Changes in Severity of Influenza A(H1N1)pdm09 Infection from Pandemic to First Postpandemic Season, Germany

Nicola Lehners¹, Steffen Geis¹, Christoph Eisenbach, Kai Neben, and Paul Schnitzler

Author affiliations: Author affiliation: University of Heidelberg, Heidelberg, Germany

Abstract

We studied risk factors for a severe clinical outcome in hospitalized patients with laboratory-confirmed influenza A(H1N1)pdm09 infection at the University Hospital Heidelberg in the pandemic and first postpandemic seasons. We identified 102 patients in 2009–10 and 76 in 2010–11. The proportion of severely diseased patients dramatically increased from 14% in 2009–10 to 46% in 2010–11 as did the mortality rate (5%–12%). Patients in the first postpandemic season were significantly older (38 vs. 18 years) and more frequently had underlying medical conditions (75% vs. 51%). Overall, 50 patients (28%) had a severe clinical outcome, resulting in 14 deaths. Multivariate analysis showed that older male patients with chronic lung disease were at increased risk for a severe clinical outcome. In summary, the proportion of patients with severe disease and fatal cases increased in the postpandemic season. Therefore, patients with suspected infections should be promptly identified and receive early treatment.

Influenza pandemics have been associated with increased illness and death. Each pandemic is different, and areas of uncertainty always exist when an influenza virus emerges and becomes pandemic. In April 2009, the novel influenza A(H1N1)pdm09 virus emerged in Mexico and then spread rapidly throughout the world (1). Influenza is generally a self-limiting infection with systemic and respiratory symptoms that usually resolve after 3–6 days. Most persons infected with the 2009 influenza A(H1N1)pdm09 virus experienced uncomplicated illness with full recovery within 1 week, even without medical treatment; severe progressive disease developed in only a small subset of patients (2). Primary viral pneumonia was the most common finding in severe cases, but secondary bacterial infections played a role in ≈30% of fatal cases (3). Hospitalized patients were often affected by other medical conditions, such as diabetes and cardiovascular, neurologic and pulmonary diseases (4). Advances in therapy for malignancies, autoimmune disorders, and end-stage organ diseases have led to improved survival, but also to an increase in the number of immunosuppressed patients. These patients are particularly at risk for opportunistic and community-acquired infections, such as respiratory virus infections, resulting in considerable illness and death (5).
Although patients hospitalized with pandemic influenza A(H1N1)pdm09 infection had substantial severe illness, the overall number of deaths was lower than reported in the earliest studies. The overall number of deaths caused by influenza A(H1N1)pdm09 infection was similar to that caused by seasonal influenza and lower than that of previous pandemics (6). The most common cause of death was respiratory failure (7). Other reported causes of death included pneumonia, high fever leading to neurologic sequelae, dehydration from excessive vomiting and diarrhea, and electrolyte imbalance. Severe cases were most frequent in middle-aged patients, who often had coexisting conditions (7). Although to date there seems to be no major difference between the virulence of influenza A(H1N1)pdm09 strains and seasonal influenza (8) strains, a more aggressive course in specific populations, such as in young patients and pregnant women, has been reported (9,10). Further risk factors include obesity, chronic lung disease, chronic heart disease, chronic renal disease, diabetes mellitus, and severe immunosuppression (4,11,12). Contradictory findings have been reported in regard to varying disease severity during the pandemic season. Although some researchers did not observe any differences in disease severity between the first and second pandemic outbreaks in 2009 (13,14), another study showed a 4-fold increase in hospitalization and a 5-fold increase in number of deaths in the second wave (15). However, disease severity of postpandemic seasons has been rarely analyzed.
We performed a retrospective analysis of all patients with laboratory-confirmed influenza A(H1N1)pdm09 virus infection who were hospitalized at the University Hospital Heidelberg, Germany, in the pandemic season 2009–10 and the first postpandemic season 2010–11 to compare the rates of severely diseased patients in both seasons and to identify possible risk factors associated with severe clinical outcome.