PCORI Biweekly COVID-19 Scan: Additional Dose of mRNA Vaccine, Post-Exposure Prophylaxis (August 5-18, 2021)
Briefing
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.
Caring for long COVID, or post-acute sequelae of COVID-19, is a prime example of patient-centered—or patient-defined—health care. These patients, often called long haulers, demonstrate that even mild COVID-19 can be life-altering. Moreover, research interest in post-viral syndromes and the possible connection to autoimmune diseases is gaining momentum because of strong patient advocacy. The large cohort of individuals experiencing long COVID represents a substantial data set that could reveal much about post-viral conditions and help many patients.
The risks of long COVID to the health care system are growing. Each new case, whether mild or severe, represents a possible patient with long COVID and now children are also reporting long COVID symptoms. If the proposed 10th edition of the International Classification of Diseases code for post COVID-19 is finalized for use in October 2021, there will be a more trackable prevalence rate. However, it is possible that many patients with long COVID will have left the health care system due to a lack of specialist centers located outside large urban areas.
A third vaccine dose for immunocompromised people and a new potentially preventive therapy for severe disease (see Topics to Watch) are 2 strategies that might ease the spread and the impact of the Delta variant of the coronavirus. These strategies could be of particular importance in high spread areas where health care facilities are often short-staffed.
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.
Additional Dose of mRNA Vaccine to Prevent COVID-19 in Individuals with Compromised Immune Systems
At a Glance
- A third dose of messenger RNA (mRNA)-based vaccine at least 28 days after the second dose might increase the immune response of COVID-19 vaccines to reduce infection spread, hospitalizations, and mortality rates in individuals with compromised immune systems.
- The eligible population can receive a third mRNA-based COVID-19 vaccine dose without a clinician referral or antibody testing. The Centers for Disease Control and Prevention (CDC) endorsed administering third doses of the same brand of mRNA vaccine given earlier to individuals with compromised immune systems. If the mRNA product administered for the initial vaccination series is unavailable or not known, then the patient may receive a different mRNA COVID-19 vaccine.
- Early evidence shows a third dose induces increases in antibody responses among a substantial proportion of persons who are immunocompromised.
- Some transplant recipients respond substantially better to current COVID-19 vaccines after the third dose. However, responses appear to be highly patient-specific.
- On August 12, 2021, the US Food and Drug Administration (FDA) expanded the Emergency Use Authorizations (EUAs) for a third dose of mRNA-based COVID-19 vaccines for individuals with compromised immune systems.
Description
The authorized COVID-19 vaccines were shown to be widely effective for the general population. However, persons with compromised immune systems were not included in vaccine trials and are at increased risk of poor outcomes. On August 12, 2021, the FDA expanded the EUAs for a third dose of mRNA-based COVID-19 vaccines for these individuals. Following this, the CDC endorsed third doses of the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine for these individuals, given as the same vaccine brand at least 28 days after the initial vaccination series. Patients can self-attest that they are immunocompromised to receive the additional dose, and these individuals should continue to follow current prevention measures (eg, wearing a mask, maintaining physical distance).
A case series on the safety and immunogenicity of a third vaccine dose in 30 individuals who are immunocompromised showed an increase in antibody levels in all study participants who had low-positive antibody titers after 2 doses and in one-third of participants with negative antibody titers after 2 doses. Results from this study suggest that receiving the same mRNA vaccine or a different type of mRNA vaccine as the third dose can induce substantial increases in antibody responses in individuals who are immunocompromised. The CDC recommends that if the mRNA product given to these individual for the initial vaccination series is unavailable or not known, then they may receive a different mRNA COVID-19 vaccine. As of August 19, 2021, individuals with compromised immune systems should not receive more than three mRNA doses.
In a study of 12 chronic dialysis patients without detectable antibodies after 1 dose, 5 (41.6%) given a third dose of mRNA vaccines were able to generate measurable antibody responses after the third dose. A French study showed that among the 59 solid-organ transplant recipients with undetectable antibodies after 2 doses, 44% generated detectable antibodies at 4 weeks after the third dose. A preprint observational cohort study of 75 maintenance hemodialysis patients suggests that patients with measurable spike protein-specific CD4+ T cells after the second dose could be more likely to benefit from a third dose of vaccine.
Commentary
An additional dose of mRNA vaccine might improve clinical outcomes for individuals who are immunocompromised. Taking concurrent immunosuppressive medications might continue to make some transplant recipients nonresponsive to a third dose. More studies are needed to identify which medications interfere with vaccine responses in order to effectively modify treatment regimens. New third-dose guidance might give some a false sense of security and cause individuals who are immunocompromised to relax their adherence to public health guidance (eg, masks, physical distance).
Early feedback from ECRI internal stakeholders suggests that a third vaccine dose for individuals with compromised immune systems might improve health outcomes at both individual and population levels. Increased antibody responses might help reduce the risk of COVID-19–related hospital admissions and reduce the burden on the health care system. Individuals with elevated immunity against the virus are less likely to transmit infection to other people, which improves population health outcomes and promotes a quicker return to normalcy. Stakeholders thought that administering a third dose might create disparities for underserved individuals due to barriers to care and transportation access.
Current evidence suggests that a third vaccine dose can stimulate sufficient neutralizing antibodies to protect previous nonresponders against COVID-19. However, concerns remain that some individuals might be hesitant to receive a third vaccine dose because of misinformation on social media platforms.
- Categories: Systems and management
- Areas of potential impact: Population health outcomes, disparities, patient health outcomes, patient management
Casirivimab and Imdevimab (REGEN-COV) Post-Exposure Prophylaxis to Prevent COVID-19–Related Complications
At a Glance
- Casirivimab plus imdevimab (REGEN-COV) is a combination monoclonal antibody therapy authorized for post-exposure prophylaxis of patients who are at high risk for progression to severe COVID-19 and are either immunocompromised or not fully vaccinated.
- REGEN-COV works by targeting the SARS-CoV-2 spike protein to prevent the virus from entering host cells and replicating, limiting the severity of exposure or infection.
- Recent phase 3 trial data found that REGEN-COV reduced the risk of symptomatic COVID-19 infection by 81% in individuals over the age of 12 who had household exposure to SARS-CoV-2.
- On August 10, 2021, the FDA revised the EUA for REGEN-COV for use as a post-exposure prophylaxis.
- REGEN-COV is free to patients, paid for by the US government, but depending on coverage, patients might pay for the cost of administration.
Description
Casirivimab plus imdevimab is a combination monoclonal antibody (REGEN-COV) (Regeneron Pharmaceuticals Inc, Tarrytown, New York) authorized for post-exposure prophylaxis of patients who are at high risk for progression to severe COVID-19 and are immunocompromised or not fully vaccinated (ie, people are considered fully vaccinated 2 weeks after their second dose in a 2-dose series or 2 weeks after the single-dose vaccine). This therapy is administered through intravenous infusion or subcutaneous injection and is intended to be delivered as soon as possible following suspected exposure to SARS-CoV-2 to improve health outcomes for patients and prevent progression to severe COVID-19, including hospitalization or death.
The 2 monoclonal antibodies comprising REGEN-COV target separate portions of the SARS-CoV-2 spike protein that typically interact with host cell receptors expressed in the body. Blocking this interaction prevents the virus from entering host cells and limits viral replication after exposure. Using 2 antibodies with distinct targets also purportedly decreases the likelihood that the virus mutates in a way that would render the therapy ineffective.
Results from a phase 3 trial in 1505 participants 12 years or older who were in contact with someone diagnosed with COVID-19 within 96 hours found that REGEN-COV reduced the risk of symptomatic COVID-19 infection by 81%. Overall COVID-19 risk reduction (symptomatic as well as asymptomatic) was 66% compared with placebo. No serious treatment-related adverse reactions were reported.
REGEN-COV was previously given EUA for treating mild to moderate COVID-19 and on August 10, 2021, the FDA revised the EUA for REGEN-COV for use as post-exposure prophylaxis. REGEN-COV remains authorized for use as a treatment in addition to post-exposure prophylaxis. REGEN-COV is free to patients, paid for by the US government, but depending on coverage, patients might pay for the cost of administration.
Commentary
Post-exposure prophylaxis with REGEN-COV might improve patient and population health outcomes by reducing the risk of severe COVID-19 in individuals who are immunocompromised or not fully vaccinated and have recently been exposed to SARS-CoV-2.
Early feedback from ECRI internal stakeholders suggested that REGEN-COV might be a useful option for patients who are not fully vaccinated or immunocompromised and have a suspected exposure to SARS-CoV-2. In addition, these individuals lack the typical vaccine-induced antibody levels needed to protect against COVID-19. By administering therapy before disease onset, it might improve patient outcomes by limiting the disease course.
Preventing severe disease might help reduce health disparities, mortality, and long-term complications of COVID-19. However, stakeholders had concerns that because the therapy is delivered in health care settings, it might increase disparities and might put others seeking health care at risk of infection. Monoclonal antibody therapies are costly, but the treatment might provide long-term cost savings if hospitalizations are avoided and fewer health care resources are needed. Uptake of REGEN-COV might still be limited by barriers affecting vaccine uptake, including fear of potential side effects, fear of needles, and lack of full approval by the FDA.
- Categories: Treatment and prophylaxis
- Areas of potential impact: Patient outcomes, health care disparities, health care costs
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: August 27, 2021
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