Predictive clinicopathological features derived from systematic autopsy examination of patients who died with A/HINI influenza infection in the UK 2009-10 pandemic

Background: From April 2009 to January 2010, the pandemic of A/HINI influenza affected the UK. There were > 30,000 infections and 457 deaths (all ages). Reports from other countries had indicated that certain comorbidities were associated with a higher risk of death from HINI infection, and there was a need to identify these factors in the UK population as knowledge of them could lead to improved treatment in the current epidemic and reduced mortality in future epidemics. Objectives: To gather all the available clinical pathology information from autopsies performed on patients dying with known or suspected influenza A/HINI infection, across the UK. To evaluate comorbidities present in these deceased patients; correlate them with the HINI-related pathology and treatment-associated pathology, determine their relative contributions and estimate the significant features associated with death. Methods: To obtain the autopsy reports, standard request letters were sent by e-mail to all histopathologists in the UK on the Royal College of Pathologists list, all the coroners' jurisdictions in England, Wales and Northern Ireland, and to procurators fiscal in Scotland. The letters asked for autopsy reports of the autopsied deceased who included: those with HINI infection, proven before or after death, and those in whom swine flu was unproven but most likely to have been present; those in whom HINI was a minor pathology, as well as those in whom it was the immediate cause of death; those whose cause of death mentioned 'swine flu', 'swine influenza' or 'HINI infection'; and those of any age from infancy to old age. Results: Sixty-eight autopsy reports were received: 19 children (0-15 years) and 49 adults (16+ years). All but two autopsies were medico-legal, and only two (3% of the total) were consented. This sample thus represents 15% of the known 457 deaths from HINI. Median age for children at death was 6 years, for adults it was 41 years. Deaths in children were associated with congenital diseases (47%, 9/19), particularly of the heart and central nervous system. The autopsied children were not obese. Death in adults were associated with pregnancy (three cases in the study, but nationally 12/457 HINI-associated deaths were noted), obesity (50% of adults had a body mass index >= 30 kg/m(2)) and chronic respiratory disease (12%, 6/49 adults). Diabetes did not emerge as a risk factor for death, but learning difficulties did. Nearly all the deaths (94%, 64/68) were a consequence of HINI infection in the respiratory tract. In more than one-third (41%, 28/68) of the deaths, bacterial secondary infection was the significant complication; the pneumococcus was the most common agent identified (25%, 7/28). Limitations: This review is an incomplete medical study of what happened during the epidemic, and the small sample number (68 reports from 457 deaths) limits further speculation. We have no true measure of whether the cases selected for autopsy are representative of the total deaths in terms of pathology and comorbidities. Conclusions: The major comorbidities associated with death from HINI infection were obesity, chronic respiratory disease and pregnancy. Young age at death was confirmed. Congenital disease in children and learning difficulties in adults were also important, but diabetes was not. This methodology of gathering data for research has potential for use in other public health questions, but is dependent on the co-operation of the medico-legal services. These results reinforce the need to enquire further into the pathogenesis of severe and fatal HINI disease, and the circumstances of clinical presentation and rapid evaluation in a time of epidemic influenza.