PCORI Biweekly COVID-19 Scan: Treating COVID-19-Associated Lung Failure, New Vaccine for Prevention (June 9-22, 2022)
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.
Apparent consequences of the COVID-19 pandemic continue to emerge. Preliminary findings suggest that children born to mothers who tested positive for SARS-CoV-2 during their pregnancies might be more likely to be diagnosed with motor, speech, and language disorders in their first year of life. Whether the link is causal remains to be seen, but these children will need increased care, perhaps throughout their lives.
The prevalence of post-COVID conditions, or post-acute sequelae of COVID-19 (PASC), might also be causing an increased demand for health care. Good news out of the United Kingdom showed that the odds of developing long COVID might be 20% to 50% lower for those infected with the Omicron variant than for those infected by the Delta variant. However, the number of Omicron infections in the United States is so large that if even a small percentage of those with Omicron infection develop long COVID, health care demand might increase (see Topics to Watch for a new vaccine that targets some Omicron variants).
In addition, reinfection rates are likely to rise as new lineages of the Omicron variant that can evade previously acquired immunity begin to dominate in the United States. A recent preprint using US Department of Veterans Affairs electronic health records warns that reinfection might increase the risk of mortality, hospitalization, and multiple disorders, ranging from lung diseases (see Topics to Watch for a potential treatment for associated lung failure) to poor mental health in both unvaccinated and vaccinated people compared with non-infected people.
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.
JadiCell to Treat COVID-19–Associated Lung Failure
At a Glance
- JadiCell is a mesenchymal stem cell (MSC) therapy under investigation to treat COVID-19–associated lung failure.
- The therapy is said to suppress lung inflammation by altering inflammatory signaling pathways thought to modulate scar tissue repair as well as stimulating endogenous lung stem cells and the formation of new blood vessels, which might reduce lung damage, preserve lung function, and promote healing, potentially improving clinical outcomes.
- Results from a phase 1/2, randomized, placebo-controlled trial of hospitalized participants with COVID-19–associated lung injury showed that JadiCell significantly improved patient survival and time to recovery compared with standard-of-care treatment.
- In May 2022, the developer announced a planned phase 3 clinical trial of JadiCell in 128 patients with COVID-19–associated lung failure.
JadiCell (Therapeutic Solutions International, Inc, Oceanside, California) is an MSC therapy under investigation to treat COVID-19 patients with severe complications of acute lung injury/acute respiratory distress syndrome (ALI/ARDS).
Severe COVID-19 may cause extensive, potentially fatal damage to lung tissue. COVID-19 ALI/ARDS is primarily characterized by a destructive, hyperinflammatory immune response to initial SARS-CoV-2 infection, which may persist and impair healing. An unmet medical need exists for effective therapies to improve patient outcomes in these instances.
JadiCell consists of donor-derived, allogeneic umbilical cord mesenchymal stem cells (UC-MSCs) expanded in number in laboratory cultures. MSCs suppress lung inflammation by reducing levels of the proinflammatory toll-like receptor 4 (TLR4) and increasing the Mer receptor tyrosine kinase (MerTK), an anti-inflammatory protein. JadiCell may augment scar tissue repair in the lungs as well as stimulate endogenous lung stem cells and the formation of new blood vessels. These effects could reduce lung damage, preserve lung function, and promote healing, potentially preventing respiratory failure and improving patient survival.
In the completed phase 1/2 clinical trial, 24 hospitalized adults with COVID-19 ARDS were given either 2 intravenous infusions of JadiCell or placebo 3 days apart. Results showed that treatment with MSCs was well tolerated and significantly improved patient survival (91% vs 42%) and time to recovery compared with standard-of-care treatment. In May 2022, the developer announced plans to conduct a phase 3, randomized, placebo-controlled clinical trial of JadiCell enrolling 128 patients with COVID-19–associated lung failure.
We were unable to find information regarding the cost of JadiCell. However, one clinic offering UC-MSC–based therapy in the Cayman Islands, a non-US territory, charges $25,000 for MSC therapy to treat COVID-19–associated lung failure outside of a clinical trial.
Effective treatments are needed to better mitigate lung damage in patients with severe COVID-19. JadiCell might help reduce inflammation and lung damage in these patients and improve health outcomes and survival.
Early feedback from ECRI stakeholders suggests that preliminary results from JadiCell are encouraging because it might prevent illness and death caused by COVID-19 respiratory complications, including lung inflammation, fibrosis, and impaired oxygen exchange.
Stakeholders thought the intravenous administration would facilitate integration of JadiCell into current patient management. Disparities in access might occur, however, as a result of staffing shortages, geographical availability, and high out-of-pocket expense. Additionally, diffusion might be limited by a lack of knowledge about the risks and benefits of the treatment. Education might be required for providers and patients, including a focus on mitigating any discomfort regarding the origin of the cells used in the therapy.
While the trial population did not explicitly address patients experiencing lingering respiratory symptoms after acute infection, JadiCell’s ability to restore decreased lung function suggests it might have potential for treating PASC.
Additional data and longer-term follow-up are needed to identify patients who might benefit from this treatment and to assess the impact of JadiCell on patient health outcomes.
- Categories: Treatment
- Areas of potential impact: Patient outcomes, health care costs, and health care disparities
mRNA-1273.214 to Prevent COVID-19
At a Glance
- The Omicron variant of SARS-CoV-2 and its increasingly prevalent subvariant, BA.2, have numerous spike protein mutations that decrease the effectiveness of currently available COVID-19 vaccines, contributing to increases in COVID-19 cases and hospitalizations worldwide.
- Moderna (Cambridge, Massachusetts) is investigating a bivalent messenger RNA (mRNA) vaccine, mRNA-1273.214, that targets the spike proteins on both the original virus and the Omicron variant to prevent COVID-19.
- Preliminary data analysis from a phase 2/3 trial found that mRNA-1273.214 increased antibody neutralization against Omicron and other variants in comparison with its predecessor.
- The company is preparing to submit data to regulators and is hoping to make the vaccine available for use in the fall of 2022 as a booster dose for those who have already been vaccinated with an approved or authorized COVID-19 vaccine.
The SARS-CoV-2 spike protein mediates virus entry into and subsequent infection of host cells. Currently available mRNA-based COVID-19 vaccines generate antibodies against the spike protein to block its function, which reduces incidence and severity of illness. However, this region of the virus is highly prone to mutation, and the emergence of SARS-CoV-2 variants, such as Omicron, has led to a decrease in vaccine effectiveness, even with the use of boosters.
mRNA-1273.214 is a lipid nanoparticle–encapsulated mRNA booster vaccine intended to protect against both the Omicron and earlier variants of SARS-CoV-2. mRNA-1273.214 combines the company’s currently authorized COVID-19 vaccine with an Omicron-specific booster candidate to create a bivalent vaccine. The vaccine’s mRNAs cause the person to produce both the altered Omicron viral spike protein as well as the spike protein of the original strain, inducing broader immune responses.
The bivalent vaccine is in a phase 2/3 trial with 3924 participants. Preliminary data showed that the vaccine had a superior neutralizing antibody response against the Omicron variant 1 month after administration when compared with the original Moderna vaccine and that it induced noninferior antibody responses against earlier variants. The bivalent booster was generally well tolerated, with a safety profile similar to the prototype booster. We were unable to find efficacy data reported for the bivalent vaccine. The developer is planning to submit the preliminary analysis to regulators in the coming weeks, aiming to make the vaccine available in the late summer or fall of 2022.
mRNA-1273.214 is given as a booster dose for individuals who completed their primary series and booster injections of an approved or authorized mRNA vaccine (ie, Moderna or Pfizer/BioNTech; New York, New York, and Mainz, Germany).
Decreased effectiveness of vaccines and boosters against the Omicron variant suggests the need for a bivalent booster vaccine to prevent and mitigate COVID-19.
Early feedback from ECRI internal stakeholders suggested that, if effective, mRNA-1273.214 could reduce the incidence and severity of illness due to COVID-19. This might improve patient health outcomes and reduce hospitalizations and deaths, especially as businesses are relaxing health restrictions and schools will likely operate in person in fall 2022.
Some people might hesitate to receive a new booster shot if the previous doses resulted in side effects such as fever, body aches, and headaches. mRNA-1273.214 might increase disparities for people who cannot take time off from work to recover from a COVID vaccine booster dose. The rise of new variants might also challenge the vaccine’s efficacy, resulting in decreased disruption. The bivalent vaccine’s impact will be influenced by how effective it is against Omicron versus how much the currently available vaccines or natural immunity protect people from Omicron or future variant exposure. mRNA-1273.214 might not significantly impact the general population’s health outcomes in a magnitude similar to the currently available vaccines.
- Categories: Treatment
- Areas of potential impact: Patient health outcomes, population health outcomes, health 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.
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: July 1, 2022
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