COVID-19 Science Update released: July 9, 2021 Edition 97

Two reports of myocarditis after 2 doses of either BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) highlight the importance of post-vaccination surveillance in identifying events too rare to be encountered even during Phase 3 clinical trials.

A. Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military.external icon Montgomery et al. JAMA Cardiology (June 29, 2021).

B. Patients with acute myocarditis following mRNA COVID-19 vaccinationexternal icon . Kim et al. JAMA Cardiology (June 29, 2021).

Key findings for Montgomery et al. and Kim et al.:

• The Military Health System identified 23 cases of acute myocarditis among >2.8 M vaccinees (Montgomery et al). At a tertiary care center in North Carolina (NC) that serves a population of >560,000 vaccinees, 4 cases were found (Kim et al).
• Both BNT162b2 and mRNA-1273 were represented among cases: in the military, 7 received BNT162b2 and 16, mRNA-1273; in NC, 2 received BNT162b2 and 2, mRNA-1273.
• All cases reported symptoms within 5 days after 2^nd dose. Ages: median 25 years (20-51) for the military and 23, 24, 36 and 70 years for NC.
• All presented with severe acute chest pain, had abnormal electrocardiogram results, and elevated troponin. Tests did not uncover alternative etiologies or underlying heart disease. All recovered uneventfully.

Methods: Adverse events identified through referrals within the military Defense Health System and review of Vaccine Adverse Events Reporting System (VAERS) reports were used to find cases for a retrospective review (Montgomery et al.). A database of cardiac magnetic imaging at a NC tertiary care center was searched for patients diagnosed with acute myocarditis between February-April in 2017-2021 with recent history of vaccination (Kim et al.). Combined Limitations: Lack of control groups precludes ability to establish causal relationship or estimate rates of myocarditis in vaccinated versus non-vaccinated populations.

Implications for both studies (Montgomery et al. and Kim et al.): As described in an editorialexternal icon , the mechanisms underlying these events are not yet known although are likely to be an immune mediated response to the mRNA SARS-CoV vaccines. Although surveillance is both informal and formal, including VAERS, Clinical Immunization Safety Assessment Project, V-safe, and reports to journals, editors of JAMA Cardiologyexternal icon suggest the system as a whole is invaluable.

PREPRINTS (NOT PEER-REVIEWED)

Ad26.COV2.S elicited neutralizing activity against Delta and other SARS-CoV-2 variants of concern.external icon Jongeneelen et al. bioRxiv (July 1, 2021).

Key findings:

• Compared to B.1, a single dose of Ad26.COV1.2 (Johnson & Johnson/Janssen) vaccine had reduced neutralization sensitivity to SARS-Cov-2 variants B.1.351 (3.6-fold less), P.1 (3.4-fold less), and B.1.617.2 (1.6-fold less).

Methods: Sera collected 71 days post vaccination with Ad26.COV2.Sfrom 8 participants in a phase 3 clinical trial (age range: 47-91) were tested for neutralizing activity against SARS-CoV-2 variants of concern including B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta). Limitations: Results from a clinical trial may not be representative of real-world vaccine effectiveness; small sample size.

Implications: In a small in-vitro study, Ad26.COV2.S vaccine neutralization was reduced against a variety of variants, though less so for B.1.617.2. Real world evidence will be necessary to evaluate the effectiveness of this vaccine against variant 1.617.2.

Figure:

Note: Adapted from Jongeneelen et al. Neutralization activity of serum antibodies elicited by Ad26.COV2.S vaccine against SARS-CoV-2 spike pseudotyped virus variants. Dots are independent measurements per virus variant with geometric mean titers as solid horizontal lines. Dotted line = limit of detection. Licensed under CC-BY-NC-ND 4.0.

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccinationexternal icon . Davis et al. medRxiv (June 28, 2021).

Key findings:

• Antibody titers produced by 2 doses of BNT162b2 (Pfizer/BioNTech) neutralized B.1.617.2, B.1.617.1, and B.1.351 variants 7.8-, 11.3-, and 9.6-fold less effectively than wild-type SARS-CoV-2 (Figure A).
  • Differences in neutralization against variants produced by ChAdOx1 (Oxford/AstraZeneca) were not significant.
• Mean antibody titers against all Wuhan were significantly higher in individuals vaccinated with BNT162b2 than in those vaccinated with ChAdOx1 (Figure B).

Methods: Post-vaccination BNT162b2 or ChAdOx1 sera from 155 healthy individuals (≥18 years old) in the UK COVID-19 Deployed Vaccine Cohort Study (DOVE) were tested for neutralizing antibody production against SARS-CoV-2 spike protein-pseudotyped HIV for the indicated variants. Limitations: The average age of individuals vaccinated with ChAdOx1 was 15 years older than those vaccinated with BNT162b2, which could confound comparisons across the vaccine groups.

Implications: BNT162b2 and ChAdOx1 vaccines induced neutralizing antibodies may be less efficient at targeting the B.1.617.2 variant compared to wild-type SARS-CoV-2.

Figure:

Note: Adapted from Davis et al. Neutralizing antibody titers produced by individuals vaccinated with 1 dose of BNT162b2 (n = 37), 2 doses of BNT162b2 (n = 50), 1 dose of ChAdOx1 (n = 50), and 2 doses of ChAdOx1 (n=18) against Wuhan (wild-type) compared to 3 variants (B.1.617.1, B.1.617.2, or B.1.351) (Top row), and comparisons between ChAdOx1 and BNT162b2 by dose for each variant (bottom row). Violin plot indicates median and quartiles; horizontal bars at top indicate significant differences. Licensed under CC-BY-ND 4.0.

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