TABLE 3.
Risk of SARS-CoV-2 reinfection and severe/critical COVID-19 among vaccinated vs. unvaccinated subjects, overall, and stratified by definition of reinfection, number of vaccine doses, length of follow-up, predominant strain, study design and risk exposure.
| Pooled estimates | Raw datab | |||||||
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| Analyses | N. datasets | OR (95% CI) | P-value | I2, % | No. of events | Vaccinated subjects | No. of events | Unvaccinated subjects |
| (total sample)a | ||||||||
| SARS-CoV-2 reinfection—all studies (4, 6, 8, 21–34) | 21(18,132,192) | 0.47(0.42−0.54) | <0.001 | 98 | 37,440 | 13,462,121 | 134,598 | 4,670,071 |
| - Adjusted estimates only (4, 6, 8, 21–24, 26, 28–32, 34) | 17(17,937,601) | 0.47(0.41−0.54) | <0.001 | 98 | 35,105 | 13,348,646 | 132,525 | 4,588,955 |
| 1. Time-lag ≥ 90 days c (4, 7, 21–26, 29, 31–34) | 15(373,109) | 0.44(0.36−0.54) | <0.001 | 97 | 13,411 | 223,473 | 109,540 | 149,636 |
| - Adjusted estimates only (4, 21–24, 26, 29, 31, 32, 34) | 13(367,498) | 0.46(0.37−0.56) | <0.001 | 97 | 13,379 | 221,827 | 109,182 | 145,671 |
| 2. Number of vaccine doses: d | ||||||||
| - Partially vaccinated subjects (4, 8, 23, 24, 26, 28, 30–32) | 11(5,248,720) | 0.58(0.44−0.77) | 0.004 | 98 | 5,820 | 729,103 | 127,701 | 4,509,617 |
| - Fully vaccinated subjects (4, 8, 21–24, 26, 28, 30–32) | 13(17,036,021) | 0.45(0.40−0.50) | <0.001 | 95 | 28,508 | 12,521,565 | 129,316 | 4,514,456 |
| - Boosted subjects (3 doses) (4, 24, 30) | 4(11,365,430) | 0.46(0.29−0.73) | 0.001 | 99 | 1,675 | 7,709,207 | 25,631 | 3,656,223 |
| 3. Length of follow-up: | ||||||||
| - <6 months (< 120 days)—all studies (8, 26, 27) | 4(1,876,028) | 0.52(0.40−0.67) | <0.001 | 99 | 9,964 | 935,957 | 18,761 | 940,071 |
| - Adjusted estimates only (8, 26) | 2(1,603,758) | 0.47(0.30−0.74) | 0.001 | 99 | 7,661 | 824,128 | 17,036 | 862,920 |
| - ≥6 months (≥ 120 days)—all studies (4, 6, 7, 25, 28–34) | 12(16,317,474) | 0.45(0.34−0.59) | 0.005 | 98 | 24,943 | 12,514,920 | 28,620 | 3,802,554 |
| - Studies with adjusted estimates only (4, 6, 7, 28–32, 34) | 10(16,311,863) | 0.47(0.35−0.63) | 0.05 | 99 | 24,911 | 12,513,274 | 28,262 | 3,798,589 |
| 4. Predominant viral strain: | ||||||||
| - Delta variant (B.1.617.2)—all studies (8, 22, 24, 25, 27, 31–33) | 10(1,948,597) | 0.40(0.31−0.50) | <0.001 | 97 | 4,099 | 994,162 | 9,877 | 954,435 |
| - Adjusted estimates only (8, 22, 24, 31, 32) | 7(1,792,675) | 0.38(0.30−0.49) | <0.001 | 96 | 3,284 | 912,090 | 8,416 | 880,585 |
| - Omicron variant (B.1.1.529)—all studies (4, 6, 23, 24, 27, 28, 30) | 7(16,107,318) | 0.58(0.48−0.70) | <0.001 | 97 | 26,587 | 12,406,936 | 26,662 | 3,700,382 |
| - Adjusted estimates only (4, 6, 23, 24, 28, 30) | 6(15,951,396) | 0.59(0.48−0.73) | <0.001 | 96 | 25,772 | 12,324,864 | 25,01 | 3,626,532 |
| 5. Risk of exposure: | ||||||||
| - General population—all studies (4, 6, 8, 21, 22, 24–28, 30, 31) | 15(18,123,901) | 0.47(0.41−0.53) | <0.001 | 98 | 37,179 | 13,455,954 | 134,262 | 4,667,947 |
| - Adjusted estimates only (4, 6, 8, 21, 22, 24, 26, 28, 30, 31) | 11(17,930,759) | 0.46(0.37−0.55) | <0.001 | 98 | 34,856 | 13,343,270 | 132,195 | 4,587,489 |
| - Healthcare workers—all studies (23, 29, 31–34) | 6(8,291) | 0.50(0.41−0.61) | <0.001 | 0 | 261 | 6,167 | 336 | 2,124 |
| - Adjusted estimates only (23, 29, 31, 32, 34) | 5(6,842) | 0.49(0.40−0.61) | <0.001 | 0 | 249 | 5,376 | 320 | 1,466 |
| 6. Study design: | ||||||||
| - Cohort—all studies (6, 8, 25, 27–34) | 14(18,014,945) | 0.44(0.36−0.54) | <0.001 | 98 | 24,919 | 13,381,593 | 29,000 | 4,633,352 |
| - Adjusted estimates only (6, 8, 28–32, 34) | 10(17,820,354) | 0.44(0.33−0.57) | <0.001 | 98 | 22,584 | 13,268,118 | 26,917 | 4,552,236 |
| - Case-control—all studies (4, 21–24, 26) | 7(117,247) | 0.54(0.48−0.61) | <0.001 | 89 | 12,521 | 80,528 | 105,598 | 36,719 |
| Severe or critical/lethal COVID-19 e (8, 22, 24, 26, 29, 32) | 7(2,312,703) | 0.45(0.38−0.54) | <0.001 | 91 | 1,411 | 1,536,917 | 2,657 | 775,786 |
| 1. Number of vaccine doses: d | ||||||||
| - Partially vaccinated subjects (8, 24, 26, 32) | 5(982,721) | 0.35(0.21−0.60) | 0.02 | 91 | 474 | 48,4471 | 3,693 | 498,250 |
| - Fully vaccinated subjects (8, 22, 24, 26, 32) | 6(597,193) | 0.34(0.24−0.49) | <0.001 | 93 | 1,629 | 296,197 | 3,620 | 300,996 |
aThree studies (24, 27, 31) contributed with more than one dataset, thus the number of references does not always match the number of datasets included in each analysis (see “Results” for further details).
bNumber of events/Total number of previously infected and vaccinated subjects vs. Number of events/Total number of previously infected and unvaccinated subjects.
cThe risk of SARS-CoV-2 reinfection was computed: (1) using ≥ 45 days as the minimum time-lag between two positive episodes; (2) adopting a more stringent time-lag of 90 days (see Methods for further details).
dPartially vaccinated subjects: 1 dose of mRNA-1273, BNT162b2, ChAdOx1 nCoV-19, BBV152, BBIBP-CorV, Gam-COVID-Vac, or CoronaVac ≥ 14 days before reinfection; fully vaccinated subjects: ≥ 2 doses of mRNA-1273, BNT162b2, ChAdOx1 nCoV-19, BBV152, BBIBP-CorV, Gam-COVID-Vac or CoronaVac, or 1 dose of JNJ-78436735 ≥ 14 days before reinfection; boosted subjects: 3 doses of mRNA-1273, BNT162b2, ChAdOx1 nCoV-19, BBV152, BBIBP-CorV, Gam-COVID-Vac, or CoronaVac vaccines.
eSevere COVID-19: disease requiring hospital admission with no use of an intensive care unit; critical/lethal COVID-19: disease requiring admission in an intensive care unit and/or causing death. OR, Odds ratio; CI, confidence interval.