PCORI Biweekly COVID-19 Scan: Treatment for Acute Respiratory Distress Syndrome, Breathalyzer to Detect Infection (April 14-27, 2022)

ECRI Horizon Scanning has selected the topics below as those with potential for impact relative to COVID-19 in the United States within the next 12 months. All views presented are preliminary and based on readily available information at the time of writing.

Because these topics are rapidly developing, we cannot guarantee the accuracy of this information after the date listed on this publication. In addition, all views expressed in the commentary section are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders. Topics are listed in alphabetical order.

Description

ExoFlo is a biologic drug being investigated by Direct Biologics (Austin, Texas) to treat adults with COVID-19-associated moderate to severe ARDS. ARDS in COVID-19 is a form of severe respiratory failure that is characterized by lung damage, inflammation, and impaired oxygen exchange. In 2020, about 1/3 of hospitalized patients globally developed ARDS, the leading cause of death among patients with COVID-19.

ExoFlo is an extracellular signaling product made up of extracellular vesicles and growth factors isolated from human bone marrow MSCs. MSCs are known to exert immunomodulatory and regenerative effects, mainly through extracellular vesicle production and local hormone (paracrine) signaling. ExoFlo contains multiple regulatory proteins involved in blood vessel formation, cell proliferation, inflammation modulation, tissue regeneration, and cell survival. It might reduce inflammation and facilitate lung tissue repair in patients with ARDS associated with COVID-19.

Direct Biologics recently announced positive data from its phase 2 trial enrolling 120-patients aged 18 to 85 years with hypoxia and requiring noninvasive oxygen support. ExoFlo reportedly demonstrated a 37.6% reduction in 60-day mortality compared with placebo and  reduced time to discharge and ventilator-free days compared with placebo. No reportable adverse events were observed. The treatment received FDA Regenerative Medicine Advanced Therapy (RMAT) designation and has been greenlighted to be investigated further in a phase 3 trial. The treatment is administered intravenously.

We were unable to find information regarding the potential cost of a treatment course of ExoFlo to treat ARDS associated with COVID-19.

Commentary

ARDS has been a leading cause of death in patients with severe COVID-19. Effective treatments are needed, especially since several existing monoclonal antibody treatments are showing limited efficacy against newer variants.

Early feedback from ECRI internal stakeholders suggested that ExoFlo might improve patient survival outcomes because phase 2 data suggest the treatment is associated with a reduction in mortality. ExoFlo is likely to be costly, although if effective, it might decrease hospitalization lengths and result in cost savings.

Because there are other effective pharmacologic therapies for reducing mortality, such as dexamethasone with or without tocilizumab, which might be easier to access and administer to patients than ExoFlo for COVID-related ARDS, uptake might be low to moderate.

More trial data are needed to assess long-term safety and the impact of ExoFlo on the cognitive, psychological, respiratory, and overall functions of patients with COVID-19 who are treated with this therapy.

• Categories: Treatment
• Areas of potential impact: Patient outcomes, health care delivery and process, health care disparities, health care costs

Description

The InspectIR COVID-19 Breathalyzer, developed by InspectIR Systems, LLC (Frisco, Texas), is a portable testing device intended to rapidly detect and identify markers of SARS-CoV-2 infection in exhaled breath.

The device, roughly the size of a piece of carry-on luggage, uses gas chromatography-mass spectrometry to rapidly (within 3 minutes) detect and identify 5 volatile organic compounds associated with SARS-CoV-2 infection in exhaled breath. The FDA reported that in a study of 2409 symptomatic and asymptomatic individuals, the device correctly identified 91.2% of positive samples and 99.3% of negative samples. However, the agency cautions that positive results should be confirmed with a molecular test, and negative results do not conclusively rule out infection and should not be used as the sole basis for treatment or patient management decisions.

On April 14, 2022, the FDA announced it granted the InspectIR COVID-19 Breathalyzer EUA. It is intended for use in adults. The test requires a prescription and must be performed by a qualified, trained operator, and is therefore most likely to be used in medical settings. However, the developer is interested in marketing the device to businesses, sports teams, and the travel industry as a more reliable alternative to temperature screenings.

The first devices are anticipated to become available around July 2022. Although the device’s cost has not yet been announced, the developer indicated that, with a license or subscription, each test might cost about $10 to $12.

Commentary

As COVID-19 cases and hospitalizations decline, many states are lifting COVID-19 restrictions previously put in place to reduce SARS-CoV-2 transmission. Continuing to screen for SARS-CoV-2 is important to keep vulnerable populations safe and to stay vigilant for possible threats posed by future variants.

Early feedback from ECRI internal stakeholders suggested the InspectIR COVID-19 Breathalyzer is a quick, unintrusive means of screening for SARS-CoV-2 infection and might be preferred over nasal swab tests.  Stakeholders noted the test’s negative predictive value was high and thought the test might be less prone to error compared with assay-based tests. Because the test works by detecting volatile organic compounds, its performance might be less affected by potential future variants that might be heavily mutated.

However, stakeholders thought the device’s disruption potential might be diminished by several factors. These included availability of alternative SARS-CoV-2 screening measures (eg, free, at-home rapid antigen tests), the prescription-only nature of the device, the requirement of molecular tests to confirm presumptive positive results, and the device’s estimated throughput limit of 160 tests per day.

• Categories: Screening and Diagnostics
• Areas of potential impact: Patient outcomes, population health, clinician and/or caregiver safety, health care delivery and process, health care disparities

Horizon scanning is a systematic process that serves as an early warning system to inform decision makers about possible future opportunities and threats. Health care horizon scanning identifies technologies, innovations, and trends with potential to cause future shifts or disruptions—positive or negative—in areas such as access to care, care delivery processes, care setting, costs of care, current treatment models or paradigms, health disparities, health care infrastructure, public health, and patient health outcomes.

The PCORI Health Care Horizon Scanning System (HCHSS) conducts horizon scanning to better inform its patient-centered outcomes research investments. Initially, PCORI defined the HCHSS project scope to focus on interventions with high potential for disruption in the United States in 5 priority areas: Alzheimer’s disease and other dementias, cancer, cardiovascular diseases, mental and behavioral health conditions, and rare diseases. In addition, the system captures high-level disruptive trends across all clinical areas, which may lead PCORI to expand the project scope to include other priority areas in the future.

In early 2020, the COVID-19 pandemic created a fast-moving, widespread public health crisis. In May 2020, PCORI expanded its HCHSS to elucidate the landscape of potentially impactful applications for COVID-19. The HCHSS COVID-19 supplement scans for, identifies, monitors, and reports on emerging and available COVID-19-related treatments, diagnostics, preventive measures, management strategies, and systems changes with potential for high impact to patient outcomes—for individuals and populations—in the United States in the next 12 months.

The HCHSS COVID-19 supplement produces 3 main outputs:

• Biweekly COVID-19 Scans (eg, this document) provide ECRI Horizon Scanning with a vehicle to inform PCORI and the public in a timely manner of important topics of interest identified during ongoing scanning and topic identification or through the ECRI stakeholder survey process.
• Status Reports (quarterly) briefly list and describe all COVID-19-related topics identified, monitored, and recently archived.
• High Impact Reports (every 4 months) highlight those topics that ECRI internal stakeholders (eg, physicians, nurses, allied health professionals, public health professionals, first responders, health systems experts, clinical engineers, researchers, business and finance professionals, and information technology professionals) have identified as having potential for high impact relative to COVID-19 in the United States.