Clinician Update—COVID-19

Myocarditis-Pericarditis following Vaccination

Additional or Booster Doses of Vaccine

June 25, 2021

Actions Requested

• Be aware of the association of rare cases of myocarditis and/or pericarditis with mRNA COVID-19 vaccination, particularly in adolescent and young adult males.
• Include counseling about this rare event to patients presenting for COVID-19 vaccination, including:
  1. the continued recommendation for mRNA vaccination in all age and gender groups from the Centers for Disease Control & Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP), 
  2. the still overwhelmingly favorable benefit-risk profile favoring vaccination, and
  3. the importance of seeking prompt evaluation if symptoms suggestive of myocarditis or pericarditis occur.
• Conduct a thorough evaluation in suspected cases of vaccine-associated cases and report them to CDC’s Vaccine Adverse Event Reporting System (VAERS).
• Be aware that at the current time no data or circumstances exist supporting a recommendation for additional or booster doses of COVID-19 vaccines.  

Myocarditis-Pericarditis

• CDC’s ACIP met on June 23 to review data from multi-modal vaccine safety surveillance systems addressing myocarditis-pericarditis and to consider an updated risk-benefit analysis with respect to mRNA COVID-19 vaccines.
• The findings did suggest that the association is likely causal, rare, typically mild, and does not substantially alter the benefit-risk analysis strongly favoring vaccination despite the real but low risk of myocarditis-pericarditis.  
• The Committee discussed options for deferring versus administering dose 2 among vaccinees who develop myocarditis-pericarditis and recover after dose 1, as well as offering dose 1 to candidates with a history of resolved myocarditis-pericarditis. However, a formal conclusion on this was not reached during the meeting.   
• The Committee discussed adding information about myocarditis-pericarditis to pre-vaccination counseling and patient materials.  
• CDC will continue surveillance and monitoring in order to update its risk-benefit analyses and vaccine recommendations going forward.
• Key findings reported:
  1. Myocarditis (rather than pericarditis) was the predominant diagnosis, although either or both can occur.
  2. Chest pain and dyspnea were the most common presenting symptoms.
  3. Diffuse ST-T wave changes on electrocardiography and/or elevated troponin were found in about 25% of VAERS-reported cases. Abnormal echocardiography or cardiac magnetic resonance imaging was reported in about 20% of VAERS-reported cases.  The proportion of cases undergoing such testing, however, was not specified. So, these figures underestimate the true proportion of cases with such findings.
  4. Most patients were hospitalized initially, but the median length of stay was just 1 day, and most patients had recovered clinically by the time their cases were reviewed.  Prolonged hospitalization or need for intensive care was extremely rare.   
  5. About ¾ of the cases occurred following the second dose.  Median time to onset after vaccination was 3-4 days with few cases having an onset greater than 7 days.  
  6. Median age was 30 years in cases following the first dose and 24 years following the second dose.  Cases over age 40 were extremely rare but did occur.  
  7. Peak risk was in males aged 12-24 years, with roughly 10-50 events per million 2^nd doses administered depending on the surveillance source and age of vaccinees. The risk in males appears to be 5-10 times higher than in females at all ages.  
  8. Both Pfizer and Moderna mRNA products were involved.   Janssen’s (Johnson-&-Johnson) vaccine was not involved.
  9. Accounting for deaths and hospitalizations prevented by vaccination, benefit-risk analysis strongly favored vaccination.  Other benefits not accounted for in the analysis included prevention of post-COVID conditions (e.g., multi-system inflammatory syndrome and “long” COVID), suppression of further emergence of variants, and equity impacts related to higher hospitalization and death rates in some groups in the absence of vaccination. 
• Typical elements of evaluation and management for suspected myocarditis in association with COVID-19 vaccination (consider consulting with a cardiologist):
  1. Testing: electrocardiogram, troponin, C-reactive protein, erythrocyte sedimentation rate, echocardiogram-and/or-cardiac MR, SARS-CoV-2 PCR, SARS-CoV-2 serology (ideally including anti-nucleocapsid antibody assay to differentiate from vaccine-acquired anti-S antibodies), respiratory viral panel
  2. Treatment: rest, non-steroidal anti-inflammatory drugs, colchicine
  3. For follow-up of patients with myocarditis, consult the recommendations from the American Heart Association and the American College of Cardiology.

Additional or Booster Doses

• The Committee expressed that no data or circumstances exist at the current time to support deliberating a recommendation for an additional or booster dose of COVID-19 vaccine.  The Committee expressed a relatively high tolerance for waiting for such data or circumstances to emerge prior to doing so.
• Currently, there is no evidence for declining clinical vaccine effectiveness with time and, although much attention is focused on antibody levels, no laboratory correlate of clinical immunity has been confirmed.   Even if antibody levels are a true correlate, the titer below which infection or disease becomes more likely has not been identified.  Furthermore, non-antibody wings of the immune response (e.g., protection via cell mediated immunity, memory T-and-B cells, etc.) may dominate over antibody levels and their course over time may be more durable than antibody levels.
• No authorized product exists at this time for a booster dose.  Prior to availability of such, if additional doses were recommended, they would either be an additional dose of a homologous or heterologous product that is authorized or approved by the FDA for use in the United States.
• Many members expressed concern about the booster issue distracting from the higher priority of achieving better coverage with the existing vaccines, both nationally and globally.   
• Key triggers for moving in the direction of a booster might include evidence of substantially reduced vaccine efficacy in one or more groups over time or emergence of a variant that escapes vaccine-acquired immunity.
• Groups highlighted for monitoring of vaccine effectiveness and consideration of additional or booster doses if such a time comes might include the following: severely immunosuppressed individuals, long-term care residents, other older adults, and/or healthcare workers.  
• The Committee expressed that further consideration of this matter should be based upon monitoring of ongoing results from initial phase 1-3 vaccine trials, heterologous and new product booster trials, breakthrough case investigations, variant surveillance, and vaccine effectiveness in priority groups.

Additional Resources

• ACIP Presentation Slides, June 23-25, 2021 (see key benefit-risk images on next page)

• Clinical Considerations: Myocarditis and Pericarditis after Receipt of mRNA COVID-19 Vaccines Among Adolescents and Young Adults

• Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination
  

Source: CDC ACIP, June 23, 2021