Predictors of influenza severity among hospitalized adults with laboratory confirmed influenza: Analysis of nine influenza seasons from the Valencia region, Spain

Abstract

Purpose: Influenza hospitalizations contribute substantially to healthcare disruption. We explored the impact of ageing, comorbidities and other risk factors to better understand associations with severe clinical outcomes in adults hospitalized with influenza.

Methods: We analysed multi-season data from adults ≥18 years, hospitalized with laboratory-confirmed influenza in Valencia, Spain. Severity was defined as intensive care unit (ICU) admission, assisted ventilation and/or death. Generalized estimating equations were used to estimate associations between risk factors and severity. Rate of hospital discharge was analysed with a cumulative incidence function.

Results: Only 26% of influenza patients had their primary discharge diagnosis coded as influenza. Comorbidities were associated with severity among adults aged 50-79 years, with the highest odds ratio (OR) in patients with ≥3 comorbidities aged 50-64 years (OR = 6.7; 95% CI: 1.0-44.6). Morbid obesity and functional dependencies were also identified risk factors (ORs varying from 3 to 5 depending on age). The presence of increasing numbers of comorbidities was associated with prolonged hospital stay.

Conclusions: Influenza clinical outcomes are aggravated by the presence of comorbidities and ageing. Increased awareness of influenza among hospitalized patients could prompt clinical and public health interventions to reduce associated burden.

Keywords: Spain; comorbidity; death; influenza; severity.

FIGURE 1

Multivariate risk factor analysis results from the four final GEE models. Odds ratios for severe influenza are represented on the x‐axis (Note: Some confidence intervals exceed the x‐axis scale). Study exposures are listed in the y‐axis

FIGURE 2

Time‐to‐discharge analysis with a cumulative incidence function using the method of Fine and Gray, per age strata and adjusted for confounders identified in each final GEE model, evaluating the effect of the comorbidities. Proportion of cumulated patients discharged at every time point represented on y‐axis. Time to discharge in days in x‐axis. *Subhazard ratios for hospital discharge of at least one category were significantly different to the comparison group (no comorbidities) with P < 0.05: HR (1 comorbidity) = 1.35 (95% CI: 1.07–1.71; P = 0.013) for patients 18–49 years old; and HR (3 comorbidities) = 0.70 (0.53–0.92; P = 0.010) for patients 50–64 years. Cumulative incidence function analysis adjusted for sex, smoking status, BMI, vaccination status and virus lineage in the 18–49 age group; BMI and virus lineage in the 50–64 age group; sex, smoking status and functional dependency in the 65–79 age group; and smoking status, BMI, functional dependency and vaccination status in the ≥80 group and the 65–79 age group; and smoking status, BMI, functional dependency and vaccination status in the ≥80 group