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 2020-03-01 - 2023-04-18
Enrollment period 2021-01-12 - 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=755055)
Not completed a primary vaccination schedule during the enrollment period
(N=244365)
P-value

ᵃ5-year age groups

sex_cd
1 360616 (47.8%) 126054 (51.6%) <0.001
2 394439 (52.2%) 118311 (48.4%)
age_cdᵃ
10 79881 (10.6%) 8180 (3.3%) <0.001
11 76979 (10.2%) 5995 (2.5%)
12 74495 (9.9%) 4556 (1.9%)
13 66025 (8.7%) 4653 (1.9%)
14 56885 (7.5%) 2458 (1.0%)
15 53710 (7.1%) 1276 (0.5%)
16 45802 (6.1%) 1013 (0.4%)
17 33447 (4.4%) 888 (0.4%)
18 45887 (6.1%) 1883 (0.8%)
3 318 (0.0%) 52280 (21.4%)
4 16314 (2.2%) 33824 (13.8%)
5 20863 (2.8%) 24530 (10.0%)
6 24610 (3.3%) 23541 (9.6%)
7 36643 (4.9%) 16814 (6.9%)
8 50711 (6.7%) 13937 (5.7%)
9 72485 (9.6%) 10592 (4.3%)
2 0 (0%) 37945 (15.5%)
residence_area_cd
ES241 124459 (16.5%) 40672 (16.6%) 0.0397
ES242 74181 (9.8%) 23672 (9.7%)
ES243 556415 (73.7%) 180021 (73.7%)
pregnancy_bl
Yes 13395 (1.8%) 9341 (3.8%) <0.001
No 741660 (98.2%) 235024 (96.2%)
essential_worker_bl
Yes 4991 (0.7%) 621 (0.3%) <0.001
No 750064 (99.3%) 243744 (99.7%)
institutionalized_bl
Yes 6661 (0.9%) 557 (0.2%) <0.001
No 748394 (99.1%) 243808 (99.8%)
foreign_bl
Yes 81524 (10.8%) 54225 (22.2%) <0.001
No 673531 (89.2%) 190140 (77.8%)
comorbidities_bl
Yes 326172 (43.2%) 28768 (11.8%) <0.001
No 428883 (56.8%) 215597 (88.2%)
immunestatus_bl
Yes 22630 (3.0%) 2016 (0.8%) <0.001
No 732425 (97.0%) 242349 (99.2%)
Table 1
Intervention group
(N=755055)
Control group
(N=755055)
P-value

ᵃ5-year age groups

sex_cd
1 360616 (47.8%) 360813 (47.8%) 0.749
2 394439 (52.2%) 394242 (52.2%)
age_cdᵃ
10 79881 (10.6%) 79920 (10.6%) 1
11 76979 (10.2%) 77022 (10.2%)
12 74495 (9.9%) 74525 (9.9%)
13 66025 (8.7%) 66019 (8.7%)
14 56885 (7.5%) 56873 (7.5%)
15 53710 (7.1%) 53708 (7.1%)
16 45802 (6.1%) 45795 (6.1%)
17 33447 (4.4%) 33428 (4.4%)
18 45887 (6.1%) 45876 (6.1%)
3 318 (0.0%) 318 (0.0%)
4 16314 (2.2%) 16313 (2.2%)
5 20863 (2.8%) 20857 (2.8%)
6 24610 (3.3%) 24609 (3.3%)
7 36643 (4.9%) 36628 (4.9%)
8 50711 (6.7%) 50703 (6.7%)
9 72485 (9.6%) 72461 (9.6%)
residence_area_cd
ES241 124459 (16.5%) 124505 (16.5%) 0.995
ES242 74181 (9.8%) 74173 (9.8%)
ES243 556415 (73.7%) 556377 (73.7%)
pregnancy_bl
Yes 13395 (1.8%) 13337 (1.8%) 0.725
No 741660 (98.2%) 741718 (98.2%)
essential_worker_bl
Yes 4991 (0.7%) 4958 (0.7%) 0.748
No 750064 (99.3%) 750097 (99.3%)
institutionalized_bl
Yes 6661 (0.9%) 6589 (0.9%) 0.536
No 748394 (99.1%) 748466 (99.1%)
foreign_bl
Yes 81524 (10.8%) 81495 (10.8%) 0.941
No 673531 (89.2%) 673560 (89.2%)
comorbidities_bl
Yes 326172 (43.2%) 326163 (43.2%) 0.99
No 428883 (56.8%) 428892 (56.8%)
immunestatus_bl
Yes 22630 (3.0%) 22621 (3.0%) 0.97
No 732425 (97.0%) 732434 (97.0%)

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 1 143 805 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 261239 547330 808569
Didn’t complete a primary vaccination schedule during the enrollment period 111848 223388 335236
Total 373087 770718 1143805

From the individuals in the original input data, 144 385 individuals were excluded (experienced a previous infection, not complying with validation rules, listwise deletion), ending up with 1e+06 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 258743 496312 755055
Didn’t complete a primary vaccination schedule during the enrollment period 110937 133428 244365
Total 369680 629740 999420

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). 755 055 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 (4e+05 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 258743 496312 755055
Control group 261426 493629 755055
Total 520169 989941 1510110

Survival in un-matched population

Variable Beta (SE) HR (95% CI) P
fully_vaccinated_bl_bisTRUE -0.81 (0.00) 0.44 (0.44, 0.45) <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 243356 75 36 0.9996918 3.558129e-05 0.0003081905 3.558677e-05
Fully vaccinated 1 243245 199 46 0.9991822 5.794912e-05 0.0008179646 5.798397e-05
Fully vaccinated 100 221252 20026 2461 0.9173256 5.595919e-04 0.0862466631 6.096977e-04
Fully vaccinated 200 142912 56980 43919 0.7549290 8.995989e-04 0.2808297408 1.190331e-03
Fully vaccinated 300 115890 68669 58975 0.6903637 1.001936e-03 0.3701727153 1.449928e-03
Fully vaccinated 400 19854 102527 121083 0.2770401 1.545579e-03 1.2740463692 5.522468e-03
Fully vaccinated 500 14892 106903 121599 0.2149698 1.456927e-03 1.5271294668 6.726195e-03
Fully vaccinated 600 12969 108770 121623 0.1879263 1.401650e-03 1.6614390472 7.410710e-03
Fully vaccinated 0 754136 108872 121682 0.9998647 1.339125e-05 0.0001352541 1.339215e-05
Fully vaccinated 1 753975 108966 121718 0.9997401 1.856257e-05 0.0002599267 1.856619e-05
Fully vaccinated 100 742497 116168 126070 0.9901658 1.137731e-04 0.0098824030 1.148972e-04
Fully vaccinated 200 305723 207300 475391 0.8379134 4.877229e-04 0.1766507627 5.814014e-04
Fully vaccinated 300 164239 226741 594210 0.7657226 6.716804e-04 0.2666992314 8.765044e-04
Fully vaccinated 400 94417 238081 654035 0.7074183 8.167861e-04 0.3458637298 1.153882e-03
Fully vaccinated 500 19094 243257 722253 0.6175555 1.472519e-03 0.4816156155 2.382630e-03
Fully vaccinated 600 1132 244742 738683 0.4844882 4.688299e-03 0.7238974867 9.657122e-03
Variable Beta (SE) HR (95% CI) P
fully_vaccinated_bl_bisTRUE -0.61 (0.01) 0.54 (0.54, 0.55) <0.001
sex_cd
     1 (ref)
     2 0.11 (0.00) 1.12 (1.11, 1.13) <0.001
age_cd
     2 (ref)
     3 -0.07 (0.01) 0.93 (0.91, 0.95) <0.001
     4 0.02 (0.01) 1.02 (1.00, 1.04) 0.05
     5 0.13 (0.01) 1.14 (1.11, 1.16) <0.001
     6 0.22 (0.01) 1.24 (1.22, 1.27) <0.001
     7 0.27 (0.01) 1.31 (1.28, 1.34) <0.001
     8 0.31 (0.01) 1.36 (1.33, 1.39) <0.001
     9 0.21 (0.01) 1.24 (1.21, 1.26) <0.001
     10 0.04 (0.01) 1.04 (1.02, 1.06) <0.001
     11 -0.15 (0.01) 0.86 (0.84, 0.88) <0.001
     12 -0.38 (0.01) 0.68 (0.67, 0.70) <0.001
     13 -0.56 (0.02) 0.57 (0.55, 0.59) <0.001
     14 -0.86 (0.02) 0.42 (0.41, 0.43) <0.001
     15 -1.25 (0.02) 0.29 (0.28, 0.30) <0.001
     16 -1.31 (0.02) 0.27 (0.26, 0.28) <0.001
     17 -1.36 (0.02) 0.26 (0.24, 0.27) <0.001
     18 -1.11 (0.02) 0.33 (0.32, 0.34) <0.001
residence_area_cd
     ES241 (ref)
     ES242 -0.10 (0.01) 0.91 (0.89, 0.92) <0.001
     ES243 -0.02 (0.01) 0.98 (0.97, 0.99) <0.001
pregnancy_blTRUE 0.13 (0.01) 1.14 (1.12, 1.17) <0.001
essential_worker_blTRUE 0.52 (0.02) 1.68 (1.62, 1.75) <0.001
institutionalized_blTRUE 0.32 (0.03) 1.38 (1.31, 1.46) <0.001
foreign_blTRUE -0.48 (0.01) 0.62 (0.61, 0.62) <0.001
comorbidities_blTRUE 0.07 (0.01) 1.07 (1.06, 1.08) <0.001
immunestatus_blTRUE 0.06 (0.02) 1.07 (1.03, 1.10) <0.001