Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola

Abstract

There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases. Most scientists work on new drugs that target viruses, and few accept the idea of treating the host response with generic drugs. A great deal of research will be needed to show conclusively that these drugs work, and this will require the support of public agencies and foundations. Investigators in developing countries should take an active role in this research. If the next Public Health Emergency of International Concern is caused by an emerging virus, a "top down" approach to developing specific new drug treatments is unlikely to be effective. However, a "bottom up" approach to treatment that targets the host response to these viruses by using widely available and inexpensive generic drugs could reduce mortality in any country with a basic health care system. In doing so, it would make an immeasurable contribution to global equity and global security.

The Damage–Response Framework as a Tool for the Physician-Scientist to Understand the Pathogenesis of Infectious Diseases

“…Recognition of the importance of inflammation and immunologically mediated damage in the pathogenesis of infectious diseases has led to calls for the use of agents that reduce the inflammatory response in clinical management [18][19][20]. Although this is a rational suggestion, adjunctive use of anti-inflammatory agents to reduce or proinflammatory agents to augment the immune response has not been reliable or predictably successful.…”

The top 2,000 cited articles in critical care medicine: a bibliometric analysis

“…These critically ill patients with multiple comorbidities are at increased risk of in-hospital morbidity and mortality. Furthermore, CCM plays an essential role in the management of bird flu influenza pandemics, injuries caused by motor vehicle collisions, septic shock and natural disasters (4,5). Therefore, CCM is receiving greater attentions from researchers and healthcare professionals.…”

Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses

“…Importantly, the antiviral effect of statins and fibrates is not restricted to respiratory RNA viruses. These agents are also effective in controlling hepatitis C virus (Ikeda et al, 2006), Andes virus (Petersen et al, 2014), HIV (del Real et al, 2004), and Ebola virus infections (Fedson, 2016). Overall, these studies suggest that cholesterol could be an attractive target for broad-spectrum antivirals against clinically important enveloped viruses.…”