Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection

Abstract

Background: In the context of 2009 pandemic influenza (H1N1) virus infection (pandemic H1N1 influenza), identifying correlates of the severity of disease is critical to guiding the implementation of antiviral strategies, prioritization of vaccination efforts and planning of health infrastructure. The objective of this study was to identify factors correlated with severity of disease in confirmed cases of pandemic H1N1 influenza.

Methods: This cumulative case-control study included all laboratory-confirmed cases of pandemic H1N1 influenza among residents of the province of Manitoba, Canada, for whom the final location of treatment was known. Severe cases were defined by admission to a provincial intensive care unit (ICU). Factors associated with severe disease necessitating admission to the ICU were determined by comparing ICU cases with two control groups: patients who were admitted to hospital but not to an ICU and those who remained in the community.

Results: As of Sept. 5, 2009, there had been 795 confirmed cases of pandemic H1N1 influenza in Manitoba for which the final treatment location could be determined. The mean age of individuals with laboratory-confirmed infection was 25.3 (standard deviation 18.8) years. More than half of the patients (417 or 52%) were female, and 215 (37%) of 588 confirmed infections for which ethnicity was known occurred in First Nations residents. The proportion of First Nations residents increased with increasing severity of disease (116 [28%] of 410 community cases, 74 [54%] of 136 admitted to hospital and 25 [60%] of 42 admitted to an ICU; p<0.001), as did the presence of an underlying comorbidity (201 [35%] of 569 community cases, 103 [57%] of 181 admitted to hospital and 34 [76%] of 45 admitted to an ICU; p<0.001). The median interval from onset of symptoms to initiation of antiviral therapy was 2 days (interquartile range, IQR 1-3) for community cases, 4 days (IQR 2-6) for patients admitted to hospital and 6 days (IQR 4-9) for those admitted to an ICU (p<0.001). In a multivariable logistic model, the interval from onset of symptoms to initiation of antiviral therapy (odds ratio [OR] 8.24, 95% confidence interval [CI] 2.82-24.1), First Nations ethnicity (OR 6.52, 95% CI 2.04-20.8) and presence of an underlying comorbidity (OR 3.19, 95% CI 1.07-9.52) were associated with increased odds of admission to the ICU (i.e., severe disease) relative to community cases. In an analysis of ICU cases compared with patients admitted to hospital, First Nations ethnicity (OR 3.23, 95% CI 1.04-10.1) was associated with increased severity of disease.

Interpretation: Severe pandemic H1N1 influenza necessitating admission to the ICU was associated with a longer interval from onset of symptoms to treatment with antiviral therapy and with the presence of an underlying comorbidity. First Nations ethnicity appeared to be an independent determinant of severe infection. Despite these associations, the cause and outcomes of pandemic HINI influenza may involve many complex and interrelated factors, all of which require further research and analysis.

Figure 1

Epidemic curve of laboratory-confirmed cases of 2009 pandemic influenza (H1N1) virus infection in Manitoba according to final location of treatment (n = 889). The epidemic curve represents the dates of onset for confirmed cases, based on the earliest of the following dates: date of onset of symptoms, date of admission to hospital, date on which investigation form was received, date on which specimen was obtained or date on which report was received. For five additional cases, the date of onset according to this definition occurred before Apr. 2, 2009, and these cases are not represented in the figure. ICU = intensive care unit.

Figure 2

Age-specific distribution of confirmed infections by final location of care. ICU = intensive care unit.

Figure 3

Severity of disease in relation to the interval from onset of symptoms to treatment with antiviral agents. Increasing interval from onset of symptoms to antiviral therapy was associated with increased severity of illness. ICU = intensive care unit.

Figure 4

Multivariable correlates of the severity of disease, for comparison between patients cared for in the community and those admitted to an intensive care unit (ICU). CI = confidence interval, OR = odds ratio.

Figure 5

Multivariable correlates of the severity of disease, for comparison between patients admitted to hospital but not to an intensive care unit (ICU) and those admitted to an ICU. CI = confidence interval, OR = odds ratio.