paediatric centre). - Any child with cardiac dysfunction or more than a small pericardial effusion seen by echocardiography should be discussed with cardiology at SickKids (or their local paediatric centre) to determine timing and location of cardiology assessment. - Any child with hemodynamic instability should be discussed with SickKids (or their local paediatric centre) via Criticall as per standard practice. 5. Which patients should be reported to Public Health as an Adverse Events Following Immunization? - Any patient with confirmed myocarditis or pericarditis following COVID-19 vaccination should be reported to Public Health as an Adverse Event Following Immunization (AEFI). - Patients who present with symptoms of myocarditis or pericarditis but with normal ECG and normal troponins may also be reported on a case-by-case basis, as deemed appropriate by the treating physician. It should be noted that all cases reported as an AEFI to Public Health will undergo thorough review for causality assessment between vaccination and presenting symptoms. 6. What should be done with the second dose of the COVID-19 vaccine? - For now, the National Advisory Committee on Immunization (NACI) has recommended for the second dose of mRNA COVID-19 vaccination to be deferred in children who experience myocarditis or pericarditis following the first dose until more information is available. - Patients with confirmed myocarditis or pericarditis can also be referred to a Special Immunization Clinic (SickKids, McMaster Children's Hospital or Children’s Hospital of Eastern Ontario) for causality assessment and further guidance on future doses of COVID-19 vaccines. 2 | Myocarditis and Pericarditis after mRNA COVID-19 vaccination in children – V3.3. Aug 6th, 2021 Table of Contents Page 4 1. Introduction Page 4 2. Case definitions Page 6 Table 1: Usual characteristics of pericarditis, myopericarditis and myocarditis Page 5 3. Recommended investigations Page 7 4. Management Page 7 5. Follow-up Page 9 Algorithm for the management of patients with myocarditis or pericarditis after mRNA COVID-19 Vaccination Page 10 Supplementary information Page 10 Supplementary table 1: Summary of published case series on myocarditis / pericarditis following COVID-19 mRNA vaccination Page 11 Supplementary table 2: Pericarditis Brighton Collaboration case definition Page 13 Supplementary table 3: Myocarditis Brighton Collaboration case definition Page 15 Box 1: Expanded investigation to consider in the investigation of select cases of myocarditis / pericarditis Page 17 References 3 | Myocarditis and Pericarditis after mRNA COVID-19 vaccination in children – V3.3. Aug 6th, 2021 1. Introduction Since April 2021, there are increasing reports of cases of myocarditis and pericarditis after mRNA COVID-19 vaccination (Pfizer-BioNTech BNT162b2 vaccine and Moderna mRNA-1233 vaccine).1-5 In Canada, there have been a small number of these reports.6-8 The Public Health Agency of Canada (PHAC), Health Canada and Public Health Ontario (PHO) are closely monitoring these rare events, including those among youth. To date, PHO has received reports of a number of cases of myocarditis/pericarditis in the 12 to 17 age group in Ontario through the provincial surveillance of Adverse Event Following Immunization (AEFI).6 The Centers for Disease Control (CDC) in the United States have also reported an increased risk of myocarditis and pericarditis in the 7 days after receipt of dose 1 or dose 2 of an mRNA COVID-19 vaccine, particularly among younger males after dose 2.9 A summary table of published case series on myocarditis and pericarditis following COVID-19 mRNA vaccination can be found in the supplementary information (Table 1). Preventing the spread of COVID-19 remains extremely important, and in Canada, the National Advisory Committee on Immunization (NACI) continues to recommend COVID-19 vaccines continue for all eligible individuals, including youth.10 Other countries using mRNA vaccines in young adults and adolescents are also continuing to recommend their use but are following the emerging evidence on this topic very closely as further information is obtained.9 The benefits of the mRNA vaccines continue to outweigh their risks in the authorized populations, as there are clear benefits of mRNA vaccines in reducing deaths and hospitalizations due to COVID-19 infections. This document aims to provide interim guidance based on consensus opinion for clinicians who will be assessing pediatric patients who develop myocarditis or pericarditis after mRNA COVID-19 vaccination and should not replace best clinical judgment. This document will be revised as further information on this condition is gained. The management and clinical decision algorithm can be found at the end of this document. 2. Case definitions International and national reports of myocarditis/pericarditis following vaccination with COVID-19 mRNA vaccines have emerged.1,6,8 These reports indicate that: • Cases have been seen after the first dose of a COVID-19 mRNA vaccine, but are more commonly reported after the second dose • Symptom onset was typically within several days after vaccination, with most cases being reported within 7 days after vaccination • Cases were mainly adolescents and young adults • Cases were more often males compared to females • Cases experienced mild illness, responded well to conservative treatment and rest, and their symptoms improved quickly. Myocarditis and pericarditis involve inflammation of the myocardium or the pericardium, respectively, in response to an infection or some other trigger. Symptoms can include shortness of breath, chest pain, or the feeling of a rapid or abnormal heart rhythm. Myocarditis and pericarditis may overlap in clinical practice. Cases of pericarditis with an associated elevation of troponins, in the absence of reduced left ventricular function may be designated as myopericarditis. The clinical definition and classification for pericarditis, myopericarditis and myocarditis are detailed and represented in Table 1. Until further data is gathered and a definition for an Adverse Event of Special Interest for myocarditis/pericarditis following COVID-19 vaccination has been established, patients who develop pericarditis or myocarditis up to 42 days (6 weeks) after vaccination should follow this guidance and should 4 | Myocarditis and Pericarditis after mRNA COVID-19 vaccination in children – V3.3. Aug 6th, 2021 be reported to public health.11,12 It should be noted that the peak incidence occurs 1-3 days after vaccination and up to 7 days; cases beyond this are expected to be rare and other diagnoses should be considered. Pericarditis: The diagnosis of acute pericarditis can be made in the presence of at least two of the following four criteria, as described in the European Society of Cardiology and American College of Cardiology Guidelines for Pericardial Disease8: 1. Pericarditic chest pain (sudden in onset, retrosternal, and pleuritic exacerbated by inspiration) 2. Pericardial rub found at auscultation 3. ECG changes including widespread ST-segment elevation or PR depression (See