Table 2.
Overall and non-COVID-19 mortality in the RCTs of adenovirus-vector vaccines
| Vaccine group (deaths/N) | Placebo group (deaths/N) | Relative risk (95% CI) | |
|---|---|---|---|
| AstraZeneca vs. placebo US/Chile/Peru7a | |||
| Overall mortality | 7/21587 | 7/10792 | 0.50 (0.18–1.42) |
| COVID-19 mortality | 0/21587 | 2/10792 | 0.0 |
| Cardiovascular mortalityb | 0/21587 | 2/10792 | 0.0 |
| Other non-COVID-19 mortality | 3/21587 | 3/10792 | 0.50 (0.10–2.48) |
| Accidentsc | 4/21587 | 0/10792 | N/A |
| Non-accident, non-COVID-19 mortality | 3/21587 | 5/10792 | 0.30 (0.07–1.25) |
| AstraZeneca vs. placebo South-Africa8,9 | |||
| Overall mortality | 1/1011 | 3/1010 | 0.33 (0.03–3.20) |
| COVID-19 mortality | 0/1011 | 0/1010 | N/A |
| Cardiovascular mortality | 0/1011 | 0/1010 | N/A |
| Other non-COVID-19 mortality | 0/1011 | 0/1010 | N/A |
| Accidentsd | 1/1011 | 3/1010 | 0.33 (0.03–3.20) |
| Non-accident, non-COVID-19 mortality | 0/1011 | 0/1010 | N/A |
| AstraZeneca vs. control vaccine UK, Brazil10 | |||
| Overall mortality | 2/11218 | 3/10901 | 0.65 (0.11–3.88) |
| COVID-19 mortality | 0/11218 | 1/10901 | 0.0 |
| Cardiovascular mortality | 0/11218 | 0/10901 | N/A |
| Other non-COVID-19 mortality | 2/11218 | 1/10901 | 1.94 (0.18–21.43) |
| Accidentse | 0/11218 | 1/10901 | 0.0 |
| Non-accident, non-COVID-19 mortality | 2/11218 | 1/10901 | 1.94 (0.18–21.43) |
| Johnson&Johnson vs. placebo11 | |||
| Overall mortality | 3/21895 | 16/21888 | 0.19 (0.05–0.64) |
| COVID-19 mortality | 0/21895 | 5/21888 | 0.0 |
| Cardiovascular mortalityb | 0/21895 | 2/21888 | 0.0 |
| Other non-COVID-19 mortality | 3/21895 | 7/21888 | 0.43 (0.11–1.66) |
| Accidentsf | 0/21895 | 2/21888 | 0.0 |
| Non-accident, non-COVID-19 mortality | 3/21895 | 9/21888 | 0.33 (0.09–1.23) |
| Gam-COVID-Vac vs. placebo12 | |||
| Overall mortality | 3/16427 | 1/5435 | 0.99 (0.10–9.54) |
| COVID-19 mortality | 2/16427 | 0/5435 | N/A |
| Cardiovascular mortalityb | 0/16427 | 1/5435 | 0.0 |
| Other non-COVID-19 mortality | 0/16427 | 0/5435 | N/A |
| Accidentsg | 1/16427 | 0/5435 | N/A |
| Non-accident, non-COVID-19 mortality | 0/16427 | 1/5435 | 0.0 |
| Combinedh | |||
| Overall mortality | 16/72138 | 30/50026 | 0.37 (0.19–0.70) |
| COVID-19 mortality | 2/72138 | 8/50026 | 0.11 (0.02–0.87) |
| Cardiovascular mortality | 0/72138 | 5/50026 | 0.065 (0.01–0.41)i |
| Other non-COVID-19 mortality | 8/72138 | 11/50026 | 0.58 (0.23–1.45) |
| Accidents | 6/72138 | 6/50026 | 0.69 (0.19–2.58) |
| Non-accident, non-COVID-19 mortality | 8/72138 | 16/50026 | 0.38 (0.17–0.88) |
Notes: In the AstraZeneca paper, data from UK and Brazil trials, using meningitis vaccine in the control group, were published in a meta-analysis with data from a South Africa trial,8,9 which used placebo. The South African trial has also been reported separately. We maintained the division in placebo and control vaccine. The RCT of Ad5-nCoV13 vaccine did not present causes of death by randomization group.
A publication from this AstraZeneca RCT reports data until July 30, 2021.38 While this provided longer follow-up and more deaths, the unbiased comparison of vaccinated and controls was broken by unblinding and provision of non-study COVID-19 vaccines, resulting in severe skewing of the follow-up time in the safety population, with a median follow-up time to receipt of non-study COVID-19 vaccine of 228 days in the 21,587 participants in vaccinated group vs. 103 days in the 10,793 participants in the placebo group. Interestingly, during this period, there were 14 vs. 8 deaths. This corresponds to death rates of 0.28/100,000 person days at risk vs. 0.72/100,000 person days at risk giving a relative risk of 0.40 (0.17–0.94), supporting a strong beneficial effect of the AstraZeneca vaccine. However, due to the unblinding, this result has not been included in the present analysis.
Judged as cardiovascular deaths: from AstraZeneca: “cardiac arrest”; “hemorrhagic transformation stroke” + “ischemic stroke”. From Johnson&Johnson trial: “acute myocardial infarction”; “cardiac failure”. From Gam-COVID-Vac trial: “hemorrhage stroke”.
There were four deaths: overdose (2), accident, road traffic accident.
There were four deaths: gunshot, blunt force trauma to head, homicide, suicide.
There was one death: traumatic brain injury.
There were two deaths: overdose, suicide.
There was one death: fracture of thoracic vertebra.
Mantel-Haenszel estimate.
Due to 0 events among the vaccinated we used the Peto OR method for pooling trial results.