Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records

Figures & data

Figure 1. Main covariates and study period analysis timeline with risk period scenarios.

Table 1. Summary statistics of the study subjects.

	SARS-CoV-2 vaccinated (first dose)				SARS-CoV-2 infected
Characteristics	No^1		Yes^1	p-Value^2	No^1	Yes^1	p-Value^2
Person years of follow-up	2,080,817		1,125,663		3,005,364	201,116
Age (in years)	41 (29, 53)		69 (56, 76)	<0.001	50 (33, 65)	45 (30, 58)	<0.001
Age group				<0.001			<0.001
17–30	502,695 (19%)		50,086 (1.9%)		509,567 (19%)	43,214 (1.6%)
31–44	483,121 (18%)		75,451 (2.9%)		519,692 (20%)	38,880 (1.5%)
45–64	653,129 (25%)		211,705 (8.0%)		810,064 (31%)	54,770 (2.1%)
65+	94,198 (3.6%)		573,314 (22%)		638,514 (24%)	28,998 (1.1%)
Sex				<0.001			<0.001
Female	797,261 (30%)		533,658 (20%)		1,238,305 (47%)	92,614 (3.5%)
Male	935,882 (35%)		376,898 (14%)		1,239,532 (47%)	73,248 (2.8%)
Deprivation quintile				<0.001			<0.001
5. Least deprived	301,992 (11%)		192,030 (7.3%)		464,790 (18%)	29,232 (1.1%)
4	303,841 (11%)		186,612 (7.1%)		464,323 (18%)	26,130 (1.0%)
3	317,679 (12%)		176,172 (6.7%)		466,146 (18%)	27,705 (1.0%)
2	323,068 (12%)		164,375 (6.2%)		452,484 (17%)	34,959 (1.3%)
1. Most deprived	341,094 (13%)		140,336 (5.3%)		445,297 (17%)	36,133 (1.4%)
Unknown	145,469 (5.5%)		51,031 (1.9%)		184,797 (7.0%)	11,703 (0.4%)
Ethnicity				<0.001			<0.001
White	1,457,581 (55%)		851,375 (32%)		2,158,716 (82%)	150,240 (5.7%)
Black/Black British	12,381 (0.5%)		2,473 (<0.1%)		13,768 (0.5%)	1,086 (<0.1%)
Asian/Asian British	44,477 (1.7%)		11,759 (0.4%)		51,332 (1.9%)	4,904 (0.2%)
Mixed	31,058 (1.2%)		6,301 (0.2%)		34,207 (1.3%)	3,152 (0.1%)
Other	11,721 (0.4%)		1,573 (<0.1%)		12,449 (0.5%)	845 (<0.1%)
Unknown	175,925 (6.7%)		37,075 (1.4%)		207,365 (7.8%)	5,635 (0.2%)
Name of vaccine				<0.001			<0.001
Unvaccinated	1,733,143 (66%)		0 (0%)		1,623,135 (61%)	110,008 (4.2%)
Pfizer-BioNTech (BNT162b2)	0 (0%)		426,648 (16%)		393,540 (15%)	33,108 (1.3%)
Oxford-ChAdOx1 (ChAdOx1)	0 (0%)		483,908 (18%)		461,162 (17%)	22,746 (0.9%)
No. of risk factor				<0.001			<0.001
0	1,128,361 (43%)		413,871 (16%)		1,451,164 (55%)	91,068 (3.4%)
1	404,873 (15%)		228,625 (8.6%)		592,092 (22%)	41,406 (1.6%)
2+	199,909 (7.6%)		268,060 (10%)		434,581 (16%)	33,388 (1.3%)
Vaccination & infection^a	0 (0%)		6,558 (0.2%)	<0.001	0 (0%)	6,558 (0.2%)	<0.001
COVID-19 episodes				<0.001			<0.001
0 episode	1,623,135 (61%)		854,702 (32%)		2,477,837 (94%)	0 (0%)
1 episode	109,776 (4.2%)		55,338 (2.1%)		0 (0%)	165,114 (6.2%)
2+ episodes	232 (<0.1%)		516 (<0.1%)		0 (0%)	748 (<0.1%)
CVST outcome	694 (<0.1%)		683 (<0.1%)	<0.001	1,100 (<0.1%)	277 (<0.1%)	<0.001
Died during the study	44,294 (1.7%)		5,508 (0.2%)	<0.001	40,986 (1.6%)	8,816 (0.3%)	<0.001
^1Median (IQR) for continuous variables or frequency (%) for categorical variables.
^2Wilcoxon rank sum test; Pearson’s Chi-squared test. ^a Exposed to both the vaccine and infection within 28 d of each other.
Incident CVST by type of exposures
		SARS-CoV-2 vaccinated*			SARS-CoV-2 infected
Characteristic		Yes, N = 1,3721			Yes, N = 1,3721
Outcome period
Before exposure		1,261 (92%)			1,286 (94%)
1–28 d post exposure		52 (3.8%)			48 (3.5%)
29+ d post exposure		59 (4.3%)			38 (2.8%)

¹n (%), * first dose.

Figure 2. Cox regression estimates of CVST events following SARS-CoV-2 vaccination: all participants.

Table 2. Cox regression estimates of CVST events following SARS-CoV-2 vaccination by vaccine type.

	HR (adjusted): Pfizer-BioNTech (BNT162b2)			HR (adjusted): Oxford-ChAdOx1 (ChAdOx1)
Characteristics	HR	95% CI	p-Value	HR	95% CI	p-Value
Outcome period			0.10			0.070
Before exposure	1 (ref)	1 (ref)		1 (ref)	1 (ref)
1–28 d post exposure	1.18	0.63, 2.21		1.40	0.95, 2.05
Age group			<0.001			<0.001
<50 y	1 (ref)	1 (ref)		1 (ref)	1 (ref)
50+ y	5.79	4.84, 6.92		5.74	4.81, 6.84
Sex			<0.001			<0.001
Female	1 (ref)	1 (ref)		1 (ref)	1 (ref)
Male	1.60	1.40, 1.83		1.63	1.45, 1.83
Vaccination & infection			<0.001			<0.001
Unvaccinated	1 (ref)	1 (ref)		1 (ref)	1 (ref)
No	0.43	0.36, 0.52		0.67	0.59, 0.77
Yes	1.04	0.33, 3.25		1.77	0.84, 3.73
Comorbidity			<0.001			<0.001
0	1 (ref)	1 (ref)		1 (ref)	1 (ref)
1	2.35	1.91, 2.88		2.08	1.73, 2.50
2+	9.52	8.02, 11.3		7.38	6.33, 8.60
Deprivation quintile			0.001			<0.001
5. Least deprived	1 (ref)	1 (ref)		1 (ref)	1 (ref)
4	0.86	0.68, 1.09		0.96	0.79, 1.18
3	0.96	0.77, 1.21		1.08	0.89, 1.31
2	0.98	0.79, 1.23		1.04	0.86, 1.27
1. Most deprived	1.32	1.07, 1.62		1.47	1.23, 1.77
Unknown	0.85	0.61, 1.19		1.04	0.78, 1.38
Ethnicity			<0.001			<0.001
White	1 (ref)	1 (ref)		1 (ref)	1 (ref)
Black/Black British	0.68	0.22, 2.12		0.81	0.30, 2.17
Asian/Asian British	0.65	0.34, 1.26		0.63	0.34, 1.18
Mixed	1.41	0.85, 2.36		1.14	0.67, 1.93
Other	0.93	0.30, 2.89		0.84	0.27, 2.62
Unknown	0.42	0.28, 0.63		0.45	0.31, 0.64

HR: hazard Ratio; CI: confidence interval.

Figure 3. Cox regression estimates of CVST events following SARS-CoV-2 infection: all participants.

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):1–11. doi:10.1056/NEJMoa2034577.

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