BY-COVID - WP5 - Baseline Use Case: COVID-19 vaccine effectiveness assessment

Descriptive analyses

Periods

Different time periods are specified for the analysis:

  • The data extraction period: Data extraction is foreseen from the first date of a documented SARS-CoV-2 infection in the population until the most recent date at which data is available at the time of analysis. All individuals vaccinated with at least one dose of the SARS-CoV-2 vaccine (any of the available brands) and all individuals eligible to be vaccinated with a documented positive diagnosis (irrespective of the type of test) for SARS-CoV-2 infection during the data extraction period are included in the study population.
  • The enrollment period: A sequence of nested (daily) trials are emulated with increasing time (t1, t2, …, tn), iterating over the days in the enrollment period. At each eligible time during the enrollment period, the vaccination status of eligible individuals is assessed and every individual who has completed a primary vaccination schedule at that time (coded here as initiation of the intervention strategy when emulating a nested target trial) is matched to an individual who has not (yet) completed the primary vaccination schedule (coded here as the control strategy when emulating a nested target trial).
  • The study period: The study period is considered from the start of the enrollment period until one year after the end of the enrollment period, to allow a minimal possible follow-up period of one year.
Period Time range
Data extraction period 2020-09-01 - 2024-04-05
Enrollment period 2021-02-02 - 2021-08-31
Study period 2021-01-01 - 2022-08-31

Study population and enrollment

A flow diagram displaying the process of obtaining a matched study population considered for survival analysis.

Description of the study population: table 1

Table 1
Completed a primary vaccination schedule during the enrollment period
(N=2123328)
Not completed a primary vaccination schedule during the enrollment period
(N=697285)
P-value

5-year age groups

sex_cd
1 1019290 (48.0%) 343475 (49.3%) <0.001
2 1104038 (52.0%) 353810 (50.7%)
age_cd
10 170927 (8.1%) 32306 (4.6%) <0.001
11 185092 (8.7%) 27729 (4.0%)
12 195044 (9.2%) 23020 (3.3%)
13 194349 (9.2%) 18367 (2.6%)
14 179502 (8.5%) 14377 (2.1%)
15 158875 (7.5%) 12431 (1.8%)
16 110856 (5.2%) 9612 (1.4%)
17 76632 (3.6%) 7730 (1.1%)
18 81108 (3.8%) 9649 (1.4%)
2 11.0 (0.0%) 77059 (11.1%)
3 10611 (0.5%) 121717 (17.5%)
4 80797 (3.8%) 86070 (12.3%)
5 118337 (5.6%) 53752 (7.7%)
6 119579 (5.6%) 53672 (7.7%)
7 134279 (6.3%) 56726 (8.1%)
8 140687 (6.6%) 48514 (7.0%)
9 152447 (7.2%) 40357 (5.8%)
Missing 14195 (0.7%) 4197 (0.6%)
residence_area_cd
BE100 378582 (17.8%) 192314 (27.6%) <0.001
BE310 206241 (9.7%) 60654 (8.7%)
BE323 118899 (5.6%) 38816 (5.6%)
BE328 109704 (5.2%) 23415 (3.4%)
BE329 67939 (3.2%) 21064 (3.0%)
BE32A 67158 (3.2%) 17088 (2.5%)
BE32B 177620 (8.4%) 61185 (8.8%)
BE32C 55404 (2.6%) 15384 (2.2%)
BE32D 48379 (2.3%) 11946 (1.7%)
BE331 60910 (2.9%) 15443 (2.2%)
BE332 287820 (13.6%) 85172 (12.2%)
BE334 48211 (2.3%) 10160 (1.5%)
BE335 98081 (4.6%) 34609 (5.0%)
BE336 29958 (1.4%) 8407 (1.2%)
BE341 17399 (0.8%) 4789 (0.7%)
BE342 19634 (0.9%) 6062 (0.9%)
BE343 29564 (1.4%) 7622 (1.1%)
BE344 31218 (1.5%) 8946 (1.3%)
BE345 21526 (1.0%) 6117 (0.9%)
BE351 58081 (2.7%) 15300 (2.2%)
BE352 156522 (7.4%) 44381 (6.4%)
BE353 34478 (1.6%) 8411 (1.2%)
essential_worker_bl
Yes 117847 (5.6%) 21567 (3.1%) <0.001
No 2005481 (94.4%) 675718 (96.9%)
institutionalized_bl
Yes 17562 (0.8%) 1498 (0.2%) <0.001
No 2105766 (99.2%) 695787 (99.8%)
socecon_lvl_cd
high 620180 (29.2%) 133678 (19.2%) <0.001
low 859436 (40.5%) 376455 (54.0%)
middle 643492 (30.3%) 187060 (26.8%)
Missing 220 (0.0%) 92.0 (0.0%)
comorbidities_bl
Yes 549014 (25.9%) 65621 (9.4%) <0.001
No 1574314 (74.1%) 631664 (90.6%)
immunestatus_bl
Yes 60697 (2.9%) 8303 (1.2%) <0.001
No 2062631 (97.1%) 688982 (98.8%)
Table 1
Intervention group
(N=2123328)
Control group
(N=2123328)
P-value

5-year age groups

sex_cd
1 1019290 (48.0%) 1019188 (48.0%) 0.922
2 1104038 (52.0%) 1104140 (52.0%)
age_cd
10 172450 (8.1%) 172491 (8.1%) 1
11 187065 (8.8%) 187339 (8.8%)
12 195884 (9.2%) 196027 (9.2%)
13 195720 (9.2%) 195937 (9.2%)
14 181337 (8.5%) 181386 (8.5%)
15 159808 (7.5%) 159781 (7.5%)
16 111346 (5.2%) 111268 (5.2%)
17 76969 (3.6%) 76862 (3.6%)
18 81300 (3.8%) 81224 (3.8%)
2 35.0 (0.0%) 34.0 (0.0%)
3 10926 (0.5%) 10895 (0.5%)
4 81026 (3.8%) 80966 (3.8%)
5 118530 (5.6%) 118468 (5.6%)
6 120852 (5.7%) 120777 (5.7%)
7 135461 (6.4%) 135357 (6.4%)
8 141127 (6.6%) 141099 (6.6%)
9 153492 (7.2%) 153417 (7.2%)
residence_area_cd
BE100 378582 (17.8%) 378630 (17.8%) 1
BE310 206241 (9.7%) 206257 (9.7%)
BE323 118899 (5.6%) 118895 (5.6%)
BE328 109704 (5.2%) 109706 (5.2%)
BE329 67939 (3.2%) 67948 (3.2%)
BE32A 67158 (3.2%) 67146 (3.2%)
BE32B 177620 (8.4%) 177640 (8.4%)
BE32C 55404 (2.6%) 55395 (2.6%)
BE32D 48379 (2.3%) 48367 (2.3%)
BE331 60910 (2.9%) 60910 (2.9%)
BE332 287820 (13.6%) 287824 (13.6%)
BE334 48211 (2.3%) 48200 (2.3%)
BE335 98081 (4.6%) 98094 (4.6%)
BE336 29958 (1.4%) 29951 (1.4%)
BE341 17399 (0.8%) 17397 (0.8%)
BE342 19634 (0.9%) 19629 (0.9%)
BE343 29564 (1.4%) 29559 (1.4%)
BE344 31218 (1.5%) 31205 (1.5%)
BE345 21526 (1.0%) 21519 (1.0%)
BE351 58081 (2.7%) 58071 (2.7%)
BE352 156522 (7.4%) 156513 (7.4%)
BE353 34478 (1.6%) 34472 (1.6%)
essential_worker_bl
Yes 117847 (5.6%) 117817 (5.5%) 0.951
No 2005481 (94.4%) 2005511 (94.5%)
institutionalized_bl
Yes 17562 (0.8%) 17279 (0.8%) 0.129
No 2105766 (99.2%) 2106049 (99.2%)
socecon_lvl_cd
high 620238 (29.2%) 620062 (29.2%) 0.975
low 859540 (40.5%) 859750 (40.5%)
middle 643550 (30.3%) 643516 (30.3%)
comorbidities_bl
Yes 549014 (25.9%) 549024 (25.9%) 0.992
No 1574314 (74.1%) 1574304 (74.1%)
immunestatus_bl
Yes 60697 (2.9%) 60477 (2.8%) 0.523
No 2062631 (97.1%) 2062851 (97.2%)

Vaccination over time

The cumulative frequency of individuals completing a primary vaccination schedule during the enrollment period is plotted over time, as well as the cumulative frequency of individuals completing a primary vaccination schedule with a specific vaccination schedule.

Two-by-two tables

The imported dataset contains 3 948 815 individual-level records. The individuals are counted by whether they were fully vaccinated within the enrollment period and whether they experienced a known/confirmed infection (confirmed_case_bl, see CDM for definition).

Confirmed case No confirmed case Total
Completed a primary vaccination schedule during the enrollment period 682295 2070432 2752727
Didn’t complete a primary vaccination schedule during the enrollment period 629604 566484 1196088
Total 1311899 2636916 3948815

From the individuals in the original input data, 1 128 202 individuals were excluded (experienced a previous infection, not complying with validation rules, listwise deletion), ending up with 2 820 613 individuals eligible for analysis. The individuals eligible for analysis are counted by whether they were fully vaccinated within the enrollment period and whether they experienced a known/confirmed infection (confirmed_case_bl, see CDM for definition).

Confirmed case No confirmed case Total
Completed a primary vaccination schedule during the enrollment period 465876 1657452 2123328
Didn’t complete a primary vaccination schedule during the enrollment period 415449 281836 697285
Total 881325 1939288 2820613

At each eligible time during the enrollment period, the vaccination status of eligible individuals is assessed and every individual who has completed a primary vaccination schedule at that time (treated/exposed) is matched to an individual who has not (yet) completed the primary vaccination schedule (control). 2 123 328 eligible individuals completed a primary vaccination schedule during the enrollment period. Newly vaccinated individuals (completing a primary vaccination schedule) are eligible for inclusion in the study, even if they had previously been selected in the “no (or partial) vaccine group”. As such, individuals can occur more than once in the matched population (1 070 871 individuals completing a primary vaccination schedule during the enrollment period were previously matched once or more than once as control). The matched individuals are counted by intervention group and whether they experienced a known/confirmed infection (confirmed_case_bl, see CDM for definition).

Confirmed case No confirmed case Total
Intervention group 465876 1657452 2123328
Control group 663528 1459800 2123328
Total 1129404 3117252 4246656

Survival in un-matched population

Variable Beta (SE) HR (95% CI) P
fully_vaccinated_bl_bisTRUE -1.05 (0.00) 0.35 (0.35, 0.35) <0.001
Strata Time Number at risk Cumulative sum of number of events Cumulative sum of number censored Survival Std. error Cumulative hazard Std. error cumulative hazard
Fully vaccinated 0 696555 163 3 0.99976599 1.832684e-05 2.340088e-04 1.832898e-05
Fully vaccinated 1 696389 313 10 0.99955064 2.539335e-05 4.494057e-04 2.540191e-05
Fully vaccinated 100 641339 52351 3357 0.92470220 3.164713e-04 7.824661e-02 3.420786e-04
Fully vaccinated 200 534945 95768 66190 0.86015684 4.196076e-04 1.505669e-01 4.875887e-04
Fully vaccinated 300 386177 152751 162378 0.75925192 5.443377e-04 2.752370e-01 7.164170e-04
Fully vaccinated 400 65558 363780 268874 0.19146722 6.597135e-04 1.630403e+00 3.381077e-03
Fully vaccinated 500 29633 397711 269335 0.08934059 4.882662e-04 2.388426e+00 5.408210e-03
Fully vaccinated 600 20894 406251 269441 0.06343474 4.195211e-04 2.730020e+00 6.561148e-03
Fully vaccinated 0 2123328 406341 269451 0.99995761 4.467813e-06 4.238629e-05 4.467907e-06
Fully vaccinated 1 2123228 406417 269464 0.99992182 6.067656e-06 7.818085e-05 6.068010e-06
Fully vaccinated 100 2077420 431074 292465 0.98826585 7.404027e-05 1.180243e-02 7.491235e-05
Fully vaccinated 200 588871 588129 1630820 0.87718293 2.910796e-04 1.309525e-01 3.315894e-04
Fully vaccinated 300 277657 625309 1896812 0.80113436 4.681035e-04 2.215925e-01 5.839700e-04
Fully vaccinated 400 121070 633357 2048624 0.77501296 5.394392e-04 2.547356e-01 6.957256e-04
Fully vaccinated 500 6665 636124 2156265 0.68316268 2.323411e-03 3.807600e-01 3.396981e-03
Fully vaccinated 600 1633 637286 2160122 0.45831788 6.077732e-03 7.788935e-01 1.322366e-02
Variable Beta (SE) HR (95% CI) P
fully_vaccinated_bl_bisTRUE -0.85 (0.00) 0.43 (0.42, 0.43) <0.001
sex_cd
     1 (ref)
     2 0.13 (0.00) 1.14 (1.13, 1.14) <0.001
age_cd
     2 (ref)
     3 -0.17 (0.01) 0.85 (0.84, 0.85) <0.001
     4 -0.25 (0.01) 0.78 (0.77, 0.79) <0.001
     5 -0.32 (0.01) 0.73 (0.72, 0.74) <0.001
     6 -0.17 (0.01) 0.85 (0.84, 0.86) <0.001
     7 -0.14 (0.01) 0.87 (0.86, 0.88) <0.001
     8 -0.12 (0.01) 0.89 (0.88, 0.90) <0.001
     9 -0.19 (0.01) 0.83 (0.82, 0.84) <0.001
     10 -0.35 (0.01) 0.71 (0.70, 0.72) <0.001
     11 -0.50 (0.01) 0.61 (0.60, 0.62) <0.001
     12 -0.66 (0.01) 0.52 (0.51, 0.52) <0.001
     13 -0.84 (0.01) 0.43 (0.43, 0.44) <0.001
     14 -1.03 (0.01) 0.36 (0.35, 0.36) <0.001
     15 -1.16 (0.01) 0.31 (0.31, 0.32) <0.001
     16 -1.23 (0.01) 0.29 (0.28, 0.30) <0.001
     17 -1.21 (0.02) 0.30 (0.29, 0.31) <0.001
     18 -1.03 (0.01) 0.36 (0.35, 0.37) <0.001
residence_area_cd
     BE100 (ref)
     BE310 0.05 (0.00) 1.05 (1.04, 1.06) <0.001
     BE323 -0.10 (0.01) 0.90 (0.89, 0.91) <0.001
     BE328 -0.18 (0.01) 0.83 (0.82, 0.85) <0.001
     BE329 0.01 (0.01) 1.01 (0.99, 1.02) 0.39
     BE32A -0.18 (0.01) 0.83 (0.82, 0.85) <0.001
     BE32B -0.04 (0.00) 0.96 (0.95, 0.97) <0.001
     BE32C 0.01 (0.01) 1.01 (0.99, 1.02) 0.35
     BE32D -0.07 (0.01) 0.93 (0.91, 0.95) <0.001
     BE331 -0.00 (0.01) 1.00 (0.98, 1.01) 0.67
     BE332 -0.05 (0.00) 0.95 (0.94, 0.96) <0.001
     BE334 0.03 (0.01) 1.03 (1.01, 1.05) <0.001
     BE335 -0.12 (0.01) 0.89 (0.88, 0.90) <0.001
     BE336 0.00 (0.01) 1.00 (0.98, 1.03) 0.78
     BE341 -0.08 (0.02) 0.92 (0.90, 0.95) <0.001
     BE342 -0.03 (0.01) 0.97 (0.94, 0.99) 0.02
     BE343 -0.04 (0.01) 0.96 (0.94, 0.99) 0.002
     BE344 0.04 (0.01) 1.04 (1.01, 1.06) <0.001
     BE345 -0.02 (0.01) 0.98 (0.95, 1.00) 0.08
     BE351 -0.02 (0.01) 0.98 (0.97, 1.00) 0.04
     BE352 -0.01 (0.01) 0.99 (0.98, 1.00) 0.13
     BE353 -0.21 (0.01) 0.81 (0.79, 0.83) <0.001
essential_worker_blTRUE -0.11 (0.01) 0.90 (0.89, 0.91) <0.001
institutionalized_blTRUE 0.23 (0.03) 1.26 (1.20, 1.33) <0.001
socecon_lvl_cd
     high (ref)
     low -0.20 (0.00) 0.82 (0.81, 0.82) <0.001
     middle -0.04 (0.00) 0.96 (0.95, 0.97) <0.001
comorbidities_blTRUE 0.00 (0.00) 1.00 (0.99, 1.01) 0.91
immunestatus_blTRUE -0.02 (0.01) 0.98 (0.96, 1.01) 0.13