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. 2022 Dec 5;50(2):126–138. doi: 10.1136/jme-2022-108449

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		 Rate Risk Harms 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 1685 593.5
(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		 Rate Risk Harms per 1 million third doses Hospitalisations 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 22 45 751.6
(14/306)×106 		BNT162b2: 32.0 1429.7/1
(45 751.6/32.0)
mRNA-1273
18/16750
Table 3f, 4b		 1 in 9 107 784.4
(18/167)×106 		mRNA-1273: 23.3 4625.9/1
(107 784.4/23.3)
2× reactogenicity among SARS-CoV-2 recovered
BNT162b250 56 1 in 11 74 895.4
0.637*2*(14/306)×106+0.363*(14/306)×106 		BNT162b2: 32.0 2340.5/1
(74 895.4/32.0)
mRNA-127350 56 1 in 4.5 176 443.1
0.637*2*(18/167)×106+0.363*(18/167)×106 		mRNA-1273: 23.3 7572.7/1
(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/a BNT162b2: 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/a BNT162b2
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.