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

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	2020-03-01 - 2023-05-09
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
	Intervention group (Completed a primary vaccination schedule) (N=923489)	Control group (Not completed a primary vaccination schedule) (N=84041)	P-value
ᵃ5-year age groups
sex_cd
Mean (SD)	1.51 (0.500)	1.48 (0.500)	<0.001
Median [Min, Max]	2.00 [1.00, 2.00]	1.00 [1.00, 2.00]
age_cdᵃ
Mean (SD)	10.5 (4.25)	6.12 (4.02)	<0.001
Median [Min, Max]	11.0 [2.00, 18.0]	5.00 [2.00, 18.0]
residence_area_cd
ES241	151519 (16.4%)	14698 (17.5%)	<0.001
ES242	90598 (9.8%)	7948 (9.5%)
ES243	681372 (73.8%)	61395 (73.1%)
institutionalized_bl
Yes	6899 (0.7%)	467 (0.6%)	<0.001
No	916590 (99.3%)	83574 (99.4%)
foreign_bl
Yes	118077 (12.8%)	18680 (22.2%)	<0.001
No	805412 (87.2%)	65361 (77.8%)
pregnancy_bl
Yes	18199 (2.0%)	2554 (3.0%)	<0.001
No	905290 (98.0%)	81487 (97.0%)
essential_worker_bl
Yes	5126 (0.6%)	508 (0.6%)	0.0696
No	918363 (99.4%)	83533 (99.4%)
comorbidities_bl
Yes	347000 (37.6%)	12462 (14.8%)	<0.001
No	576489 (62.4%)	71579 (85.2%)
immunestatus_bl
Yes	24296 (2.6%)	890 (1.1%)	<0.001
No	899193 (97.4%)	83151 (98.9%)

Table 1
	Intervention group (Completed a primary vaccination schedule) (N=761433)	Control group (Not completed a primary vaccination schedule) (N=761433)	P-value
ᵃ5-year age groups
sex_cd
Mean (SD)	1.52 (0.500)	1.52 (0.500)	0.999
Median [Min, Max]	2.00 [1.00, 2.00]	2.00 [1.00, 2.00]
age_cdᵃ
Mean (SD)	11.6 (3.58)	11.6 (3.58)	0.995
Median [Min, Max]	12.0 [3.00, 18.0]	12.0 [2.00, 18.0]
residence_area_cd
ES241	125375 (16.5%)	125408 (16.5%)	0.965
ES242	74726 (9.8%)	74629 (9.8%)
ES243	561332 (73.7%)	561396 (73.7%)
institutionalized_bl
Yes	6803 (0.9%)	6776 (0.9%)	0.823
No	754630 (99.1%)	754657 (99.1%)
foreign_bl
Yes	82139 (10.8%)	82128 (10.8%)	0.979
No	679294 (89.2%)	679305 (89.2%)
pregnancy_bl
Yes	12058 (1.6%)	12059 (1.6%)	1
No	749375 (98.4%)	749374 (98.4%)
essential_worker_bl
Yes	5012 (0.7%)	4990 (0.7%)	0.833
No	756421 (99.3%)	756443 (99.3%)
comorbidities_bl
Yes	330335 (43.4%)	330337 (43.4%)	0.999
No	431098 (56.6%)	431096 (56.6%)
immunestatus_bl
Yes	23137 (3.0%)	23126 (3.0%)	0.962
No	738296 (97.0%)	738307 (97.0%)

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	302871	729249	1032120
Not completed a primary vaccination schedule	70739	40946	111685
Total	373610	770195	1143805

Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 0.4633012

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	302485	621004	923489
Not completed a primary vaccination schedule	70702	13339	84041
Total	373187	634343	1007530

Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 0.3893423

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

	Confirmed case	Not confirmed case	Total
Completed a primary vaccination schedule	278204	543254	821458
Not completed a primary vaccination schedule	17969	6413	24382
Total	296173	549667	845840

Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 0.4595401

Survival in un-matched population

Variable	Beta (SE)	HR (95% CI)	P
fully_vaccinated_blTRUE	-1.04 (0.00)	0.35 (0.35, 0.36)	<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
Not fully vaccinated	0	84040	44	2	0.9994764	7.890901e-05	0.0005235602	7.892967e-05
Not fully vaccinated	1	83994	128	2	0.9984769	1.345224e-04	0.0015236316	1.346713e-04
Not fully vaccinated	100	72324	11434	328	0.8637700	1.184114e-03	0.1462861837	1.369364e-03
Not fully vaccinated	200	60640	23162	638	0.7231858	1.547247e-03	0.3236136856	2.136241e-03
Not fully vaccinated	300	52437	30908	709	0.6301512	1.670727e-03	0.4611073646	2.647294e-03
Not fully vaccinated	400	19231	64177	734	0.2301015	1.459079e-03	1.4584214966	6.283835e-03
Not fully vaccinated	500	14973	68358	746	0.1797946	1.331453e-03	1.7045512721	7.352075e-03
Not fully vaccinated	600	13068	70220	758	0.1573724	1.262740e-03	1.8376151146	7.973477e-03
Fully vaccinated	0	921548	135	93	0.9998535	1.260716e-05	0.0001464926	1.260808e-05
Fully vaccinated	1	921320	270	139	0.9997070	1.782880e-05	0.0002930215	1.783272e-05
Fully vaccinated	100	899217	16201	6679	0.9823522	1.374226e-04	0.0178033773	1.398757e-04
Fully vaccinated	200	391865	133323	400336	0.8289453	4.386578e-04	0.1874349466	5.286745e-04
Fully vaccinated	300	229835	156972	535570	0.7641409	5.751950e-04	0.2687999036	7.522163e-04
Fully vaccinated	400	96077	169266	658227	0.7114877	7.152373e-04	0.3401675691	1.004721e-03
Fully vaccinated	500	19495	174740	727389	0.6188334	1.432524e-03	0.4795834686	2.313120e-03
Fully vaccinated	600	1296	176278	744003	0.4863253	4.461938e-03	0.7201686300	9.157436e-03

Variable	Beta (SE)	HR (95% CI)	P
fully_vaccinated_blTRUE	-0.69 (0.01)	0.50 (0.50, 0.51)	<0.001
age_cd	-0.08 (0.00)	0.93 (0.93, 0.93)	<0.001
sex_cd	0.09 (0.00)	1.10 (1.09, 1.10)	<0.001
residence_area_cd
ES241 (ref)	–	–	–
ES242	-0.09 (0.01)	0.92 (0.90, 0.93)	<0.001
ES243	-0.01 (0.01)	0.99 (0.98, 1.00)	0.08
essential_worker_blTRUE	0.64 (0.02)	1.89 (1.82, 1.96)	<0.001
institutionalized_blTRUE	0.15 (0.03)	1.16 (1.10, 1.22)	<0.001
foreign_blTRUE	-0.28 (0.01)	0.76 (0.75, 0.77)	<0.001
comorbidities_blTRUE	-0.12 (0.01)	0.89 (0.88, 0.90)	<0.001
immunestatus_blTRUE	0.01 (0.02)	1.01 (0.98, 1.05)	0.38