Janelle Ayres shares insights in “Surviving COVID-19: A Disease Tolerance Perspective”
May 11, 2020
NOMIS researcher Janelle Ayres, a molecular and systems physiologist at the NOMIS Center for Immunobiology and Microbial Pathogenesis at the Salk Institute for Biological Studies, has published an editorial on COVID-19 treatment in the journal Science Advances.
Surviving COVID-19: A Disease Tolerance Perspective
In December 2019, an epidemic of pneumonia of unknown cause emerged in Wuhan, China. In early January 2020, a virus was sequenced and identified as a novel coronavirus named SARS-CoV-2, the causative agent of COVID-19. By March 2020, the World Health Organization (WHO) declared the outbreak a pandemic with current numbers reaching over 1 million individuals infected and approximately 75,000 deaths globally. There has always been a disconnect between our methods for treating infectious diseases and our understanding of the mechanisms that promote the survival of infections (1). This global pandemic has underscored the necessity to understand how it is that we survive infections and why this may be different from the ways we often think about the treatment of infectious diseases.
A successful response to any infectious disease outbreak requires a multipronged approach. With COVID-19, governments are enforcing unprecedented quarantines and social distancing measures to facilitate the containment and reduce transmission of the virus, efforts that are proving to be effective. Scientists from private and public sectors are racing to identify a successful vaccine, which will be essential for the prevention of future infections and mortalities, thereby reducing pressures on the healthcare system, economy, and society. Where these efforts fall short are with the current approaches for developing treatments for those that are sick with and dying from a COVID-19 infection. The current potential COVID-19 treatments being tested include antivirals already in use for HIV, antimalarial drugs and other compounds that may prevent viral replication, and convalescent serum. The WHO has a similar focus on identification of therapies that destroy the virus with their launch of the SOLIDARITY trial that is streamlining the testing of multiple antiviral strategies that may be effective against COVID-19 (2). The unifying goal for these therapeutic efforts is the identification of drugs that target the virus to inhibit viral replication.
Antivirals will likely be effective for the fraction of infected patients that develop “mild” cases of COVID-19 by shortening their length of infection and for reducing transmission to naïve individuals, but for the patients who develop severe and critical disease and who are destined for hospitalization and intensive care, the antiviral-based strategy does not jive with what is needed at the frontlines, where the medics and patients are fighting for life. These patients progress to severe and critical stages associated with pneumonia, acute respiratory distress syndrome (ARDS) and respiratory failure, septic shock, and multiorgan dysfunction (3), conditions that are caused by the host response to the virus. With these patients, the issue at hand is to sustain physiological function and buy them time so that they can get off the path to death and begin one toward recovery. To do this, doctors rely on supportive care such as mechanical ventilators, fluids, oxygen, blood pressure, and anticlotting medications, not antivirals. The importance of identifying effective methods to target the host response to the infection rather than developing specific antivirals for the critically ill patients is underscored by clinical data involving patients with influenza. Approximately 25% of critically ill patients that receive optimal antiviral therapy still die (4). This implicates that the host response to the virus is a major factor in determining the outcome of an influenza and, likely, COVID-19 infections. So, while hospitals and governments race to find sufficient amounts of supportive care equipment as their health care systems are threatened with exceeding capacity, scientists are focused on developing antivirals and not on drugs that promote physiological function during the infection. In addition to developing antivirals, we need therapeutics that perform the functions of supportive care so that doctors are better equipped with an arsenal of therapies that can target any aspect of the patient’s physiology to sustain its function. Such therapies will not only operate to promote survival but also come with less risk of the pathogen developing drug resistance that will eventually happen with the antivirals because these strategies target the health of the host and not the virus (5).
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Professor in the NOMIS Center for Immunobiology and Microbial Pathogenesis, director of the Molecular and Systems Physiology Laboratory, member of the Gene Expression Laboratory, and Helen McLoraine Developmental Chair
Salk Institute for Biological Studies
NOMIS Center for Immunobiology and Microbial Pathogenesis
Harnessing Physiological Health to Treat Disease
NOMIS RESEARCH PROJECT