Risk of herpes zoster following mRNA COVID-19 vaccine administration

Figures & data

Figure 1. Flowchart for Mrna-1273- and BNT162b2-vaccinated cohorts, and for their unvaccinated matches.

Table 1. Baseline characteristics of Mrna-1273- and BNT162b2-vaccinated^a and unvaccinated cohorts, 12/14/2020–05/31/2021 (N = 3,128,157).

	mRNA-1273-vaccinated	BNT162b2-vaccinated	Unvaccinated
	N = 1,052,362	N = 1,055,461	N = 1,020,334
Characteristic	n (%)
Age at index date^b, years
16–34	211912 (20.1)	290712 (27.5)	420933 (41.3)
35–49	239360 (22.7)	260945 (24.7)	275041 (27)
50–64	292754 (27.8)	258921 (24.5)	217591 (21.3)
65+	308336 (29.3)	244883 (23.2)	106769 (10.5)
Sex
Female	564802 (53.7)	577102 (54.7)	534339 (52.4)
Male	487560 (46.3)	478359 (45.3)	485995 (47.6)
Race/Ethnicity
Non-Hispanic White	360986 (34.3)	337798 (32.0)	329680 (32.3)
Non-Hispanic Black	75326 (7.2)	66280 (6.3)	109125 (10.7)
Hispanic	397787 (37.8)	408455 (38.7)	449844 (44.1)
Non-Hispanic Asian	142960 (13.6)	156631 (14.8)	55721 (5.5)
Other^c	75303 (7.2)	86297 (8.2)	75964 (7.4)
Index date
December 2020	19818 (1.9)	52193 (4.9)	42005 (4.1)
January 2021	191666 (18.2)	130333 (12.3)	124429 (12.2)
February 2021	186885 (17.8)	221212 (21.0)	136094 (13.3)
March 2021	354037 (33.6)	300047 (28.4)	375722 (36.8)
April 2021	238021 (22.6)	254615 (24.1)	251903 (24.7)
May 2021	61935 (5.9)	97061 (9.2)	90181 (8.8)
History of ZVL vaccination^d
No	915772 (87.0)	945147 (89.5)	990437 (97.1)
Yes, ≤5 years	22437 (2.1)	18069 (1.7)	5923 (0.6)
Yes, >5 years	114153 (10.8)	92245 (8.7)	23974 (2.3)
History of RZV vaccination^e
No	953604 (90.6)	972815 (92.2)	999903 (98.0)
Yes	98758 (9.4)	82646 (7.8)	20431 (2.0)
History of HZ^f
No	980702 (93.2)	993724 (94.2)	979646 (96.0)
Yes	71660 (6.8)	61737 (5.8)	40688 (4.0)
Immunocompromised statusg
No	1020783 (97.0)	1028977 (97.5)	1001977 (98.2)
Yes	31579 (3.0)	26484 (2.5)	18357 (1.8)
History of SARS-CoV-2 infectionh
No	952560 (90.5)	959361 (90.9)	887040 (86.9)
Yes	99802 (9.5)	96100 (9.1)	133294 (13.1)
Chronic diseasesi
Kidney disease	48757 (4.6)	35967 (3.4)	16996 (1.7)
Heart disease	285372 (27.1)	230662 (21.9)	132460 (13.0)
Lung disease	60746 (5.8)	52696 (5.0)	41074 (4.0)
Liver disease	22334 (2.1)	18338 (1.7)	13785 (1.4)
Diabetes	136639 (13.0)	104651 (9.9)	59096 (5.8)
Number of outpatient visits^i
0–4	597908 (56.8)	652318 (61.8)	705044 (69.1)
5–10	267069 (25.4)	246076 (23.3)	198512 (19.5)
≥11	187385 (17.8)	157067 (14.9)	116778 (11.4)
Number of emergency department visits^i
0	912897 (86.7)	925499 (87.7)	867645 (85.0)
1	98148 (9.3)	92490 (8.8)	104856 (10.3)
≥2	41317 (3.9)	37472 (3.6)	47833 (4.7)
Number of hospitalization^i
0	964804 (91.7)	969071 (91.8)	936969 (91.8)
1	59844 (5.7)	58707 (5.6)	59299 (5.8)
≥2	27714 (2.6)	27683 (2.6)	24066 (2.4)
Number of virtual encounters^i,j
0–10	954591 (90.7)	970159 (91.9)	949517 (93.1)
11–20	70051 (6.7)	60920 (5.8)	51336 (5.0)
≥21	27720 (2.6)	24382 (2.3)	19481 (1.9)

Note: ^aThe study included KPSC members aged ≥16 years who received at least one dose of COVID-19 vaccine by 05/31/2021 with two doses >14 days apart.

^bThe index date was the date of the first dose of COVID-19 vaccine for vaccinated individuals; the same date was used for their matched unvaccinated counterparts.

^cIncludes other, multiple, or unknown race/ethnicity.

^dDefined prior to index date.

^eDefined between 04/01/2018 and index date.

^fDefined prior to 6 months before the index date.

^gDefined as HIV, leukemia, lymphoma, congenital immunodeficiencies, asplenia/hyposplenia, and transplant (including heart, kidney, liver, lung, pancreas, and bone marrow) prior to index date, or receipt of non-steroidal immunosuppressing medications overlapping with index date.

^hDefined between 03/01/2020 and index date.

ⁱDefined in one year prior to index date.

^jVirtual encounters included e-mail, e-visit, telephone appointment visit, and video.

Abbreviations: COVID-19, coronavirus disease 2019; HZ, herpes zoster; KPSC, Kaiser Permanente Southern California; RZV, recombinant zoster vaccine; ZVL, zoster vaccine live.

Table 2. Hazard ratio of herpes zoster up to 90 days after the first dose of mRNA COVID-19 vaccination, overall and by age group.

			Hazard Ratio (95% CI)^b
	Number of HZ cases^a	N^a	Unadjusted	Adjusted^c
All
mRNA-1273	529 vs. 942	1052362 vs. 1020334	1.45 (1.28–1.65)	1.08 (0.95–1.23)
BNT162b2	344 vs. 942	1055461 vs. 1020334	1.22 (1.06–1.41)	1.01 (0.87–1.17)
Age at index date, years
16–34
mRNA-1273	38 vs. 147	211912 vs. 420933	1.28 (0.86–1.90)	1.19 (0.80–1.77)
BNT162b2	41 vs. 147	290712 vs. 420933	1.31 (0.88–1.93)	1.25 (0.84–1.87)
35–49
mRNA-1273	86 vs. 278	239360 vs. 275041	1.03 (0.78–1.35)	0.96 (0.73–1.28)
BNT162b2	73 vs. 278	260945 vs. 275041	1.05 (0.78–1.42)	0.99 (0.73–1.34)
50–64
mRNA-1273	178 vs. 316	292754 vs. 217591	1.15 (0.92–1.43)	1.13 (0.91–1.41)
BNT162b2	118 vs. 316	258921 vs. 217591	1.11 (0.87–1.43)	1.11 (0.87–1.43)
65+
mRNA-1273	227 vs. 201	308336 vs. 106769	0.99 (0.78–1.26)	1.04 (0.82–1.32)
BNT162b2	112 vs. 201	244883 vs. 106769	0.80 (0.61–1.06)	0.85 (0.64–1.12)

^amRNA-1273/BNT162b2 vs. unvaccinated.

^bReference group: unvaccinated.

^cCox proportional hazard model for HZ comparing individuals with and without mRNA COVID-19 vaccine, adjusted for all other variables in Table 1 except for age in age-stratified analyses.

Abbreviations: COVID-19, coronavirus disease 2019; HZ, herpes zoster.

Table 3. Hazard ratio of herpes zoster up to 90 days after the second dose of mRNA COVID-19 vaccination, overall and by age group.

			Hazard Ratio (95% CI)^b
	Number of HZ cases^a	N^a	Unadjusted	Adjusted^c
All
mRNA-1273	1484 vs. 942	959310 vs. 1020334	1.59 (1.46–1.72)	1.14 (1.05–1.24)
BNT162b2	1313 vs. 942	960843 vs. 1020334	1.40 (1.29–1.52)	1.12 (1.03–1.22)
Age at index date, years
16–34
mRNA-1273	90 vs. 147	179359 vs. 420933	1.38 (1.06–1.80)	1.31 (1.01–1.72)
BNT162b2	102 vs. 147	248722 vs. 420933	1.13 (0.88–1.45)	1.12 (0.87–1.45)
35–49
mRNA-1273	251 vs. 278	213548 vs. 275041	1.11 (0.93–1.31)	1.07 (0.90–1.27)
BNT162b2	275 vs. 278	236321 vs. 275041	1.10 (0.93–1.30)	1.07 (0.91–1.27)
50–64
mRNA-1273	498 vs. 316	269110 vs. 217591	1.18 (1.03–1.36)	1.17 (1.02–1.35)
BNT162b2	404 vs. 316	239539 vs. 217591	1.08 (0.93–1.25)	1.08 (0.93–1.25)
65+
mRNA-1273	645 vs. 201	297293 vs. 106769	1.08 (0.92–1.27)	1.14 (0.97–1.34)
BNT162b2	532 vs. 201	236261 vs. 106769	1.12 (0.95–1.32)	1.20 (1.02–1.42)

Note: ^amRNA-1273/BNT162b2 vs. unvaccinated.

^bReference group: unvaccinated.

^cCox proportional hazard model for HZ comparing individuals with and without mRNA COVID-19 vaccine, adjusted for all other variables in Table 1 except for age in age-stratified analyses.

Abbreviations: COVID-19, coronavirus disease 2019; HZ, herpes zoster.

Table 4. Hazard ratio of herpes zoster up to 90 days after the second dose of mRNA COVID-19 vaccination in individuals aged ≥50 years, by RZV or ZVL vaccination status.

			Hazard Ratio (95% CI)^b
	Number of HZ cases^a	N^a	Unadjusted	Adjusted^c
RZV or ZVL vaccinated
mRNA-1273	256 vs. 55	186274 vs. 44831	1.02 (0.76–1.37)	0.97 (0.72–1.30)
BNT162b2	217 vs. 55	152623 vs. 44831	1.06 (0.79–1.42)	1.03 (0.76–1.39)
RZV and ZVL unvaccinated
mRNA-1273	887 vs.462	380014 vs. 279529	1.32 (1.18–1.48)	1.18 (1.06–1.33)
BNT162b2	717 vs. 462	323064 vs. 279529	1.25 (1.12–1.41)	1.15 (1.02–1.29)

Note: ^amRNA-1273/BNT162b2 vs. unvaccinated.

^bReference group: unvaccinated.

^cCox proportional hazard model for HZ comparing individuals with and without mRNA COVID-19 vaccine, adjusted for all other variables in Table 1 except for RZV or ZVL vaccination status.

Abbreviations: COVID-19, coronavirus disease 2019; HZ, herpes zoster; RZV, recombinant zoster vaccine; ZVL, zoster vaccine live.