## 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 (treated/exposed) is matched to an individual who has not (yet) completed the primary vaccination schedule (control).
- 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 | 2020-03-05 - 2022-05-20
Enrollment period | 2021-01-01 - 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
| Intervention group (Completed a primary vaccination schedule) (N=8378) | Control group (Not completed a primary vaccination schedule) (N=949) | P-value
--- | --- | --- | ---
ᵃ5-year age groups
sex_cd |  |  |
Mean (SD) | 1.47 (0.537) | 1.48 (0.541) | 0.356
Median [Min, Max] | 1.00 [0, 2.00] | 2.00 [0, 2.00] |
age_cdᵃ |  |  |
Mean (SD) | 11.6 (2.96) | 11.6 (3.00) | 0.914
Median [Min, Max] | 12.0 [2.00, 18.0] | 12.0 [2.00, 18.0] |
residence_area_cd |  |  |
731 | 1170 (14.0%) | 139 (14.6%) | 0.574
732 | 1182 (14.1%) | 123 (13.0%) |
733 | 6026 (71.9%) | 687 (72.4%) |
institutionalized_bl |  |  |
Yes | 233 (2.8%) | 28 (3.0%) | 0.845
No | 8145 (97.2%) | 921 (97.0%) |
foreign_bl |  |  |
Yes | 1271 (15.2%) | 123 (13.0%) | 0.0782
No | 7107 (84.8%) | 826 (87.0%) |
pregnancy_bl |  |  |
Yes | 99 (1.2%) | 20 (2.1%) | 0.0241
No | 8279 (98.8%) | 929 (97.9%) |
essential_worker_bl |  |  |
Yes | 231 (2.8%) | 27 (2.8%) | 0.959
No | 8147 (97.2%) | 922 (97.2%) |
comorbidities_bl |  |  |
Yes | 3852 (46.0%) | 451 (47.5%) | 0.384
No | 4526 (54.0%) | 498 (52.5%) |
immunestatus_bl |  |  |
Yes | 2349 (28.0%) | 250 (26.3%) | 0.287
No | 6029 (72.0%) | 699 (73.7%) |

Table 1
| Intervention group (Completed a primary vaccination schedule) (N=8126) | Control group (Not completed a primary vaccination schedule) (N=8126) | P-value
--- | --- | --- | ---
ᵃ5-year age groups
sex_cd |  |  |
Mean (SD) | 1.46 (0.537) | 1.45 (0.549) | 0.179
Median [Min, Max] | 1.00 [0, 2.00] | 1.00 [0, 2.00] |
age_cdᵃ |  |  |
Mean (SD) | 11.6 (2.96) | 11.6 (2.99) | 0.607
Median [Min, Max] | 12.0 [2.00, 18.0] | 12.0 [2.00, 18.0] |
residence_area_cd |  |  |
731 | 1133 (13.9%) | 1170 (14.4%) | 0.00891
732 | 1144 (14.1%) | 1012 (12.5%) |
733 | 5849 (72.0%) | 5944 (73.1%) |
institutionalized_bl |  |  |
Yes | 225 (2.8%) | 217 (2.7%) | 0.736
No | 7901 (97.2%) | 7909 (97.3%) |
foreign_bl |  |  |
Yes | 1234 (15.2%) | 1232 (15.2%) | 0.983
No | 6892 (84.8%) | 6894 (84.8%) |
pregnancy_bl |  |  |
Yes | 97 (1.2%) | 83 (1.0%) | 0.33
No | 8029 (98.8%) | 8043 (99.0%) |
essential_worker_bl |  |  |
Yes | 226 (2.8%) | 224 (2.8%) | 0.962
No | 7900 (97.2%) | 7902 (97.2%) |
comorbidities_bl |  |  |
Yes | 3736 (46.0%) | 3721 (45.8%) | 0.826
No | 4390 (54.0%) | 4405 (54.2%) |
immunestatus_bl |  |  |
Yes | 2280 (28.1%) | 2287 (28.1%) | 0.917
No | 5846 (71.9%) | 5839 (71.9%) |

## Two-by-two tables

The individuals in the imported dataset are counted by ‘fully_vaccinated_bl’ and ‘confirmed_case_bl’.

| Confirmed case | Not confirmed case | Total
--- | --- | --- | ---
Completed a primary vaccination schedule | 2990 | 6010 | 9000
Not completed a primary vaccination schedule | 361 | 639 | 1000
Total | 3351 | 6649 | 10000

Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 0.9202832

The individuals eligible for analysis are counted by ‘fully_vaccinated_bl’ and ‘confirmed_case_bl’.

| Confirmed case | Not confirmed case | Total
--- | --- | --- | ---
Completed a primary vaccination schedule | 2639 | 5739 | 8378
Not completed a primary vaccination schedule | 329 | 620 | 949
Total | 2968 | 6359 | 9327

Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 0.9085929

The matched individuals are counted by ‘fully_vaccinated_bl’ and ‘confirmed_case_bl’.

| Confirmed case | Not confirmed case | Total
--- | --- | --- | ---
Completed a primary vaccination schedule | 2617 | 5715 | 8332
Not completed a primary vaccination schedule | 242 | 560 | 802
Total | 2859 | 6275 | 9134

Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 1.0409107

## Survival in un-matched population

Variable | Beta (SE) | HR (95% CI) | P
--- | --- | --- | ---
fully_vaccinated_blTRUE | -0.02 (0.07) | 0.98 (0.86, 1.11) | 0.71

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
--- | --- | --- | --- | --- | --- | --- | --- | ---
Not fully vaccinated | 0 | 902 | 1 | 0 | 0.9988914 | 0.0011080327 | 0.0011086475 | 0.0011086475
Not fully vaccinated | 1 | 901 | 2 | 0 | 0.9977827 | 0.0015661251 | 0.0022185254 | 0.0015687346
Not fully vaccinated | 100 | 887 | 15 | 0 | 0.9833703 | 0.0042579213 | 0.0167601671 | 0.0043275070
Not fully vaccinated | 200 | 881 | 21 | 0 | 0.9767184 | 0.0050209720 | 0.0235436859 | 0.0051377719
Not fully vaccinated | 300 | 869 | 33 | 0 | 0.9634146 | 0.0062511087 | 0.0372477521 | 0.0064843714
Not fully vaccinated | 400 | 693 | 212 | 0 | 0.7649667 | 0.0141183086 | 0.2674750096 | 0.0184246060
Not fully vaccinated | 500 | 621 | 281 | 0 | 0.6884701 | 0.0154201697 | 0.3726241520 | 0.0223575550
Not fully vaccinated | 600 | 620 | 282 | 0 | 0.6873614 | 0.0154351407 | 0.3742344580 | 0.0224154712
Fully vaccinated | 0 | 8378 | 1 | 0 | 0.9998806 | 0.0001193531 | 0.0001193602 | 0.0001193602
Fully vaccinated | 1 | 8377 | 2 | 0 | 0.9997613 | 0.0001687807 | 0.0002387347 | 0.0001688109
Fully vaccinated | 100 | 8253 | 126 | 0 | 0.9849606 | 0.0013297021 | 0.0151514274 | 0.0013498093
Fully vaccinated | 200 | 3885 | 594 | 3997 | 0.9149921 | 0.0034433135 | 0.0887960657 | 0.0037611165
Fully vaccinated | 300 | 2645 | 1072 | 4665 | 0.7759389 | 0.0065510625 | 0.2534754869 | 0.0084351389
Fully vaccinated | 400 | 2307 | 1195 | 4885 | 0.7394797 | 0.0070201758 | 0.3015773379 | 0.0094855960
Fully vaccinated | 500 | 786 | 1200 | 6446 | 0.7378440 | 0.0070426699 | 0.3037910797 | 0.0095371385
Fully vaccinated | 600 | 7 | 1200 | 7171 | 0.7378440 | 0.0070426699 | 0.3037910797 | 0.0095371385

Variable | Beta (SE) | HR (95% CI) | P
--- | --- | --- | ---
fully_vaccinated_blTRUE | -0.02 (0.07) | 0.98 (0.86, 1.11) | 0.73
age_cd | 0.00 (0.01) | 1.00 (0.99, 1.02) | 0.64
sex_cd | -0.05 (0.05) | 0.95 (0.86, 1.04) | 0.26
residence_area_cd |  |  |
731 (ref) | – | – | –
732 | 0.04 (0.10) | 1.04 (0.85, 1.28) | 0.67
733 | 0.14 (0.08) | 1.15 (0.99, 1.34) | 0.07
essential_worker_blTRUE | 0.03 (0.15) | 1.03 (0.76, 1.39) | 0.84
institutionalized_blTRUE | 0.20 (0.14) | 1.22 (0.92, 1.61) | 0.17
foreign_blTRUE | -0.04 (0.07) | 0.96 (0.83, 1.11) | 0.60
comorbidities_blTRUE | 0.02 (0.05) | 1.02 (0.92, 1.13) | 0.75
immunestatus_blTRUE | 0.01 (0.06) | 1.01 (0.90, 1.13) | 0.93