Enhanced passive safety surveillance of high-dose and standard-dose quadrivalent inactivated split-virion influenza vaccines in Germany and Finland during the 2022/23 influenza season

Figures & data

Table 1. Overview of AEFI reporting in Germany (HD-IIV4) and Finland (SD-IIV4) in 2022/23 influenza season.

	Vaccinees reporting ≥ 1 suspected AEFI, n	Number of AEFI	Vaccinee RR
HD-IIV4 in Germany, VCs distributed, n = 1041
AEFI ≤7 d of vaccination	6	15^a	0.58 (0.21, 1.25)
AEFI during the entire follow-up period^b	10	31	0.96 (0.46, 1.76)
By intensity^c
Mild	3	3	0.29 (0.06, 0.84)
Moderate	4	12	0.38 (0.10, 0.98)
Severe	0	0	0.00 (0.00, 0.35)
Serious AEFI	1	1	0.10 (0.00, 0.53)
SD-IIV4 in Finland, VCs distributed, n = 1001
AEFI ≤7 d of vaccination	48	133^d	4.80 (3.56, 6.31)
AEFI during the entire follow-up period^e	51	142	5.09 (3.82, 6.64)
By intensity^f
Mild	39	80	3.90 (2.78, 5.29)
Moderate	25	49	2.50 (1.62, 3.66)
Severe	2	5	0.20 (0.02, 0.72)
Serious AEFI	0	0	0.00 (0.00, 0.37)

AEFI, adverse event following immunization; AEI, adverse events of interest; HD, high-dose; IIV4, quadrivalent inactivated split-virion influenza vaccine; SD, standard dose; RR, reporting rate, VC, vaccination card.

^aA total of seven AEFI occurred on the same day or the following day after vaccination; four AEFI occurred 2 d post-vaccination, and four AEFI occurred within 3–4 d post-vaccination.

^bThe time to onset was known for 16/31 AEFI.

^cFour vaccinees reported 16 AEFI of unknown intensity (RR 0.38 [0.10, 0.98]).

^dA total of 117 AEFI occurred on the same day or the following day after vaccination, nine AEFI occurred 2 d post-vaccination and seven AEFI occurred within 4 d post-vaccination.

^eEight vaccinees reported eight AEFI of unknown intensity (RR0.80 [0.35, 1.57]).

^fThe time to onset was known for 133/142 AEFI.

Table 2. Reporting of AEIs by SOC in Germany (HD-IIV4) in 2022/23 influenza season.

	VCs distributed, n = 1041
	≤7 d post-vaccination^a			During entire follow-up period^a
	n	nAEI	Vaccinee RR (95% CI)	n	nAEI	Vaccinee RR (95% CI)
Any AEI	6	12^b	0.58 (0.21, 1.25)	10	22	0.96 (0.46, 1.76)
Injection site reaction	5	7	0.48 (0.16, 1.12)	8	10	0.77 (0.33, 1.51)
Headache	1	1	0.10 (0.00, 0.53)	1	1	0.10 (0.00, 0.53)
Myalgia	1	1	0.10 (0.00, 0.53)	3	4	0.29 (0.06, 0.84)
Fever	0	0	0.00 (0.00, 0.35)	2	2	0.19 (0.02, 0.69)
Malaise	1	1	0.10 (0.00, 0.53)	2	3	0.19 (0.02, 0.69)
Arthralgia	0	0	0.00 (0.00, 0.35)	0	0	0.00 (0.00, 0.35)
Nausea	1	1	0.10 (0.00, 0.53)	1	1	0.10 (0.00, 0.53)
Decreased appetite	0	0	0.00 (0.00, 0.35)	0	0	0.00 (0.00, 0.35)
Events indicative of allergic and hypersensitivity reactions^c	1	1	0.10 (0.00, 0.53)	1	1	0.10 (0.00, 0.53)

AEI, adverse events of interest; CI, confidence interval; HD, high-dose; IIV4, quadrivalent inactivated split-virion influenza vaccine; SD, standard dose; n, number of vaccinees; nAEI, number of AEIs; RR, reporting rate; SOC, system organ class; VC, vaccination card.

^aThe time to onset was known for 13/22 AEIs; 1 AEI of injection site reaction was reported >7 d after vaccination.

^bA total of seven AEIs occurred on the same day or the following day after vaccination; four AEIs occurred within 2 d post-vaccination and one AEI occurred 4 d post-vaccination.

^cIncluding rash and ocular symptoms.

Table 3. Reporting of ‘other’ AEFI by PT in Germany (HD-IIV4) in 2022/23 influenza season.

	VC distributed n = 1041
	≤7 d post-vaccination^a			During entire follow-up period^a
	n	nAEFI	Vaccinee RR (95% CI)	n	nAEFI	Vaccinee RR (95% CI)
‘Other’ AEFI	2	3^b	0.19 (0.02, 0.69)	5	9	0.48 (0.16, 1.12)
Nasopharyngitis	2	2	0.19 (0.02, 0.69)	2	2	0.19 (0.02, 0.69)
Cough	1	1	0.10 (0.00, 0.53)	1	1	0.10 (0.00, 0.53)
Chills	0	0	0.00 (0.00, 0.35)	3	3	0.29 (0.06, 0.84)
Dyspnoea	0	0	0.00 (0.00, 0.35)	1	1	0.10 (0.00, 0.53)
Angina pectoris	0	0	0.00 (0.00, 0.35)	1	1	0.10 (0.00, 0.53)
Listless	0	0	0.00 (0.00, 0.35)	1	1	0.10 (0.00, 0.53)

AEFI, adverse event following immunization; CI, confidence interval; HD, high-dose; IIV4, quadrivalent inactivated split-virion influenza vaccine; n, number of vaccinees; nAEFI, number of AEFI; PT, preferred Term; RR, reporting rate; VC, vaccination card.

^aThe time to onset was known for 3/9 ‘other’ AEFI.

^bAll three AEFI occurred within 3–4 d post-vaccination.

As per protocol, the calculation of time to onset relies on the vaccination date recorded in the VC. However, a subject reporting an AEFI of angina pectoris by telephone did not provide the VC number, hindering the link to VC data and resulting in the event being classified as “unknown time to onset.” Nevertheless, based on details in the case narrative, the event occurred 6 hours post-vaccination with HD-IIV4.

Table 4. Reporting of AEIs by SOC in Finland (SD-IIV4) in 2022/23 influenza season.

	VCs distributed, n = 1001
	≤7 d post-vaccination^a			During entire follow-up period^a
	n	nAEI	Vaccinee RR (95% CI)	n	nAEI	Vaccinee RR (95% CI)
Any AEI	47	114^b	4.70 (3.47, 6.20)	50	123	5.00 (3.73, 6.53)
Injection site reaction	36	56	3.60 (2.53, 4.94)	39	62	3.90 (2.78, 5.29)
Headache	13	13	1.30 (0.69, 2.21)	13	13	1.30 (0.69, 2.21)
Myalgia	15	15	1.50 (0.84, 2.46)	16	16	1.60 (0.92, 2.58)
Fever	8	8	0.80 (0.35, 1.57)	8	8	0.80 (0.35, 1.57)
Malaise	6	6	0.60 (0.22, 1.30)	6	6	0.60 (0.22, 1.30)
Arthralgia	5	5	0.50 (0.16, 1.16)	5	5	0.50 (0.16, 1.16)
Nausea	4	4	0.40 (0.11, 1.02)	5	5	0.50 (0.16, 1.16)
Decreased appetite	2	2	0.20 (0.02, 0.72)	2	2	0.20 (0.02, 0.72)
Events indicative of allergic and hypersensitivity reactions^c	3	5	0.30 (0.06, 0.87)	4	6	0.40 (0.11, 1.02)

AEI, adverse events of interest; CI, confidence interval; HD, high-dose; IIV4, quadrivalent inactivated split-virion influenza vaccine; SD, standard dose; n, number of vaccinees; nAEI, number of AEIs; RR, reporting rate; SOC, system organ class; VC, vaccination card.

^aThe time to onset was known for 114/123 AEIs.

^bA total of 102 AEIs occurred on the same day or the following day after vaccination and 12 AEIs occurred within 4 d of vaccination.

^cIncluding rash and ocular symptoms.

Table 5. Reporting of ‘other’ AEFI by PT in Finland (SD-IIV4) in 2022/23 influenza season.

	VCs distributed, n = 1001 ≤7 d of vaccination^a
	n	nAEFI^a	Vaccinee RR (95% CI)
‘Other’ AEFI	13	19^b	1.30 (0.69, 2.21)
Nasopharyngitis	4	4	0.40 (0.11, 1.02)
Influenza	2	2	0.20 (0.02, 0.72)
Feeling cold	4	4	0.40 (0.11, 1.02)
Lymph node pain	1	1	0.10 (0.00, 0.56)
Lymphadenopathy	1	1	0.10 (0.00, 0.56)
Diarrhoea	1	1	0.10 (0.00, 0.56)
Toothache	1	1	0.10 (0.00, 0.56)
Oropharyngeal pain	1	1	0.10 (0.00, 0.56)
Sneezing	1	1	0.10 (0.00, 0.56)
Blood urine present	1	1	0.10 (0.00, 0.56)
Body temperature decreased	1	1	0.10 (0.00, 0.56)
Back pain	1	1	0.10 (0.00, 0.56)
Insomnia	1	1	0.10 (0.00, 0.56)

AEFI, adverse event following immunization; CI, confidence interval; IIV4, quadrivalent inactivated split-virion influenza vaccine; n, number of vaccinees; nAEFI, number of AEFI; PT, preferred Term; RR, reporting rate; SD, standard dose; VC, vaccination card.

^aThe time to onset was known for all ‘other’ AEFI and all occurred ≤7 d after vaccination.

^bA total of 15 AEFI occurred on the same day or the following day after vaccination and 4 AEFI occurred within 4 d post-vaccination.

Data availability statement

The datasets generated and/or analyzed during the current study, including the raw data, are not publicly available in order to safeguard the privacy of participants and the confidentiality and protection of their data, as well as protect commercially sensitive information. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of our trial participants. Further details on Sanofi’s data sharing criteria, including required permissions to access the data, eligible studies, and process for requesting access can be found at: https://www.vivli.org/.