B Lung parenchyma showing chronic fibroproliferative phase of diffuse alveolar damage with marked thickening of the alveolar septa and alveolar space being replaced by fibrogranulation tissues on day 28 of symptom onset in a 37-year-old previously healthy woman (original magnification, imes 200). A Lung parenchyma showing acute exudative phase of diffuse alveolar damage on day 7 after symptom onset in a 42-year-old previously healthy man with interstitial cellular infiltrate and proteinaceous exudates in alveoli and hyaline membrane formation (original magnification, imes 100). Histopathological changes of pulmonary and extrapulmonary tissue (hematoxylin-eosin stained) of the deceased patients suffering from pandemic influenza A H1N1 2009. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations.
The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. We compared their pattern of clinical disease, viral load, and immunological profile.
We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). However, studies comparing virological and immunological profile of different clinical severity are lacking. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases.
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