Guest Post: COVID-19 and the Challenging Acute Respiratory Distress Syndrome (ARDS)

Three weeks ago, my son’s 68-year-old father-in-law (KS) was admitted to a New Jersey hospital ER with 2 days of fever, cough and increasing respiratory distress. He was COVID-19 positive with low blood oxygen levels that failed to improve despite high oxygen supplementation. Over the next 12 hours, he developed severe respiratory fatigue requiring intubation and mechanical ventilation, Acute Respiratory Distress Syndrome [ARDS]. My daughter-in-law, a resident at Georgetown Medical Center, asked for my involvement in his respiratory management because I am an academic pulmonary/critical care physician-scientist and CEO/Founder of an early stage ARDS-focused biotech company.

KS’s admission to the ICU with COVID ARDS brought home the sad and sobering reality that ARDS management is largely supportive care and the use of a mechanical ventilator. There is not a single FDA-approved drug for ARDS and until the COVID-19 pandemic, only a handful of investigational drugs in clinical trials. We need to do better.

This Patient Cannot Wait

ARDS, initially identified in Vietnam soldiers experiencing battlefield trauma, and even before COVID, was annually affecting over half a million people in the US and over 2 million people globally with a staggering mortality rate approaching 40%. ARDS occurs when the body releases a tsunami of inflammatory mediators in response to sepsis (infection in the blood), severe trauma, and severe bacterial or viral pneumonias. This ‘cytokine storm’ directly causes leakiness of blood vessels and lowers oxygen levels in multiple vital organs (kidneys, heart, brain), and the fluid accumulation in the lung and makes breathing quite difficult. Often, a ventilator is needed as the lungs begin to fail and is lifesaving. Unfortunately, the ventilator is a two-edged sword and can also directly increase inflammation and contribute to ARDS deaths via multi-organ failure. We and others are seeing these events occuring in COVID-19-infected patients who progress to full blown ARDS.

Given KS’s age, co-morbidities and elevated mortality rates, we opted to optimize KS’s ARDS course and utilized four unapproved drugs that were chosen for the potential to diminish the inflammation produced by the COVID-19 infection and the ventilator.

·         Hydrochloroquine is an anti-malarial also used as an anti-inflammatory to treat autoimmune diseases and recently touted as having anti-SARS-CoV2 viral effects. There is no clinical trial data however, in patients with established ARDS. More recently, high dose hydroxychlorine was found to be associated with cardiac arrhythmias. We, fortunately, utilized low dose hydroxychlorine.

·         Azithromycin is an antibiotic that exhibits known anti-inflammatory properties.

·         Simvastatin has a remarkable safety profile was shown (by my Johns Hopkins research laboratory) to have anti-inflammatory properties and potentially capable of reducing both lung vascular leak and injury and may be beneficial in select ARDS subjects.

·         Tocilizumab is an antibody-based therapy used in cancer treatments which neutralizes a specific inflammatory cytokine called interleukin-6, which may calm the inflammation associated with ARDS. Information regarding Tocilizumab efficacy is mixed to date.

Hydrochloroquine, Azithromycin and Simvastatin were administered upon admission and Tocilizumab was started after intubation.

Fortunately, KS’s respiratory status stabilized and improved over the next 3 days. This allowed us to take him off the ventilator, and several days later, he was discharged from the hospital to a rehab facility where he continues to improve.

Hope and the Need for Action

The exact contribution of each drug to KS’s successful COVID-19 ARDS outcome is impossible to define. While science and clinical medicine will assuredly defeat the SARS-CoV-2 virus and COVID-19-like infections and improve outcomes for all ARDS victims, this will require the conduct of rigorous clinical trials of potential ARDS therapies in order to avoid the empiric use of anecdotal or unvalidated therapies.

My company, Aqualung Therapeutics, has developed an anti-inflammatory platform that consists of a humanized monoclonal antibody, that neutralizes an early key ARDS driver of unchecked inflammation, and as part of the therapeutic platform includes a genetic and biomarker tests that may allow selection of ARDS patients most likely to respond to our antibody. Such Precision Medicine approaches will be critical to future clinical trial design evaluating ARDS therapeutics.

It appears entirely likely that to dramatically moving the needle on ARDS mortality, will require a combination of potent anti-inflammatory therapeutics like management of many cancers. It is a frustrating reality that we have waited far too long for FDA-approved ARDS therapies. Given the likelihood of future pandemics and the annual numbers of ARDS patients with this vexing clinical challenge, we simply cannot afford to wait any longer.

Joe G. N. “Skip” Garcia, MD, an academic pulmonary physician-scientist, former Chief of Pulmonary and Critical Medicine at Johns Hopkins University, and an elected member of the National Academy of Medicine. He is an endowed professor of medicine at the University of Arizona College of Medicine – Tucson and leads the Garcia Lab at the University of Arizona. Dr. Garcia also is a leading authority on the genetic basis of lung disease and the prevention and treatment of inflammatory lung injury including ARDS. He is also the CEO of Aqualung Therapeutics, a Tucson-based biotech company developing a novel, anti-inflammatory monoclonal antibody. 

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