PCORI Biweekly COVID-19 Scan: Three Potential Treatments for Long COVID (December 9-22, 2021)
The Briefing provides an at-a-glance view of some important developments in the information universe surrounding COVID-19. The views presented here are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders.
In the United States, to date, an estimated 800 000 people have died from COVID-19, and about 50 million people have contracted the disease. In North America, long COVID or Post-Acute Sequelae of COVID-19 (PASC) is prevalent in about 30% of COVID-19 survivors and is characterized by new or continued debilitating symptoms, such as fatigue, shortness of breath, cough, cognitive impairments, and mood disorders, that persist for months after acute infection.
Although vaccines and boosters might reduce the prevalence of long COVID by limiting the spread of COVID-19, and new treatments for mild to moderate COVID-19 (eg, molnupiravir, Paxlovid) might prevent progression to severe disease, there is still a need to treat the millions of patients living with this new, chronic condition. As such, treatments must address damage across various organ systems, including pulmonary, cardiovascular, neurologic, renal, and musculoskeletal systems (see Topics to Watch for 3 potentially disruptive interventions).
Some reports also suggest that the United States is experiencing a rise in youth mental health issues, more diagnoses of prolonged grief disorder, and a growing number of people with long COVID. The consequences of long COVID might include adults who can no longer work and children who can no longer play.
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.
Allogeneic Mesenchymal Stem Cells to Treat Moderate to Severe Pulmonary Symptoms in Long COVID
At a Glance
- COVI-MSC is a stem-cell-based therapy being investigated to reduce persistent pulmonary symptoms in adults with long COVID.
- At least one-third of patients with long COVID continue to be affected by breathing difficulty or related lung problems months after acute COVID-19 infection.
- COVI-MSC might help relieve lingering respiratory symptoms by reducing inflammation and fibrosis in lung tissue.
- A phase 2 clinical trial is studying the safety and efficacy of COVI-MSC to improve exercise capacity and lung function in adults with moderate to severe long COVID respiratory symptoms. Primary completion is expected in April 2022.
COVI-MSC (Sorrento Therapeutics, Inc, San Diego, California) is a cell-based therapy derived from allogeneic (donor-derived) adipose (fat) mesenchymal stem cells (MSCs). It is under investigation to treat moderate to severe pulmonary symptoms in adults who have long COVID with pulmonary symptoms.
Long COVID is characterized by a variety of symptoms that affect activities of daily living, including shortness of breath, fatigue, and cognitive problems, which last more than 12 weeks after acute COVID-19. Estimates suggest at least one-third of patients experience persistent respiratory symptoms months after acute COVID-19 infection, likely caused by lung damage and systemic inflammation.
Donor-derived MSCs have been found to be effective for treating a range of respiratory indications including acute lung injury and pulmonary fibrosis. In patients with severe COVID-19, allogeneic MSCs were found to decrease inflammatory cytokines, improve survival, and reduce recovery time. The manufacturer also believes that treatment with allogeneic MSCs might reduce the long-term effects associated with pulmonary tissue damage for these patients.
A phase 2 clinical trial is investigating the safety and efficacy of COVI-MSC to improve exercise capacity and lung function in 60 patients with pulmonary symptoms 3 months after recovering from acute COVID-19. The trial’s estimated primary completion is in April 2022. COVI-MSC is administered as an intravenous infusion up to 3 times, on days 0, 2, and 4. We were unable to find information regarding the potential cost of a treatment course of COVI-MSC.
The prevalence of lingering respiratory symptoms in long COVID and uncertainty about how to treat them demonstrates the need for effective therapies.
Early feedback from ECRI internal stakeholders suggested that COVI-MSC might improve patient outcomes, provided that clinical trials confirm the theoretical benefits of suppressing hyperinflammation and reducing lung fibrosis. Stakeholders thought that an effective treatment to preserve lung function in this population could become increasingly important if these patients required intensive pulmonary care in the future that could further strain the health system.
Stakeholders thought COVI-MSC might contribute to health disparities because it is likely to be costly and available only at specialized centers experienced in cell therapy and treating long COVID. Stakeholders also thought many providers would be cautious about offering COVI-MSC until more is known about its long-term safety and the long-term prognosis for patients who have long COVID with persistent respiratory symptoms.
- Categories: Treatment
- Areas of potential impact: Clinician learning curve, patient health outcomes, patient management, disparities, treatment models, understanding
RSLV-132 to Treat Long COVID
At a Glance
- RSLV-132 is a novel RNase-Fc fusion protein designed to remove proinflammatory RNA in circulation to reduce inflammation in patients with long COVID.
- Patients with long COVID often experience symptoms such as fatigue and brain fog. Persistent immune disturbances have been associated with these long-lasting symptoms.
- RSLV-132 digests extracellular RNA to prevent the overactivation of the immune system via Toll-like receptors and the interferon pathway.
- The treatment is being studied in a phase 2 clinical trial in 70 adults with long COVID, with an estimated primary completion date in March 2022.
RSLV-132 (Resolve Therapeutics, LLC, St Petersburg, Florida) is a fusion protein consisting of an antibody Fc region linked to 2 RNase molecules. It is intended to treat fatigue and brain fog, an umbrella term used to describe a cluster of persistent neurological symptoms including impaired thinking, concentration, planning, and memory, associated with long COVID. RSLV-132 works by degrading proinflammatory RNA circulating in patients that activates the immune system via Toll-like receptors and the interferon pathway. Proinflammatory RNA has been linked with some autoimmune diseases and is suspected to play a role in post-COVID-19 immune system overactivation. RSLV-132 is also under investigation to treat lupus and Sjögren syndrome.
Long COVID is characterized by a variety of symptoms, including fatigue, cognitive problems, sleep disturbances, and joint and muscle pain, which last more than 12 weeks after COVID-19 infection. Long COVID has been found to share features with autoimmune conditions, including the accumulation of autoantibodies leading to overactive immune responses and chronic, systemic inflammation, which is thought to contribute to the fatigue and brain fog associated with long COVID.
An ongoing phase 2, randomized, placebo-controlled trial is investigating the effect of weekly infusions of RSLV-132 at a dosage of 10 mg/kg on decreasing fatigue in 70 adults with long COVID reporting fatigue symptoms. The trial’s estimated primary completion is in March 2022. We were unable to find information regarding the potential cost of a treatment course of RSLV-132.
Uncontrolled inflammatory responses after COVID-19 highlight the need for effective treatments. RSLV-132 might improve patient health outcomes by reducing the overactive inflammatory response associated with long COVID.
Early feedback from ECRI internal stakeholders suggested that, if effective, RSLV-132 might treat the multifaceted health issues associated with long COVID, such as brain fog and fatigue, leading to improved patient quality of life. RSLV-132 might allow patients to return to daily activities and normalcy sooner.
However, stakeholders expressed concerns that patients experiencing long COVID fatigue might have difficulty accessing treatment because of the travel required to visit infusion centers weekly, and patient and caregiver quality of life could be disrupted if the treatment course becomes lengthy. Infusion centers might experience care-delivery disruptions by a new stream of patients receiving repeated RSLV-132 infusions. Although blunting the immune response might help with long COVID, it remains unknown whether treatment might cause adverse events such as increased risk or severity of other infections.
- Categories: Treatments
- Areas of potential impact: Patient outcomes, population health, care setting, treatment models, patient management, health care disparities, health care costs
Sodium Pyruvate Nasal Spray (N115) to Treat Long COVID
At a Glance
- Sodium pyruvate nasal spray (N115) is under investigation to treat long COVID symptoms in adults.
- Sodium pyruvate is a natural antioxidant with anti-inflammatory properties. It is also known to increase endothelial nitric oxide, which has been found to be lowered in COVID-19.
- A recently completed, open label, single-arm, phase 2/3 clinical trial found that treatment with sodium pyruvate increased oxygen levels and reduced coughing, sneezing, headaches, body aches, and shortness of breath in 22 adults with long COVID.
- In October 2021, the drug nasal spray’s manufacturer announced that it had submitted data from 17 clinical trials to the U.S. Food and Drug Administration (FDA) to support its use for treating a broad collection of lung and sinus diseases. However, as of mid-December, it appeared that data regarding people with long COVID had not yet been submitted to the FDA.
Sodium pyruvate is a naturally occurring antioxidant being investigated in a patented nasal spray (N115) by EmphyCorp, Inc (Flemington, NJ), to treat long COVID.
Sodium pyruvate is part of the body's inherent antioxidant defense system and has been shown to reduce proinflammatory agents throughout the body. These proinflammatory agents include hydrogen peroxide and cytokines such as interleukin-6, interleukin-8, and tumor necrosis factor. It is also involved in cellular energy production and is known to increase endothelial nitric oxide. Sodium pyruvate apparently treats long COVID by exerting antioxidant and anti-inflammatory effects and by increasing endothelial nitric oxide, which has been found to be lowered in patients with COVID-19.
In a recently completed open label, single-arm, phase 2/3 clinical trial, 22 adults aged up to 40 years with long COVID used the N115 sodium pyruvate nasal spray 3 times daily for 1 week. The treatment was shown to increase blood oxygen saturation and reduce symptoms of coughing, sneezing, headaches, body aches, and shortness of breath. In October 2021, the manufacturer announced that it had submitted data from 17 clinical trials to the FDA to support its use for treating a broad collection of lung and sinus diseases. However, as of mid-December, it appeared that data regarding people with long COVID had not yet been submitted to the FDA. We were unable to find information regarding the potential cost of a treatment course of sodium pyruvate nasal spray.
Long COVID symptoms persist for months after acute COVID-19 infection and impact patients' ability to work and perform other activities of daily living. Treatment with sodium pyruvate nasal spray might improve health outcomes and quality of life for individuals with long COVID.
Early feedback from internal ECRI stakeholders suggested that, if effective, sodium pyruvate nasal spray might be a relatively safe, convenient, and low-cost treatment. As an at-home treatment, the nasal spray might improve access to care and patient adherence to treatment recommendations, as well as reduce disparities, compared with treatments that can be costly or require multiple health care visits. Improved physical health and return to normal activities might also improve patient mental health.
Additional data are needed to determine whether sodium pyruvate nasal spray can resolve long COVID. Stakeholders had concerns regarding the length of the treatment and whether the treatment alone is sufficient to fully resolve long COVID symptoms.
- Categories: Treatments
- Areas of potential impact: Patient outcomes, population health, patient management, care setting, health disparities, cost
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.
Commentary in this COVID-19 Scan reflects preliminary views of ECRI Horizon Scanning and internal ECRI stakeholders.
The information contained in this document has not been vetted by other stakeholders.
We welcome your comments on this Scan. Send them by email to [email protected].
Posted: December 28, 2021
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