Salicylates and Pandemic Influenza Mortality, 1918–1919 Pharmacology, Pathology, and Historic Evidence

Abstract

The high case-fatality rate--especially among young adults--during the 1918-1919 influenza pandemic is incompletely understood. Although late deaths showed bacterial pneumonia, early deaths exhibited extremely "wet," sometimes hemorrhagic lungs. The hypothesis presented herein is that aspirin contributed to the incidence and severity of viral pathology, bacterial infection, and death, because physicians of the day were unaware that the regimens (8.0-31.2 g per day) produce levels associated with hyperventilation and pulmonary edema in 33% and 3% of recipients, respectively. Recently, pulmonary edema was found at autopsy in 46% of 26 salicylate-intoxicated adults. Experimentally, salicylates increase lung fluid and protein levels and impair mucociliary clearance. In 1918, the US Surgeon General, the US Navy, and the Journal of the American Medical Association recommended use of aspirin just before the October death spike. If these recommendations were followed, and if pulmonary edema occurred in 3% of persons, a significant proportion of the deaths may be attributable to aspirin.

Multiple roles of the coagulation protease cascade during virus infection

“…84 It has been hypothesized that aspirin contributed to the incidence and severity of viral pathology in the 1918-1919 influenza pandemic. 85 Moreover, treatment with antipyretics increased mortality in animal models of influenza infection. 86 Consistent with this notion, we observed that impaired hemostasis due to either a genetic deficiency of TF or an absence of PAR4 dramatically increased lung hemorrhage and increased mortality in mice infected with H1N1.…”

Therapy of experimental influenza virus infection with pyrrolidine dithiocarbamate

“…Even the oral uptake of ASA via the drinking water induced significant protection in these mice [42]. In contrast, especially in humans, the administration of ASA was found to increase IAV-caused disease [57]. Therefore, a profound analysis is necessary prior a general recommendation of ASA as a therapeutic approach for influenza [58].…”

Radioiodine-remnant ablation in low-risk differentiated thyroid cancer: pros

“…In addition, the attitudes of caregivers and public opinions contribute to side effects [45] that are not Endocrine otherwise attributable to RAI therapy. For example, Table 1 directly compares side effects and risks of RAI therapy to those of ordinary over-the-counter aspirin [46][47][48][49][50][51][52][53][54], in widespread use since 1899: a medication the public considers exemplifying safety. Objective comparison suggests RAI therapy to be far safer than therapy with aspirin.…”