Abstract
This comparative effectiveness research study examines the effectiveness of full vaccination with Ad26.COV2.S vs BNT162b2 against COVID-19–related hospitalization.
Introduction
Although the Ad26.COV2.S vaccine (Janssen) showed an efficacy of 85.4% against severe and critical COVID-19 in the pivotal trial,1 its effectiveness in the general population against COVID-19 hospitalization was estimated to be approximately 68%,2,3 compared with approximately 90% for mRNA vaccines.4 However, to date, the effectiveness of Ad26.COV2.S has not been compared with that of other COVID-19 vaccines. In France, the Ad26.COV2.S vaccine was used from April 24, 2021, in people aged 55 years or older, whereas the BNT162b2 mRNA vaccine (Pfizer-BioNTech) was the most widely administered (78% of first doses). As of the end of July 2021, 19 million people aged 55 years or older (84% of the population in that age group) were partially or fully vaccinated. In this comparative effectiveness research study, we compare the effectiveness of full vaccination with Ad26.COV2.S vs BNT162b2 against COVID-19–related hospitalization.
Methods
The research group has permanent regulatory access to the anonymized data from the French National Health Data System (French decree No. 2016-1871, French law articles Art. R. 1461-13/14, French data protection authority decision CNIL-2016-316). Thus, no informed consent or specific approval by an ethics committee was required. This report follows the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) reporting guideline for comparative effectiveness research.
On the basis of the French National Health Data System5 (see the eAppendix in the Supplement), we constructed a matched cohort of participants aged 55 years or older vaccinated with either Ad26.COV2.S or BNT162b2 between April 24, 2021, and July 31, 2021 (ie, 99 days). Participants of the 2 groups were individually matched according to age, sex, area of residence (100 areas) and date of full vaccination (first dose for Ad26.COV2.S, second dose for BNT162b2). Each participant was followed from the date of injection (day 0) or day 14 or day 28 (time of full effectiveness) until hospitalization for COVID-19 (outcome), death, or the end of follow-up on August 31, 2021, whichever occurred first.
The COVID-19 hospitalization rate was compared between the 2 groups using inverse probability of treatment weighted Cox models. Data were analyzed using SAS statistical software version 9.4 (SAS Institute).
Results
The cohort included 689 275 participants vaccinated with Ad26.COV2.S (94% of all individuals of this age category vaccinated with Ad26.COV2.S) and 689 275 participants vaccinated with BNT162b2. The mean (SD) age was 65.8 (9.0) years, and 341 490 participants in each group (49.5%) were women. The 2 groups were similar in terms of socioeconomic and health characteristics (Table 1). During a median (IQR) follow-up of 54 (22-74) days from day 28 after injection, 129 COVID-19–related hospitalizations occurred in participants vaccinated with Ad26.COV2.S, and 23 hospitalizations occurred in those vaccinated with BNT162b2. The risk of hospitalization for COVID-19 from day 28 after injection was 5.2 times higher in individuals vaccinated with Ad26.COV2.S compared with those vaccinated with BNT162b2 (adjusted hazard ratio, 5.2; 95% CI, 3.4-7.9) (Table 2). On the basis of these results and according to an effectiveness of BNT162b2 of 92% (95% CI, 90%-94%) estimated from the same data set,6 we obtained an absolute effectiveness of Ad26.COV2.S of 59% (95% CI, 33%-75%).
Table 1. Characteristics of the Study Population at the Index Date, by Vaccine Received.
| Baseline characteristics | Participants, No. (%) | Standardized difference | |
|---|---|---|---|
| Pfizer (n = 689 275) | Janssen (n = 689 275) | ||
| Age, mean (SD), y | 65.8 (9.0) | 65.8 (9.0) | 0.00 |
| Age range, y | |||
| 55-59 | 203 666 (29.5) | 203 666 (29.5) | 0.00 |
| 60-64 | 165 888 (24.1) | 165 888 (24.1) | |
| 65-69 | 129 310 (18.8) | 129 310 (18.8) | |
| 70-74 | 85 465 (12.4) | 85 465 (12.4) | |
| 75-79 | 38 676 (5.6) | 38 676 (5.6) | |
| 80-84 | 27 089 (3.9) | 27 089 (3.9) | |
| 85-89 | 22 894 (3.3) | 22 894 (3.3) | |
| ≥90 | 16 287 (2.4) | 16 287 (2.4) | |
| Sex | |||
| Female | 341 490 (49.5) | 341 490 (49.5) | 0.00 |
| Male | 347 785 (50.5) | 347 785 (50.5) | |
| Administrative regions | |||
| Auvergne-Rhône Alpes | 70 286 (10.2) | 70 286 (10.2) | 0.00 |
| Bourgogne Franche Comté | 31 072 (4.5) | 31 072 (4.5) | |
| Bretagne | 46 299 (6.7) | 46 299 (6.7) | |
| Centre-Val de Loire | 33 181 (4.8) | 33 181 (4.8) | |
| Corse | 1322 (0.2) | 1322 (0.2) | |
| Grand Est | 57 914 (8.4) | 57 914 (8.4) | |
| Guadeloupe | 121 (<0.1) | 121 (<0.1) | |
| Guyane | 29 (<0.1) | 29 (<0.1) | |
| Hauts de France | 67 759 (9.8) | 67 759 (9.8) | |
| Ile de France | 77 758 (11.3) | 77 758 (11.3) | |
| La Réunion | 9816 (1.4) | 9816 (1.4) | |
| Martinique | 602 (0.1) | 602 (0.1) | |
| Mayotte | 10 (<0.1) | 10 (<0.1) | |
| Normandie | 42 934 (6.2) | 42 934 (6.2) | |
| Nouvelle Aquitaine | 85 172 (12.4) | 85 172 (12.4) | |
| Occitanie | 68 557 (9.9) | 68 557 (9.9) | |
| Pays de Loire | 46 019 (6.7) | 46 019 (6.7) | |
| Provence Alpes Cote | 50 424 (7.3) | 50 424 (7.3) | |
| Index of deprivation (quintiles) | |||
| 1 (less deprived) | 111 954 (16.2) | 103 143 (15.0) | 0.05 |
| 2 | 130 654 (19.0) | 125 758 (18.2) | |
| 3 | 140 763 (20.4) | 141 421 (20.5) | |
| 4 | 149 910 (21.7) | 154 981 (22.5) | |
| 5 (more deprived) | 143 485 (20.8) | 151 430 (22.0) | |
| Unknown | 12 509 (1.8) | 12 542 (1.8) | |
| Influenza vaccination in 2018 or 2019 | |||
| No | 575 478 (83.5) | 595 934 (86.5) | −0.08 |
| Yes | 113 797 (16.5) | 93 341 (13.5) | |
| Frailty | |||
| No | 655 054 (95.0) | 647 004 (93.9) | 0.05 |
| Yes | 34 221 (5.0) | 42 271 (6.1) | |
| Addiction to alcohol | |||
| No | 678 987 (98.5) | 670 557 (97.3) | 0.09 |
| Yes | 10 288 (1.5) | 18 718 (2.7) | |
| Addiction to tobacco smoking | |||
| No | 652 205 (94.6) | 644 552 (93.5) | 0.05 |
| Yes | 37 070 (5.4) | 44 723 (6.5) | |
| Hypertension | |||
| No | 431 663 (62.6) | 434 557 (63.0) | −0.01 |
| Yes | 257 612 (37.4) | 254 718 (37.0) | |
| Diabetes | |||
| No | 611 466 (88.7) | 604 658 (87.7) | 0.03 |
| Yes | 77 809 (11.3) | 84 617 (12.3) | |
| Dyslipidemia | |||
| No | 539 301 (78.2) | 546 973 (79.4) | −0.03 |
| Yes | 149 974 (21.8) | 142 302 (20.6) | |
| Obesity | |||
| No | 678 705 (98.5) | 678 452 (98.4) | 0.00 |
| Yes | 10 570 (1.5) | 10 823 (1.6) | |
| Coronary diseases | |||
| No | 646 997 (93.9) | 651 528 (94.5) | −0.03 |
| Yes | 42 278 (6.1) | 37 747 (5.5) | |
| Heart failure | |||
| No | 677 681 (98.3) | 676 259 (98.1) | 0.02 |
| Yes | 11 594 (1.7) | 13 016 (1.9) | |
| Cardiac rhythm or conduction disturbances | |||
| No | 662 974 (96.2) | 664 891 (96.5) | −0.01 |
| Yes | 26 301 (3.8) | 24 384 (3.5) | |
| Valvular diseases | |||
| No | 678 088 (98.4) | 679 521 (98.6) | −0.02 |
| Yes | 11 187 (1.6) | 9754 (1.4) | |
| Obliterating arterial disease of the lower limb | |||
| No | 676 328 (98.1) | 674 289 (97.8) | 0.02 |
| Yes | 12 947 (1.9) | 14 986 (2.2) | |
| Stroke | |||
| No | 673 133 (97.7) | 673 422 (97.7) | 0.00 |
| Yes | 16 142 (2.3) | 15 853 (2.3) | |
| Pulmonary embolism | |||
| No | 686 537 (99.6) | 687 242 (99.7) | −0.02 |
| Yes | 2738 (0.4) | 2033 (0.3) | |
| Chronic respiratory diseases (excluding cystic fibrosis) | |||
| No | 643 123 (93.3) | 641 582 (93.1) | 0.01 |
| Yes | 46 152 (6.7) | 47 693 (6.9) | |
| Long-term dialysis | |||
| No | 688 913 (99.9) | 689 163 (100) | −0.02 |
| Yes | 362 (0.1) | 112 (<0.1) | |
| Kidney transplant | |||
| No | 688 626 (99.9) | 689 192 (100) | −0.04 |
| Yes | 649 (0.1) | 83 (<0.1) | |
| Liver diseases | |||
| No | 682 503 (99.0) | 681 875 (98.9) | 0.01 |
| Yes | 6772 (1.0) | 7400 (1.1) | |
| Active cancers | |||
| No | 667 567 (96.9) | 674 000 (97.8) | −0.06 |
| Yes | 21 708 (3.1) | 15 275 (2.2) | |
| Neurotic and mood disorders, use of antidepressant treatments | |||
| No | 617 809 (89.6) | 610 159 (88.5) | 0.04 |
| Yes | 71 466 (10.4) | 79 116 (11.5) | |
| Psychotic disorders, use of neuroleptics treatments | |||
| No | 680 647 (98.7) | 675 353 (98.0) | 0.06 |
| Yes | 8628 (1.3) | 13 922 (2.0) | |
| Dementias (including Alzheimer disease) | |||
| No | 683 401 (99.1) | 682 000 (98.9) | 0.02 |
| Yes | 5874 (0.9) | 7275 (1.1) | |
| Epilepsy | |||
| No | 685 812 (99.5) | 685 027 (99.4) | 0.02 |
| Yes | 3463 (0.5) | 4248 (0.6) | |
| Parkinson disease | |||
| No | 683 236 (99.1) | 681 850 (98.9) | 0.02 |
| Yes | 6039 (0.9) | 7425 (1.1) | |
| Chronic inflammatory bowel diseases | |||
| No | 685 482 (99.4) | 686 773 (99.6) | −0.03 |
| Yes | 3793 (0.6) | 2502 (0.4) | |
| Rheumatoid arthritis and related diseases | |||
| No | 683 125 (99.1) | 685 008 (99.4) | −0.03 |
| Yes | 6150 (0.9) | 4267 (0.6) | |
| Ankylosing spondylitis and related diseases | |||
| No | 685 396 (99.4) | 686 689 (99.6) | −0.03 |
| Yes | 3879 (0.6) | 2586 (0.4) | |
Table 2. Comparison of Ad26.COV2.S and BNT162b2 Vaccines in Terms of Risk of Hospitalization for COVID-19 in France.
| Follow-up intervals and vaccine | Participants, No. | Events, No. (%) | Follow-up, median (IQR), d | HR (95% CI)a | |
|---|---|---|---|---|---|
| Crude | Adjusted | ||||
| Day 0 to the end of follow-up | |||||
| BNT162b2 | 689 275 | 49 (0.01) | 82 (50-101) | 1 [Reference] | 1 [Reference] |
| Ad26.COV2.S | 689 275 | 285 (0.04) | 82 (49-101) | 5.82 (4.30-7.88) | 5.51 (4.11-7.40) |
| Day 14 to the end of follow-up | |||||
| BNT162b2 | 688 861 | 28 (0.00) | 68 (36-88) | 1 [Reference] | 1 [Reference] |
| Ad26.COV2.S | 688 861 | 203 (0.03) | 68 (36-87) | 7.26 (4.89-10.77) | 6.70 (4.59-9.75) |
| Day 28 to the end of follow-up | |||||
| BNT162b2 | 688 263 | 23 (0.00) | 54 (22-74) | 1 [Reference] | 1 [Reference] |
| Ad26.COV2.S | 688 263 | 129 (0.02) | 54 (22-74) | 5.61 (3.60-8.75) | 5.16 (3.39-7.85) |
Abbreviation: HR, hazard ratio.
HRs were obtained from inverse probability of treatment weighted Cox models taking into account all the variables described in Table 1.
Discussion
This comparative effectiveness research study, which, to our knowledge, is the largest estimating effectiveness of Ad26.COV2.S in the general population, included almost the entire population aged 55 years or older vaccinated with Ad26.COV2.S in France. Considering the high rate of vaccination uptake in this population, using an active comparator was more relevant than considering unvaccinated individuals as controls. The risk of severe COVID–19 related hospitalization after vaccination was approximately 5 times higher with Ad26.COV2.S than with BNT162b2.
On the basis of these results and an effectiveness of BNT162b2 of 92% (95% CI, 90%-94%) estimated from the same data set,6 we obtained an absolute effectiveness of Ad26.COV2.S of 59% (95% CI, 33%-75%). This finding is consistent with previous estimates of smaller populations and using test-negative or case-control designs.2,3 A limitation of this study is that, although the 2 vaccine groups were matched on vaccination day, age, sex, and area of residence and the associations were adjusted for a large number of covariables, we cannot completely exclude residual confounding. Using the active BNT162b2 vaccine comparator likely lowered this potential bias compared with using an unvaccinated group. The slightly higher risk estimates from day 0 or 14 are likely associated with partial protection by the first dose of BNT162b2 combined with delayed protection of Ad26.COV2.S immediately in the days after injection.
Conclusions
This study found that the Ad26.COV2.S vaccine is less effective against COVID-19–related hospitalization than the BNT162b2 vaccine. These results strengthen the evidence supporting a second dose in people who received the Ad26.COV2.S vaccine by an mRNA vaccine as recommended in both France and the US.
eAppendix. Supplemental Methods
eReferences
References
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Associated Data
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Supplementary Materials
eAppendix. Supplemental Methods
eReferences