PCORI Biweekly COVID-19 Scan: Treatment for Post-COVID Conditions, Respiratory Syncytial Virus (RSV) Vaccines (December 8-21, 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.
According to the National Center for Health Statistics, 3544 death certificates for deaths occurring in the United States between January 1, 2020, and June 30, 2022, representing 0.3 percent of the 1,021,487 deaths with COVID-19 coded to U07.1 cited post-COVID condition (PCC or long COVID) as an underlying or contributing cause of death. The authors note that the data are provisional and subject to limitations, yet the numbers represent the first attempt to quantify who might be dying from PCC. PCC age-adjusted death rates were 7.3 per 1 million for males and 5.5 for females and appear to be highest for adults older than 85 years (117 per 1 million), and non-Hispanic American Indian or Alaska Native people (14.8 per 1 million).
The diverse symptoms that people with suspected PCC experience have created a diagnostic challenge. Machine learning analysis of over 137 symptoms and conditions found in electronic health record data from the National Patient-Centered Clinical Research Network (PCORnet, a PCORI-funded initiative) suggests PCC generally fall into 4 distinct types of disease manifestations: cardiac and renal; respiratory, sleep, and anxiety; musculoskeletal and nervous system; and digestive and respiratory system, following acute disease.
Preventing SARS-CoV-2 infection might be the only way to avoid PCC entirely. However, a recent literature review and meta-analysis of studies evaluating 1,600,830 individuals who had received at least 1 dose of Pfizer/BioNTech, Moderna, AstraZeneca, or Janssen vaccine found that vaccines were 35.3 percent effective against PCC if given before the person contracted COVID-19 and 27.4 percent if given afterward, relative to unvaccinated controls. So far this season we are facing a "tripledemic" of unprecedented rates of combined hospitalization due to respiratory syncytial virus (RSV), influenza, and COVID-19 that is overwhelming the healthcare system. Researchers continue to develop vaccines to mitigate the risks of respiratory illness. See Topics to watch for 2 investigational RSV vaccines.
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.
Combination Prednisolone and Losartan to Treat Post-COVID Conditions with Inflammatory Cardiac Involvement
At a Glance
- Research has shown that even mild cases of SARS-CoV-2 infection increase a patient’s risk for a wide range of long-term, post-COVID-19 conditions (PCCs). Cardiovascular symptoms, including shortness of breath, exercise intolerance, and chest pain are common.
- While inflammation has been identified as a likely contributing factor in the development and persistence of cardiovascular PCC, treatment options are limited, and no standard of care has been established.
- An ongoing phase 3 trial is testing whether prednisolone (a corticosteroid) combined with losartan (an angiotensin II receptor blocker) can reduce inflammation and enlargement of the heart following COVID-19 infection. Data are expected in December 2024.
- Both losartan and prednisolone have long been available in generic form. If effective, the combination treatment might offer an inexpensive, widely accessible oral therapy for patients suffering from cardiovascular PCC.
Long-term cardiovascular problems involving heart inflammation, ischemia, and blood clots are common after COVID-19. Symptoms include shortness of breath, exercise intolerance, and chest pain. Guidance on specific therapies to address PCCs linked to heart inflammation is still in development.
Researchers at Johann Wolfgang Goethe University Hospital (Frankfurt, Germany) are testing whether combination oral therapy with prednisolone and losartan can protect from inflammatory heart disease confirmed by magnetic resonance due to long-term complications after COVID-19 infection. Prednisolone is a corticosteroid widely used to reduce inflammation, and losartan is an angiotensin II receptor blocker used to treat hypertension that has also demonstrated effects in reducing heart enlargement in heart failure.
University researchers are evaluating this approach in the phase 3, randomized MYOFLAME-19 trial in collaboration with Bayer AG (Leverkusen, Germany) and Alcedis GmbH (Gießen, Germany). The study will enroll 280 patients aged 18 to 65 with documented recent COVID-19 infection (between 4 weeks to 6 months after acute infection), with diagnosed PCC and evidence of inflammatory cardiac involvement. The primary end point is change in left ventricular ejection fraction, a measure of heart function. Key secondary end points include changes in exercise capacity, left ventricular chamber size, and quality of life. The trial is scheduled to enroll 280 patients with a primary completion date of December 2024.
If the trial finds combination prednisolone-losartan effective at reducing cardiac inflammatory complications following COVID-19, the combination treatment might offer an inexpensive, oral therapy for patients suffering from cardiovascular PCC. Since we were unable to find reliable dosing information for this indication, we did not estimate the cost of treatment. But, we expect the treatment might be relatively inexpensive and widely available since both agents are available in generic form.
Cardiac inflammation after COVID-19 remains a long-term problem for many patients and effective treatments are needed to improve outcomes.
ECRI stakeholders noted that no standard of care has been established for treating PCC, and the health care system is struggling to understand and manage the condition. Studies like MYOFLAME-19 might improve our understanding of how SARS-CoV-2 infection affects the heart. An effective treatment for cardiac inflammation might reduce the risk of heart attack and myocarditis-induced heart failure, which in addition to improving individual outcomes could decrease burden on cardiac rehabilitation services.
Further, this treatment could diffuse quickly because it should be inexpensive, widely available, and appropriate for outpatients. Health disparities might decrease if more patients can equitably access and afford an effective treatment for cardiac inflammation. However, the treatment might be contraindicated for some patients, including those with kidney disease who are unable to take losartan and those for whom steroids would be detrimental.
- Category: Treatment
- Areas of potential impact: Patient health outcomes, population health outcomes, patient management, health care costs
Respiratory Syncytial Virus (RSV) Vaccines for Older Adults
At a Glance
- Respiratory syncytial virus (RSV) causes annual outbreaks of respiratory illness. Though symptoms are generally mild, community-dwelling adults aged 65 years and older, especially those with preexisting heart and lung conditions, are at heightened risk of life-threatening complications from severe RSV infection.
- Several vaccine candidates are in late clinical development to bolster immunity to RSV. These target RSV’s surface fusion (F) glycoprotein, specifically in its prefusion or “pre-F” state, which plays a critical pathogenic role in attaching to host cell membranes.
- RSV vaccines developed by GSK and Pfizer will be considered for FDA approval in May 2023, based on phase 3 results demonstrating significant reductions in RSV incidence and severity.
- We were unable to find information regarding the potential cost of these vaccines. However, a recent analysis suggests that an RSV vaccine with 50% efficacy and coverage similar to that of influenza vaccination might provide potential net economic gains between $557 and $1,024 million.
RSV is an easily transmissible, seasonal respiratory virus that typically produces mild, cold-like symptoms for most. RSV poses the most threat to young children and older age groups (aged ≥ 65 years) with weakened immune systems. Those with weakened immune systems or chronic heart (e.g., congestive heart failure) or lung disease (e.g., asthma or chronic obstructive pulmonary disease) are at greater risk of developing potentially life-threatening complications from severe RSV infection. According to the US Centers for Disease Control and Prevention (CDC), about 60,000 to 120,000 older adults in the United States are hospitalized, and 6,000 to 10,000 of them die due to RSV infection each year.
Several vaccine candidates designed to prevent or mitigate RSV infection in older adults are in late-stage clinical development. Most target RSV’s F glycoprotein because of the critical pathogenic role it plays in attaching to the surface of host cells, specifically in its “prefusion” (pre-F) conformation. Research has shown that natural immunity to RSV is derived primarily from antibodies recognizing the pre-F conformation of the protein.
RSV vaccines RSVPreF3 OA and PF-06928316 (RSVpreF) are currently being developed by GSK (Brentford, United Kingdom) and Pfizer (New York, New York), respectively. Phase 3 data for RSVPreF3 OA indicate overall vaccine efficacy of 82.6 percent against RSV lower respiratory tract disease (LRTD) and 94.1 percent efficacy against severe disease in adults aged 60 years and older. Phase 3 data for PF-06928316 indicate overall efficacy of 66.7 percent against RSV-LRTD and 85.7 percent efficacy against severe disease in adults aged 60 years and older. The FDA will evaluate both GSK’s and Pfizer’s vaccines for regulatory approval in May 2023.
We were unable to find information regarding the potential costs of these vaccines. However, a recent analysis estimates that an RSV vaccine with 50% efficacy and coverage matching that of influenza vaccination would prevent 43,700 to 81,500 RSV hospitalizations and 8000 to 14,900 RSV-attributable deaths per RSV season, resulting in a potential economic benefit of $557 to $1,024 million.
No licensed vaccine is currently available for treatment or protection against RSV, which every year causes serious illness in many vulnerable older adults.
ECRI stakeholders noted that RSV is a significant public health concern. Stakeholder feedback suggested that if RSV vaccines are approved and effective, they would likely reduce hospitalizations that result from severe RSV infections. The vaccines might reduce health care resource use, costs, and time health care professionals spend treating RSV-related complications. A vaccine might also reduce transmission in the community or in hospital settings, which could improve population health outcomes as well.
Stakeholders noted that vaccine development is costly and that before purchasing and distributing these vaccines to prevent surges, federal agencies must perform a risk-benefit analysis. However, cost-benefit analyses suggest that substantial patient and population health benefits as well as economic benefits could result. Stakeholders also expressed concern that, without effective outreach to counter antivaccine misinformation, uptake might be lessened.
- Category: Public health issues, vaccines and prophylaxis
- Areas of potential impact: Patient management, patient health outcomes, population health outcomes, health care costs, 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.
In May 2021, the COVID-19 supplement was modified and merged with the HCHSS. The Biweekly COVID-19 Scans continue, while the Status Reports and High Impact Reports were folded into the PCORI Horizon Scanning Database and High Potential Disruption Reports.
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 30, 2022
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