Waning intra-season vaccine effectiveness against influenza A(H3N2) underlines the need for more durable protection

Figures & data

Table 1. Characteristics of the cases (N = 1633) and controls (N = 4857); Italy, 2018/2019 to 2022/2023.

Characteristic	Level	Cases, % (n)	Controls, % (n)	p-value
Sex (N = 6490)	Female	47.6 (778)	46.5 (2260)	0.45^a
	Male	52.4 (855)	53.5 (2597)
Age, years (N = 6490)	Median [IQR]	13 [4–59]	54 [9–75]	<0.001^b
	<15	51.5 (841)	29.4 (1426)	<0.001^a
	15–64	28.5 (465)	31.2 (1515)
	≥65	20.0 (327)	39.4 (1916)
Setting (N = 6490)	Outpatient	36.4 (594)	28.8 (1401)	<0.001^a
	Inpatient	63.6 (1039)	71.2 (3456)
Study site (N = 6490)	Liguria	44.6 (729)	48.2 (2342)	<0.001^a
	Tuscany	1.8 (30)	3.8 (184)
	Lazio	17.9 (292)	11.4 (556)
	Apulia	35.6 (582)	36.5 (1775)
Season (N = 6490)	2018/2019	53.9 (880)	38.1 (1849)	<0.001^a
	2019/2020	41.5 (678)	38.7 (1878)
	2021/2022	1.2 (19)	14.9 (725)
	2022/2023	3.4 (56)	8.3 (405)
Presence of co-morbidities (N = 6490)	No	64.1 (1046)	50.4 (2449)	<0.001^a
	Yes	35.9 (587)	49.6 (2408)
Fever/feverishness (N = 6106)	No	7.7 (122)	18.0 (810)	<0.001^a
	Yes	92.3 (1472)	82.0 (3702)
Swab delay, days (N = 6490)	Mean [SD]	3.1 [1.8]	2.9 [1.8]	<0.001^c
Influenza vaccination (N = 6490)	No	85.9 (1402)	72.4 (3517)	<0.001^a
	Yes	14.1 (231)	27.6 (1340)
Positivity to SARS-CoV-2 (N = 1205)	No	94.7 (71)	70.9 (801)	<0.001^a
	Yes	5.3 (4)	29.1 (329)

^aChi-square test.

^bMann-Whitney test.

^ct test.

^dSeasons 2021/2022 and 2022/2023.

IQR = interquartile range; SD = standard deviation.

Figure 1. Projected weekly decline in influenza vaccine effectiveness in the total cohort (N = 6490) and probability of influenza among vaccinated individuals only (N = 1571), by virus (sub)type; Italy, 2018/2019 to 2022/2023.

Projected (sub)type-specific adjusted vaccine effectiveness in the entire study population of vaccinated and unvaccinated individuals by week since vaccination is depicted using solid lines. Pooled adjusted effectiveness without time since vaccination in the model was 54% (95% CI: 39–65%), 18% (95% CI: -3–34%) and 38% (95% CI: 26–48%) for influenza A(H1N1)pdm09, A(H3N2) and B, respectively. Predicted probabilities of influenza virus (sub)types in vaccinated individuals only are depicted using dashed lines.

Table 2. Association between the time since vaccination and positivity to influenza virus, by virus (sub)type; Italy, 2018/2019 to 2022/2023.

	All subjects		Only vaccinated subjects
Virus	aOR (95% CI)	p-value	aOR (95% CI)	p-value
Any	1.049 (1.020–1.080)	0.001	1.061 (1.028–1.096)	<0.001
A(H1N1)pdm09	1.003 (0.956–1.050)	0.91	1.042 (0.988–1.098)	0.13
A(H3N2)	1.065 (1.029–1.103)	<0.001	1.070 (1.029–1.113)	<0.001
B	1.073 (0.949–1.120)	0.24	1.083 (0.951–1.239)	0.23

aOR = adjusted odds ratio; CI = confidence interval.

Table 3. Association between the time since vaccination and positivity to influenza virus, by age-group and virus (sub)type; Italy, 2018/2019 to 2022/2023.

		All subjects		Only vaccinated subjects
Age-group	Virus	aOR (95% CI)	p-value	aOR (95% CI)	p-value
Children	Any	1.094 (1.013–1.186)	0.024	1.120 (1.023–1.231)	0.016
	A(H1N1)pdm09	0.990 (0.889–1.097)	0.85	1.015 (0.878–1.167)	0.84
	A(H3N2)	1.148 (1.039–1.277)	0.008	1.173 (1.047–1.329)	0.008
	B	1.106 (0.918–1.135)	0.29	1.125 (0.889–1.442)	0.33
Working-age adults	Any	1.004 (0.949–1.061)	0.90	1.016 (0.957–1.079)	0.61
	A(H1N1)pdm09	0.984 (0.894–1.077)	0.73	1.004 (0.909–1.104)	0.94
	A(H3N2)	1.022 (0.953–1.096)	0.53	1.034 (0.957–1.119)	0.40
	B	0.933 (0.719–1.153)	0.56	0.885 (0.587–1.269)	0.50
Older adults	Any	1.061 (1.018–1.106)	0.005	1.065 (1.019–1.115)	0.006
	A(H1N1)pdm09	1.056 (0.979–1.139)	0.16	1.071 (0.987–1.164)	0.10
	A(H3N2)	1.067 (1.015–1.122)	0.011	1.066 (1.011–1.125)	0.020
	B	1.003 (0.786–1.252)	0.98	1.035 (0.795–1.351)	0.79

aOR = adjusted odds ratio; CI = confidence interval.

Table 4. Association between the time since vaccination and positivity to influenza virus: a sensitivity analysis based on the matching procedure to reduce the confounding due to calendar time.

	All subjects			Only vaccinated subjects
Virus	N matched cases/controls	aOR (95% CI)	p-value	N matched cases/controls	aOR (95% CI)	p-value
Any	1580/2928	1.063 (1.026–1.102)	<0.001	229/531	1.076 (1.030–1.125)	0.001
A(H1N1)pdm09	647/1941	1.026 (0.967–1.088)	0.39	73/215	1.086 (1.000–1.182)	0.050
A(H3N2)	697/1733	1.046 (0.994–1.101)	0.085	136/332	1.076 (1.011–1.146)	0.022
B	212/513	0.992 (0.825–1.192)	0.94	NE^a	NE^a	NE^a

^aNot estimable owing to a small number of cases among vaccinees.

aOR = adjusted odds ratio; CI = confidence interval.