Clinical characteristics and outcomes in hospitalized adult influenza patients: an observational study from Norway 2014–2018

Figures & data

Table 1. Patient characteristics and distribution of influenza (sub)types over the 4 consecutive influenza seasons.

	Total	Season 1 2014–2015	Season 2 2015–2016	Season 3 2016–2017	Season 4 2017–2018
Patients, n (%)	156 (100)	41 (26.3)	28 (17.9)	35 (22.4)	52 (33.3)
Females, n (%)	82 (52.6)	23 (56.1)	15 (53.6)	15 (42.9)	29 (55.8)
Age, median (range)	70 (18–102)	74 (32–95)	55 (25–95)	71 (26–102)	65 (18–90)
Age ≥ 65 years, n (%)	93 (59.6)	30 (73.2)	11 (39.3)	25 (71.4)	27 (51.9)
Predisposing conditions, n (%)
Cardiovascular disease	75 (48.1)	25 (61.0)	8 (28.6)	20 (57.1)	22 (42.3)
Pulmonary disease	54 (34.0)	16 (39.0)	6 (21.4)	12 (34.3)	19 (36.5)
Diabetes	26 (16.7)	6 (14.6)	4 (14.3)	7 (20.0)	9 (17.3)
Immunosuppression	21 (13.5)	8 (19.5)	4 (14.3)	3 (8.6)	6 (11.5)
Neurological disease	18 (11.5)	6 (14.6)	0	6 (17.1)	6 (11.5)
Malignancies	10 (6.4)	5 (12.2)	4 (14.3)	1 (2.9)	0
Renal disease (GFR < 59 ml/min/1.73 m²)	12 (7.7)	2 (4.9)	2 (7.1)	4 (11.4)	4 (7.7)
Obesity (BMI ≥ 30 kg/m^2)	8 (5.1)	4 (9.8)	2 (7.1)	1 (2.9)	1 (1.9)
Liver disease	3 (1.9)	0	2 (7.1)	1 (2.9)	0
Pregnancy	4 (3.0)	0	2 (7.1)	2 (5.7)	1 (1.9)
≥1 predisposing condition	122 (78.2)	35 (85.4)	19 (67.9)	30 (85.7)	38 (73.1)
≥2 predisposing conditions	68 (43.6)	24 (58.5)	7 (25.0)	18 (51.4)	19 (36.5)
No predisposing conditions and age <65 years, n (%)	21 (13.5)	3 (7.3)	7 (25.0)	2 (5.7)	9 (17.3)
Seasonal influenza vaccination^a, n (%)	51 (32.7)	16 (39.0)	9 (32.1)	10 (28.6)	16 (30.8)
Influenza strains and subtypes, n (%)
Influenza A(H3N2)	82 (52.6)	26 (63.4)	4 (14.3)	33 (94.2)	19 (36.5)
Influenza A(H1N1)	20 (12.8)	0	18 (64.4)	0	2 (3.8)
Influenza A na^b	3 (1.9)	1 (2.4)	1 (3.6)	0	1 (1.9)
Influenza B	51 (32.6)	14 (34.1)	5 (17.9)	2 (5.7)	30 (57.6)

^aReceived seasonal influenza vaccine in the season they were hospitalized. For seven patients, the vaccination status was unknown, and they were defined as ‘not vaccinated’.

^bSubtype not available.

Table 2. Symptoms, pneumonia and clinical risk scores on admission, total and by age group.

	Total	<65 years of age	≥65 years of age	p Value (chi^2)
Patients, n (%)	156 (100.0)	63 (40.4)	93 (59.6)	–
Self-reported symptoms
Cough, n (%)	145 (93.0)	61 (96.8)	84 (90.3)	.12
Fever^a, n (%)	120 (76.9)	57 (90.5)	63 (67.7)	.001
Dyspnoea, n (%)	111 (71.2)	45 (71.4)	66 (71.0)	.95
Muscle pain, n (%)	97 (62.2)	45 (71.4)	52 (55.9)	.050
Sore throat, n (%)	90 (57.7)	45 (71.4)	45 (48.4)	.004
Headache, n (%)	82 (52.6)	46 (73.0)	36 (38.7)	<.001
Rhinorrhea, n (%)	62 (39.7)	28 (44.4)	34 (36.6)	.32
Chest pain, n (%)	55 (35.3)	25 (39.7)	30 (32.3)	.34
Gastrointestinal, n (%)	37 (23.7)	15 (23.8)	22 (23.7)	.98
Number of symptoms, median (range)	5 (1–9)	6 (2–9)	5 (1–9)	.0001^b
≥5 symptoms, n (%)	98 (62.8)	51 (81.0)	47 (50.5)	<.001
Pneumonia on admission	73 (46.8)	24 (38.1)	49 (52.7)	.073
Clinical risk score on admission
CRB^high, c, n (%)	54 (34.6)	19 (30.2)	35 (37.6)	.34
CRB65^high, n (%)	35 (22.4)	0	35 (37.6)	<.001
SIRS^high, n (%)	39 (25.0)	15 (23.8)	24 (25.8)	.78
qSOFA^high, n (%)	22 (14.1)	7 (11.1)	15 (16.1)	.38

^aMeasured or subjective.

^bWilcoxon rank-sum test.

^cCRB is a modified CRB65 score, where age of the patients no longer is part of the score.

p values <.05 are indicated in bold and italic.

Table 3. Severe outcomes and associations with patient characteristics, laboratory data, clinical risk scores and antimicrobial treatment.

	Treatment in intensive care unit (ICU)				Oxygen supplementation at any time				≥5 days in hospital
Patients, n (%)	9 (5.8)				67 (43.0)				74 (47.4)
	Crude OR^a (95% CI)	p Value	adjOR^b (95% CI)	p Value	Crude OR (95% CI)	p Value	adjOR (95% CI) ^c	p Value	Crude OR (95% CI)	p Value	adjOR (95% CI)	p Value
Patients’ characteristic
Age (cont.)	1.02 (0.98, 1.07)	.26	1.02 (0.97, 1.06)	.44	1.03 (1.01, 1.05)	.001	1.03 (1.01, 1.05)	.004	1.05 (1.3, 1.07)	<.001	1.04 (1.02, 1.06)	<.001
Females, 82 (52.6)	0.71 (0.18, 2.74)	.62	0.76 (0.19, 2.99)	.70	1.66 (0.87, 3.15)	.12	1.99 (1.00, 3.93)	.049	0.74 (0.39, 1.39)	.35	0.85 (0.43, 1.68)	.63
≥2 predisposing conditions, 68 (43.6)	2.74 (0.66, 11.39)	.17	2.26 (0.52, 9.87)	.28	2.07 (1.08, 3.95)	.03	1.63 (0.81, 3.27)	.17	2.53 (1.32, 4.85)	.005	1.71 (0.84, 3.44)	.14
Pneumonia on admission, 73 (46.8)	1.45 (0.37, 5.63)	.59	1.22 (0.31, 4.85)	.78	3.52 (1.81, 6.85)	0.001	3.52 (1.73, 7.17)	.001	2.40 (1.26, 4.58)	.008	2.11 (1.05, 4.23)	.036
Influenza vaccine in season of admission, 1 (32.7)	1.03 (0.25, 4.30)	.97	0.79 (0.18, 3.42)	.75	1.01 (0.51, 1.99)	.97	0.70 (0.34, 1.47)	.35	1.24 (0.63, 2.41)	.54	0.82 (0.39, 1.72)	.60
Laboratory data
Pos. bacterial airway samples on admission^c, 55 (36.7)	1.41 (0.36, 5.49)	.62	1.61 (0.39, 6.57)	.51	1.70 (0.87, 3.33)	.12	1.77 (0.85, 3.67)	.12	1.65 (0.85, 3.22)	.14	2.06 (0.97, 4.35)	.06
CRP (mg/L) on admission [cont.]	1.00 (0.99, 1.01)	.62	1.00 (0.99, 1.01)	.52	1.00 (1.00, 1.01)	.036	1.01 (1.00, 1.01)	.015	1.00 (1.00, 1.01)	.21	1.00 (1.00, 1.01)	.09
Clinical risk scores
CRB^high, d, 54 (34.6)	17.56 (2.13, 144.58)	0.008	15.38 (1.84, 128.96)	0.012	4.03 (2.01, 8.10)	<.001	4.08 (1.93, 8.63)	<.001	2.08 (1.06, 4.06)	.033	1.79 (0.86, 3.73)	.12
CRB65^high,e, 35 (22.4)	4.88 (1.23, 19.27)	0.024	3.91 (0.89, 17.08)	0.07	4.70 (2.06, 10.71)	<.001	4.70 (1.93, 11.42)	.001	3.67 (1.62, 8.33)	.002	2.83 (1.20, 6.69)	.018
SIRS ^high, 39 (25.0)	0.85 (0.17, 4.27)	0.84	0.80 (0.15, 4.14)	0.79	4.33 (1.99, 9.45)	<.001	5.14 (2.18, 12.12)	<.001	1.41 (0.68, 2.92)	.36	1.58 (0.70, 3.56)	.27
qSOFA^high, 22 (14.1)	3.37 (0.78, 14.61)	0.11	2.99 (0.66, 13.51)	0.16	2.67 (1.05, 6.81)	.039	2.37 (0.87, 6.40)	.09	2.16 (0.85, 5.49)	.11	1.95 (0.70, 5.46)	.20
Antimicrobial treatment
Antiviral treatment, 58 (37.2)	3.65 (0.88, 15.22)	0.08	4.23 (0.99, 8.09)	0.052	1.58 (0.82, 3.04)	.17	1.84 (0.91, 3.72)	.092	0.76 (0.39, 1.46)	.41	0.84 (0.41, 1.70)	.62
Antibiotic treatment, 121 (77.6)	1.01 (0.20, 5.11)	0.99	0.95 (0.18, 4.89)	0.95	3.93 (1.60, 9.69)	.003	4.14 (1.61, 10.62)	.003	2.37 (1.07, 5.26)	.034	2.58 (1.10, 6.06)	.029

^aLogistic regression analyses. OR: odds ratio

^badjOR: odds ratio (OR) adjusted for age, sex and having ≥2 predisposing conditions.

^cSix patients did not have an airway sample for bacterial culture, n = 150.

^dCRB is a modified CRB65 score, where age of the patients no longer is part of the score.

^eNot adjusted for age, as age is part of the score.

p values <.05 are indicated in bold and italic.

Figure 1. Symptoms, clinical risk scores and outcomes of disease and according to influenza (sub)types. (a) Percentage of patients self-reporting specific symptoms prior to admission. (b) Percentage of patients with high clinical risk scores on admission defined by CRB, CRB65, SIRS and qSOFA criteria. CRB is a modified CRB65 score, where age of the patients no longer is part of the score. (c) Percentage of patients with various severe outcomes. Oxygen: oxygen supplementation and ICU: intensive care unit. *indicates p<.05 and **indicates p < 0.01 (chi² analyses).

Figure 2. Use of antimicrobial treatment according to influenza season and influenza (sub)types. (a) Percentage of patients receiving antiviral and antibiotic treatment over the four consecutive influenza seasons. For each treatment type, season 1 is compared with the other seasons. (b) Percentage of patients receiving antiviral and antibiotic treatment according to their influenza (sub)types. *indicates p<.05 and **indicates p<.01 (chi² analyses).

Table 4. Antiviral and antibiotic treatment and associations with patient characteristics, laboratory data and risk scores.

		Antiviral treatment 58 (37.2)			Antibiotic treatment 121 (77.6)
Patients, n (%)
	Crude OR^a (95% CI)	p Value	adjOR^b (95% CI)	p Value	Crude OR (95% CI)	p Value	adjOR (95% CI)	p Value
Patients’ characteristics
Age (cont.)	0.99 (0.98, 1.01)	.34	1.00 (0.98, 1.02)	.71	1.00 (0.98, 1.02)	.90	1.00 (0.98, 1.03)	.70
Females	1.32 (0.69, 2.54)	.41	1.51 (0.73, 3.11)	.26	1.43 (0.67, 3.03)	.36	1.44 (0.66, 3.13)	.36
≥2 predisposing conditions	0.77 (0.40, 1.50)	.45	0.78 (0.36, 1.69)	.54	1.21 (0.56, 2.60)	.63	1.35 (0.59, 3.11)	.48
Days from symptom onset to hospitalization	0.81 (0.70, 0.93)	.004	0.77 (0.66, 0.91)	.001	0.93 (0.85, 1.02)	.12	0.93 (0.84, 1.02)	.12
Influenza seasons
Season 1 (2014-2015)	1 (Ref)	–	1 (Ref)	–	1 (Ref)	–	1 (Ref)	–
Season 2 (2015-2016)	1.98 (0.68, 5.76)	.21	1.93 (0.61, 6.10)	.26	2.2 (0.62, 7.79)	.22	2.68 (0.71, 10.14)	.15
Season 3 (2016-2017)	3.76 (1.39, 10.16)	.009	5.18 (1.76, 15.23)	.003	1.24 (0.43, 3.53)	.69	1.54 (0.51, 4.61)	.44
Season 4 (2017-2018)	2.41 (0.96, 6.07)	.06	3.01 (1.11, 8.20)	.031	1.22 (0.47, 3.15)	.68	1.44 (0.54, 3.87)	.47
Pneumonia on admission	0.98 (0.51, 1.89)	.96	1.30 (0.62, 2.69)	.49	4.80 (1.95, 11.83)	.001	7.24 (2.57, 20.4)	<.001
Influenza vaccine in season of admission	0.69 (0.34, 1.39)	.30	0.89 (0.40, 1.95)	.77	1.08 (0.48, 2.42)	.86	1.14 (0.48, 2.71)	.77
Laboratory data
CRP (mg/L) on admission [cont.]	1.00 (0.99, 1.00)	.41	1.00 (0.99, 1.00)	.85	1.04 (1.02, 1.05)	<.001	1.04 (1.02, 1.06)	<.001
Bacterial findings on admission^c	0.76 (0.38, 1.53)	.45	0.97 (0.43, 2.15)	.93	3.08 (1.18, 8.04)	.02	4.28 (1.54, 11.87)	.005
Clinical risk scores
CRB^high, d	1.26 (0.64, 2.48)	.50	1.20 (0.56, 2.60)	.64	2.07 (0.87, 4.94)	.10	2.03 (0.81, 5.07)	.13
CRB65^high, e	0.85 (0.39, 1.87)	.69	0.69 (0.27, 1.76)	.43	2.67 (0.87, 8.17)	.09	2.81 (0.83, 9.49)	.10
SIRS^high	2.19 (1.05, 4.58)	.04	2.19 (0.97, 4.94)	.06	3.15 (1.04, 9.60)	.043	3.16 (1.01, 9.83)	.047
qSOFA^high	0.33 (0.11, 1.03)	.06	0.24 (0.07, 0.84)	.025	7.14 (0.93, 55.10)	.06	6.04 (0.77, 47.66)	.09

^aLogistic regression analyses. OR: odds ratio

^badjOR: odds ratio (OR) adjusted for age, sex, having ≥2 predisposing conditions, influenza season and days between symptom onset and admission.

^cSix patients did not have an airway sample for bacterial culture, n = 150.

^dCRB is a modified CRB65 score, where age of the patients no longer is part of the score.

^eNot adjusted for age, as age is part of the score.

p values <.05 are indicated in bold and italic.