Autopsy Findings in Eight Patients With Fatal H1N1 Influenza
Abstract and Introduction
A novel H1N1 influenza A virus emerged in April 2009, and rapidly reached pandemic proportions. We report a retrospective observational case study of pathologic findings in 8 patients with fatal novel H1N1 infection at the University of Michigan Health Systems (Ann Arbor) compared with 8 age-, sex-, body mass index–, and treatment-matched control subjects. Diffuse alveolar damage (DAD) in acute and organizing phases affected all patients with influenza and was accompanied by acute bronchopneumonia in 6 patients. Organizing DAD with established fibrosis was present in 1 patient with preexisting granulomatous lung disease. Only 50% of control subjects had DAD. Peripheral pulmonary vascular thrombosis occurred in 5 of 8 patients with influenza and 3 of 8 control subjects. Cytophagocytosis was seen in all influenza-related cases. The autopsy findings in our patients with novel H1N1 influenza resemble other influenza virus infections with the exception of prominent thrombosis and hemophagocytosis. The possibility of hemophagocytic syndrome should be investigated in severely ill patients with H1N1 infection.
Influenza has been recognized as a human illness since the Middle Ages. Influenza outbreaks occur in 2 distinct patterns: endemic (seasonal) and pandemic. Pandemics typically occur decades apart and are associated with influenza A virus strains harboring novel forms of the hemagglutinin molecule. Influenza virus subtypes that have been associated with pandemics include H1N1, H2N2, and H2N3. The most severe influenza pandemic recorded occurred in 1918. It was associated with the H1N1 subtype and claimed approximately 50 million lives worldwide.
In early April 2009, the US Centers for Disease Control and Prevention (CDC) reported swine influenza A (H1N1) in 2 children and raised the possibility of human-to-human transmission. In June 2009, the World Health Organization confirmed an outbreak of human infections with a novel H1N1 influenza A virus and determined that the outbreak met established criteria for a pandemic. The World Health Organization estimates that the novel H1N1 virus spread farther worldwide in 6 weeks than previous pandemic viruses have spread in 6 months. As of October 17, 2009, the CDC estimated between 14 million and 34 million cases of novel H1N1 influenza, with between 2,500 and 6,000 deaths.
The current US case fatality rate for novel H1N1 influenza is estimated to be similar to that for seasonal influenza (0.08%) and lower than the reported case fatality rate for the 1918 pandemic (2.1%). In comparison with seasonal influenza, deaths associated with novel H1N1 infection have disproportionately affected young to middle-aged adults, many of whom lacked known risk factors for serious complications from influenza, a pattern similar to the 1918 influenza pandemic. Animal models and clinical observations suggest that, unlike endemic influenza virus that is detected only in the nasal cavity, novel H1N1 localizes to the lower respiratory tree and the nasal cavity, which may contribute to its virulence.
The histopathologic changes associated with novel H1N1 infection in humans have recently been described in only a limited number of studies. The University of Michigan Health Systems (UMHS; Ann Arbor) received 133 patients with suspected or confirmed novel H1N1 influenza virus infection from May 26 through November 25, 2009, with 16 deaths. Unique clinical findings previously described in novel H1N1 influenza victims at UMHS include obesity, male sex, frequent occurrence of pulmonary thromboemboli, and a high mortality rate among young to middle-aged adults. Autopsies were performed in 8 H1N1 deaths. We reviewed findings from these autopsies to further detail the gross and histopathologic features of fatal novel H1N1 influenza virus infection.