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 2020-01-01 - 2022-12-20
Enrollment period 2021-01-22 - 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=2588318)
Not completed a primary vaccination schedule during the enrollment period
(N=2263277)
P-value

ᵃ5-year age groups

sex_cd
1 1209685 (46.7%) 1184459 (52.3%) <0.001
2 1378633 (53.3%) 1078818 (47.7%)
age_cdᵃ
10 195696 (7.6%) 90088 (4.0%) <0.001
11 246049 (9.5%) 80071 (3.5%)
12 270896 (10.5%) 72732 (3.2%)
13 280746 (10.8%) 61802 (2.7%)
14 296567 (11.5%) 51760 (2.3%)
15 300864 (11.6%) 43919 (1.9%)
16 179299 (6.9%) 30545 (1.3%)
17 125315 (4.8%) 34565 (1.5%)
18 93313 (3.6%) 56945 (2.5%)
3 2242 (0.1%) 274985 (12.1%)
4 37872 (1.5%) 224984 (9.9%)
5 55185 (2.1%) 217002 (9.6%)
6 79327 (3.1%) 233172 (10.3%)
7 99915 (3.9%) 210038 (9.3%)
8 140313 (5.4%) 180610 (8.0%)
9 184719 (7.1%) 126999 (5.6%)
2 0 (0%) 273060 (12.1%)
residence_area_cd
FI193 123557 (4.8%) 127817 (5.6%) <0.001
FI194 86825 (3.4%) 91502 (4.0%)
FI195 83398 (3.2%) 75810 (3.3%)
FI196 105950 (4.1%) 93195 (4.1%)
FI197 240957 (9.3%) 241720 (10.7%)
FI1B1 782721 (30.2%) 597379 (26.4%)
FI1C1 228877 (8.8%) 201234 (8.9%)
FI1C2 84240 (3.3%) 72985 (3.2%)
FI1C3 107218 (4.1%) 82096 (3.6%)
FI1C4 78510 (3.0%) 59378 (2.6%)
FI1C5 65077 (2.5%) 42368 (1.9%)
FI1D1 73566 (2.8%) 50941 (2.3%)
FI1D2 113916 (4.4%) 117934 (5.2%)
FI1D3 78493 (3.0%) 74195 (3.3%)
FI1D5 34401 (1.3%) 27944 (1.2%)
FI1D7 82028 (3.2%) 80957 (3.6%)
FI1D8 33965 (1.3%) 32983 (1.5%)
FI1D9 184619 (7.1%) 192839 (8.5%)
essential_worker_bl
Yes 221391 (8.6%) 172063 (7.6%) <0.001
No 2365934 (91.4%) 2048942 (90.5%)
Missing 993 (0.0%) 42272 (1.9%)
socecon_lvl_cd
1 376469 (14.5%) 311272 (13.8%) <0.001
2 570270 (22.0%) 633469 (28.0%)
3 1640586 (63.4%) 1276264 (56.4%)
Missing 993 (0.0%) 42272 (1.9%)
comorbidities_bl
Yes 1109074 (42.8%) 430287 (19.0%) <0.001
No 1479244 (57.2%) 1832990 (81.0%)
immunestatus_bl
Yes 575741 (22.2%) 194678 (8.6%) <0.001
No 2012577 (77.8%) 2068599 (91.4%)
Table 1
Intervention group
(N=2588318)
Control group
(N=2588318)
P-value

ᵃ5-year age groups

sex_cd
1 1209685 (46.7%) 1209663 (46.7%) 0.985
2 1378633 (53.3%) 1378655 (53.3%)
age_cdᵃ
10 195696 (7.6%) 195716 (7.6%) 1
11 246049 (9.5%) 246075 (9.5%)
12 270896 (10.5%) 270930 (10.5%)
13 280746 (10.8%) 280777 (10.8%)
14 296567 (11.5%) 296490 (11.5%)
15 300864 (11.6%) 300835 (11.6%)
16 179299 (6.9%) 179299 (6.9%)
17 125315 (4.8%) 125315 (4.8%)
18 93313 (3.6%) 93313 (3.6%)
3 2242 (0.1%) 2242 (0.1%)
4 37872 (1.5%) 37869 (1.5%)
5 55185 (2.1%) 55181 (2.1%)
6 79327 (3.1%) 79328 (3.1%)
7 99915 (3.9%) 99910 (3.9%)
8 140313 (5.4%) 140320 (5.4%)
9 184719 (7.1%) 184717 (7.1%)
2 0 (0%) 1 (0.0%)
residence_area_cd
FI193 123557 (4.8%) 123555 (4.8%) 1
FI194 86825 (3.4%) 86821 (3.4%)
FI195 83398 (3.2%) 83395 (3.2%)
FI196 105950 (4.1%) 105950 (4.1%)
FI197 240957 (9.3%) 240960 (9.3%)
FI1B1 782721 (30.2%) 782732 (30.2%)
FI1C1 228877 (8.8%) 228879 (8.8%)
FI1C2 84240 (3.3%) 84241 (3.3%)
FI1C3 107218 (4.1%) 107217 (4.1%)
FI1C4 78510 (3.0%) 78510 (3.0%)
FI1C5 65077 (2.5%) 65082 (2.5%)
FI1D1 73566 (2.8%) 73562 (2.8%)
FI1D2 113916 (4.4%) 113916 (4.4%)
FI1D3 78493 (3.0%) 78494 (3.0%)
FI1D5 34401 (1.3%) 34395 (1.3%)
FI1D7 82028 (3.2%) 82028 (3.2%)
FI1D8 33965 (1.3%) 33963 (1.3%)
FI1D9 184619 (7.1%) 184618 (7.1%)
essential_worker_bl
Yes 221514 (8.6%) 221465 (8.6%) 0.94
No 2366804 (91.4%) 2366853 (91.4%)
socecon_lvl_cd
1 376578 (14.5%) 376517 (14.5%) 0.997
2 570719 (22.0%) 570751 (22.1%)
3 1641021 (63.4%) 1641050 (63.4%)
comorbidities_bl
Yes 1109074 (42.8%) 1109051 (42.8%) 0.984
No 1479244 (57.2%) 1479267 (57.2%)
immunestatus_bl
Yes 575741 (22.2%) 575687 (22.2%) 0.955
No 2012577 (77.8%) 2012631 (77.8%)

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 5 308 428 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 513675 2239262 2752937
Didn’t complete a primary vaccination schedule during the enrollment period 637299 1918192 2555491
Total 1150974 4157454 5308428

From the individuals in the original input data, 456 833 individuals were excluded (experienced a previous infection, not complying with validation rules, listwise deletion), ending up with 4 851 595 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 413184 2175134 2588318
Didn’t complete a primary vaccination schedule during the enrollment period 506192 1757085 2263277
Total 919376 3932219 4851595

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). 2 588 318 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 (1 391 844 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 413184 2175134 2588318
Control group 405647 2182671 2588318
Total 818831 4357805 5176636

Survival in un-matched population

Variable Beta (SE) HR (95% CI) P
fully_vaccinated_bl_bisTRUE -0.76 (0.00) 0.47 (0.46, 0.47) <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 2209782 78 227 0.9999647 3.996596e-06 3.529760e-05 3.996666e-06
Fully vaccinated 1 2209477 234 488 0.9998941 6.922536e-06 1.059025e-04 6.923066e-06
Fully vaccinated 100 2108593 66516 37052 0.9696444 1.159049e-04 3.081954e-02 1.195087e-04
Fully vaccinated 200 1520780 207681 483261 0.8966171 2.163259e-04 1.090888e-01 2.411846e-04
Fully vaccinated 300 1233553 265179 717530 0.8603589 2.551633e-04 1.503591e-01 2.964873e-04
Fully vaccinated 400 673235 357664 1179611 0.7659567 3.738348e-04 2.664956e-01 4.877637e-04
Fully vaccinated 500 590345 436466 1183223 0.6759245 4.467791e-04 3.914338e-01 6.605165e-04
Fully vaccinated 600 578070 447428 1184365 0.6633560 4.543124e-04 4.102011e-01 6.844074e-04
Fully vaccinated 0 2588318 447442 1184374 0.9999946 1.445590e-06 5.408918e-06 1.445594e-06
Fully vaccinated 1 2588295 447499 1184395 0.9999726 3.255418e-06 2.743114e-05 3.255477e-06
Fully vaccinated 100 2564756 454453 1201352 0.9972777 3.243511e-05 2.725918e-03 3.252306e-05
Fully vaccinated 200 488116 527637 3216299 0.9543591 1.817578e-04 4.670355e-02 1.903937e-04
Fully vaccinated 300 154967 551398 3514107 0.8635385 6.090022e-04 1.466514e-01 7.048880e-04
Fully vaccinated 400 48052 557598 3616568 0.8218618 7.978153e-04 1.961048e-01 9.703663e-04
Fully vaccinated 500 1969 558350 3659893 0.7750689 2.499569e-03 2.547028e-01 3.223538e-03
Fully vaccinated 600 2 558377 3661732 0.7235240 3.112404e-02 3.226032e-01 4.213002e-02
Variable Beta (SE) HR (95% CI) P
fully_vaccinated_bl_bisTRUE -0.44 (0.00) 0.64 (0.64, 0.65) <0.001
sex_cd
     1 (ref)
     2 0.13 (0.00) 1.14 (1.14, 1.15) <0.001
age_cd
     2 (ref)
     3 0.27 (0.01) 1.31 (1.29, 1.32) <0.001
     4 1.06 (0.01) 2.88 (2.85, 2.92) <0.001
     5 1.06 (0.01) 2.89 (2.86, 2.93) <0.001
     6 0.98 (0.01) 2.66 (2.63, 2.69) <0.001
     7 0.95 (0.01) 2.58 (2.55, 2.61) <0.001
     8 0.96 (0.01) 2.62 (2.59, 2.65) <0.001
     9 0.88 (0.01) 2.41 (2.38, 2.44) <0.001
     10 0.68 (0.01) 1.97 (1.94, 2.00) <0.001
     11 0.41 (0.01) 1.50 (1.48, 1.52) <0.001
     12 0.13 (0.01) 1.14 (1.12, 1.16) <0.001
     13 -0.42 (0.01) 0.66 (0.64, 0.67) <0.001
     14 -0.80 (0.01) 0.45 (0.44, 0.46) <0.001
     15 -1.00 (0.02) 0.37 (0.36, 0.38) <0.001
     16 -0.93 (0.02) 0.39 (0.38, 0.41) <0.001
     17 -0.62 (0.02) 0.54 (0.52, 0.56) <0.001
     18 -0.17 (0.02) 0.84 (0.82, 0.87) <0.001
residence_area_cd
     FI193 (ref)
     FI194 -0.02 (0.01) 0.98 (0.96, 1.00) 0.05
     FI195 0.50 (0.01) 1.64 (1.61, 1.67) <0.001
     FI196 0.13 (0.01) 1.14 (1.12, 1.16) <0.001
     FI197 0.16 (0.01) 1.18 (1.16, 1.19) <0.001
     FI1B1 0.26 (0.01) 1.30 (1.28, 1.32) <0.001
     FI1C1 0.02 (0.01) 1.02 (1.00, 1.03) 0.05
     FI1C2 0.16 (0.01) 1.18 (1.15, 1.20) <0.001
     FI1C3 0.32 (0.01) 1.38 (1.36, 1.41) <0.001
     FI1C4 0.16 (0.01) 1.18 (1.15, 1.20) <0.001
     FI1C5 0.00 (0.01) 1.00 (0.98, 1.03) 0.89
     FI1D1 0.49 (0.01) 1.63 (1.60, 1.67) <0.001
     FI1D2 -0.04 (0.01) 0.96 (0.94, 0.98) <0.001
     FI1D3 0.04 (0.01) 1.04 (1.02, 1.06) <0.001
     FI1D5 0.26 (0.01) 1.30 (1.27, 1.33) <0.001
     FI1D7 0.09 (0.01) 1.10 (1.08, 1.12) <0.001
     FI1D8 0.62 (0.01) 1.86 (1.82, 1.90) <0.001
     FI1D9 0.09 (0.01) 1.10 (1.08, 1.11) <0.001
essential_worker_blTRUE 0.43 (0.00) 1.53 (1.52, 1.55) <0.001
socecon_lvl_cd
     1 (ref)
     2 0.05 (0.00) 1.05 (1.04, 1.06) <0.001
     3 -0.23 (0.00) 0.79 (0.79, 0.80) <0.001
comorbidities_blTRUE 0.02 (0.00) 1.02 (1.01, 1.03) <0.001
immunestatus_blTRUE 0.10 (0.00) 1.10 (1.09, 1.11) <0.001