Table 1

Risk-benefit analysis of third mRNA vaccination: definitions and rates for serious adverse events (SAEs), grade ≥3 reactogenicity and myo/pericarditis in 18–29 year-olds by manufacturer

1A. Serious adverse events (SAE) and
risk-benefit analysis		RateRiskHarms per
1 million third doses		Hospitalisations prevented per 1 million third doses
Absolute risk reduction=(1/adj NNV)×106 		Risk-benefit ratio of
third-dose SAEs per
COVID-19 hospitalisation prevented
SAE
An adverse event that results in any of the following conditions: death, life threatening at the time of the event, inpatient hospitalisation or prolongation of existing hospitalisation; persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event, based on medical judgement.		BNT162b2
3/505519
Slide 26		1 in 1685593.5
(106/1685)		BNT162b219 47
1/(8738/0.28)×106=1/31 207×106=32.0
hospitalisations prevented per million third doses		18.5/1
593.5/32.0=18.5
(BNT162b2 SAE19/BNT162b2 hospitalisations prevented)
mRNA-1273
0/17150
Table 4b		Not calculable*Not calculable*mRNA-127319 47
1/(11 994/0.28)×106=1/42 836×106=23.3
hospitalisations prevented per million third doses		Not calculable*
1B. Grade ≥3 reactogenicity
and risk-benefit analysis		RateRiskHarms per 1 million third dosesHospitalisations prevented per 1 million third doses
(as above)		Risk-benefit ratio of
third-dose grade ≥3 reactogenicity per COVID-19 hospitalisation prevented
Grade ≥3 reactogenicity
Defined as local/systemic adverse events that prevent daily routine activity or require use of a pain reliever (grade 3) or require an emergency room visit or hospitalisation (grade 4).		BNT162b2
14/30650
Table 3f		1 in 2245 751.6
(14/306)×106 		BNT162b2: 32.01429.7/1
(45 751.6/32.0)
mRNA-1273
18/16750
Table 3f, 4b		1 in 9107 784.4
(18/167)×106 		mRNA-1273: 23.34625.9/1
(107 784.4/23.3)
2× reactogenicity among SARS-CoV-2 recovered
BNT162b250 56 1 in 1174 895.4
0.637*2*(14/306)×106+0.363*(14/306)×106 		BNT162b2: 32.02340.5/1
(74 895.4/32.0)
mRNA-127350 56 1 in 4.5176 443.1
0.637*2*(18/167)×106+0.363*(18/167)×106 		mRNA-1273: 23.37572.7/1
(176 443.1/23.3)
1C. Myo/pericarditis and
risk-benefit analysis		Harms per
1 million
third doses (males)		Harms per
1 million
third doses (females)		Hospitalisations prevented per 1 million third doses
(as above)		Risk-benefit ratio of
third-dose myo/pericarditis per
COVID-19 hospitalisations prevented
Myocarditis
Presence of ≥1 new or worsening‡:

  • Chest pain/pressure/discomfort

  • Dyspnoea/shortness of breath/pain with breathing

  • Palpitations

  • Syncope AND


≥1 new finding of:

  • Troponin above normal limit

  • Abnormal ECG, EKG or rhythm monitoring findings consistent with myocarditis

  • Abnormal cardiac function or wall motion abnormalities on ECHO

  • cMRI findings consistent with myocarditis AND

  • No other identifiable cause of symptoms


Pericarditis
Presence of ≥2 new or worsening:

  • Acute chest pain§

  • Pericardial rub on exam

  • New ST-elevation or PR-depression on EKG

  • New or worsening pericardial effusion on echocardiogram or MRI

 Ages 18–39 Ages 18–39 Males Females
BNT162b2
147/million53
(Sharff et al)		n/aBNT162b2: 32.0


mRNA-1273: 23.3		BNT162b2
4.6/1
(147.0/32.0)		n/a
Ages 18–29 Ages 18–29
BNT162b2 (VSD): 47.6/million52
Slide 23		BNT162b2 (VSD):
4.7/million52
Slide 23		BNT162b2
1.5/1
(47.6/32.0)		BNT162b2
0.2/1
(4.7/32.0)
mRNA-1273 (VSD): 70.3/million52
Slide 23		mRNA-1273 (VSD): 13.9/million52
Slide 23		mRNA-1273
3.0/1
(70.3/23.3)		mRNA-1273
0.6/1
(13.9/23.3)
Ages 18–24 Ages 18–24
BNT162b2
126.6/million54
(Friedensohn et al**)		n/aBNT162b2
3.9/1
(126.6/32.0)		n/a
Ages 16–17† Ages 16–17†
BNT162b2 (VSD):
200.3/million51
Slide 25		BNT162b2 (VSD):
44.0/million51
Slide 25		BNT162b2
6.3/1
(200.3/32.0)		BNT162b2
1.4/1
(44.0/32.0)

  • *Footnote (h) from GRADE Table 3e: Overall, 4/344 (1.2%) participants experienced five SAEs during a median follow-up of 5.7 months after booster dose (administered at least 6 months after a 50 μg (n=173) or 100 μg (n=171) two-dose primary series); the sponsor deemed these unrelated to mRNA-1273. Data on an equivalent primary series comparison group were not available at the time of the GRADE assessment.50

  • **Based on hospitalised cases only within 21 days of receipt of mRNA-1273.54

  • †COVID-19 hospitalisation risk for aged 16–17 years is lower than for those aged 18–29 years, thus the risk/benefit ratio provided is an underestimate.

  • ‡Criteria for probable case. Confirmed case requires symptoms plus histopathological evidence OR elevated troponin AND cMRI findings.

  • §Typically described as pain made worse by lying down, deep inspiration or cough and relieved by sitting up or leaning forward, although other types of chest pain may occur.

  • cMRI, cardiac MRI; GRADE, Grading of Recommendations, Assessment, Development, and Evaluation; NNV, number needed to vaccinate; VSD, Vaccine Safety Datalink.