PCORI Health Care Horizon Scanning System: Horizon Scanning COVID-19 Supplement Status Report Volume 1, Issue 2
Prepared for: Patient-Centered Outcomes Research Institute 1828 L St., NW, Suite 900 Washington, DC 20036
Contract No. MSA-HORIZSCAN-ECRI-ENG-2018.7.12
Prepared by: ECRI 5200 Butler Pike Plymouth Meeting, PA 19462
Investigators: Randy Hulshizer, MA, MS Marcus Lynch, PhD, MBA Jennifer De Lurio, MS Brian Wilkinson, MA Damian Carlson, MS Christian Cuevas, PhD Andrea Druga, MSPAS, PA-C Misha Mehta, MS Prital Patel, MPH Donna Beales, MLIS Eloise DeHaan, BS Eileen Erinoff, MSLIS Cassia Hulshizer, AS Madison Kimball, MS Maria Middleton, MPH Diane Robertson, BA Kelley Tipton, MPH Rosemary Walker, MLIS Karen Schoelles, MD, SM
October 2020
Statement of Funding and Purpose This report incorporates data collected during implementation of the Patient-Centered Outcomes Research Institute (PCORI) Health Care Horizon Scanning System COVID-19 Supplement, operated by ECRI under contract to PCORI, Washington, DC (Contract No. MSA- HORIZSCAN-ECRI-ENG-2018.7.12). The findings and conclusions in this document are those of the authors, who are responsible for its content. No statement in this report should be construed as an official position of PCORI.
An innovation that potentially meets inclusion criteria might not appear in this report simply because the horizon scanning system has not yet detected it or it does not yet meet inclusion criteria outlined in the PCORI Health Care Horizon Scanning System: Horizon Scanning Protocol and Operations Manual COVID-19 Supplement. Inclusion or absence of innovations in the horizon scanning reports will change over time as new information is collected; therefore, inclusion or absence should not be construed as either an endorsement or rejection of specific interventions.
A representative from PCORI served as a contracting officer’s technical representative and provided input during the implementation of the horizon scanning system. PCORI does not directly participate in horizon scanning or assessing leads or topics and did not provide opinions regarding the potential impact of interventions. Financial Disclosure Statement None of the individuals compiling this information has any affiliations or financial involvement that conflict with the material presented in this report. Public Domain Notice This document is in the public domain and may be used and reprinted without special permission. Citation of the source is appreciated.
All statements, findings, and conclusions in this publication are solely those of the authors and do not necessarily represent the views of PCORI or its Board of Governors. This publication was developed through a contract to support PCORI’s work. Questions or comments may be sent to PCORI at [email protected] or by mail to 1828 L St, NW, Suite 900, Washington, DC 20036. ©2020 Patient-Centered Outcomes Research Institute. For more information see www.pcori.org.
Suggested citation: Hulshizer R, De Lurio J, Lynch M, et al. PCORI Health Care Horizon Scanning System: Horizon Scanning COVID-19 Supplement Status Report: Volume 1, Issue 2. Patient-Centered Outcomes Research Institute; October 2020. Prepared by ECRI under Contract No. MSA-HORIZSCAN-ECRI-ENG-2018.7.12.
HORIZON SCANNING SUPPLEMENT STATUS REPORT ● OCTOBER 2020 i
Preface 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 settings, 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 to have high impact on patient outcomes—for individuals and populations—in the United States in the next 12 months. The HCHSS COVID-19 Supplement produces 3 main outputs. Status Reports (every 4 months) 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, information technology professionals) have identified as having potential for high impact relative to COVID-19 in the United States. Biweekly COVID-19 Scans provide ECRI Horizon Scanning with a vehicle to inform PCORI, in a timely manner, of important topics of interest identified during ongoing scanning and topic identification or through the ECRI stakeholder survey process. For more information about the HCHSS COVID-19 Supplement outputs or the COVID-19- specific horizon scanning process, see the PCORI Health Care Horizon Scanning System: Horizon Scanning Protocol and Operations Manual COVID-19 Supplement. We welcome comments on this document. Send comments by mail to Patient-Centered Outcomes Research Institute, 1828 L St, NW, Suite 900, Washington, DC 20036, or by email to [email protected].
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Contents
Introduction ...... 1 Section 1. Devices: 13 Topics ...... 5 Table 1.1. Topics Added Since Last Status Report: 5 Topics ...... 5 Table 1.2. Currently Monitored Topics: 3 Topics ...... 9 Table 1.3. Recently Archived Topics: 5 Topics ...... 12 Section 2. Identifiable Risk Factors and Prognostic Indicators: 7 Topics ...... 14 Table 2.1. Topics Added Since Last Status Report: 5 Topics ...... 14 Table 2.2. Currently Monitored Topics: 1 Topic ...... 19 Table 2.3. Recently Archived Topics: 1 Topic ...... 20 Section 3. Screening and Diagnostics: 22 Topics ...... 21 Table 3.1. Topics Added Since Last Status Report: 10 Topics ...... 21 Table 3.2. Currently Monitored Topics: 5 Topics ...... 31 Table 3.3. Recently Archived Topics: 7 Topics ...... 36 Section 4. Systems and Management: 13 Topics ...... 40 Table 4.1. Topics Added Since Last Status Report: 5 Topics ...... 40 Table 4.2. Currently Monitored Topics: 5 Topics ...... 43 Table 4.3. Recently Archived Topics: 3 Topics ...... 47 Section 5. Treatments: 34 Topics ...... 48 Table 5.1. Topics Added Since Last Status Report: 16 Topics ...... 48 Table 5.2.Currently Monitored Topics: 17 Topics ...... 60 Table 5.3. Recently Archived Topics: 1 Topic ...... 74 Section 6. Vaccines and Prophylaxis: 9 Topics ...... 75 Table 6.1. Topics Added Since Last Status Report: 6 Topics ...... 75 Table 6.2. Currently Monitored Topics: 2 Topics ...... 81 Table 6.3. Recently Archived Topics: 1 Topic ...... 83 Appendix. Abbreviations and Acronyms ...... 84
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Introduction
The PCORI Health Care Horizon Scanning System (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 to have high impact on patient outcomes—for individuals and populations—in the United States within the next 12 months. COVID-19 Supplement Status Reports The PCORI HCHSS COVID-19 Supplement produces Status Reports every 4 months. The reports summarize key data elements for all COVID-19 topics monitored in the system and, if applicable, recently archived topics (typically those archived since the last Status Report). This Status Report is organized into 6 sections, titled as follows: (1) Devices, (2) Identifiable Risk Factors and Prognostic Indicators, (3) Screening and Diagnostics, (4) Systems and Management, (5) Treatments, and (6) Vaccines and Prophylaxis. An appendix lists the abbreviations and acronyms used in the report. Each of the 6 sections can contain 1 to 3 tables, depending on the topics included in that section: (1) topics added since the last Status Report, (2) currently monitored topics, and (3) recently archived topics. If no topics fall into a given category (ie, added, monitored, archived), then no table will be included for that category in that section. Tables for newly added and currently monitored topics summarize information in each row, as shown in the following columns: Title, Description, Possible areas of impact, and Possible future impacts. Tables of archived topics summarize information in each row, as shown in the following columns: Title, Description, and Archive reason. Within each table, topics are sorted alphabetically by title. ECRI Horizon Scanning has selected the topics included in this report 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, the accuracy of this information cannot be guaranteed after the date listed on this publication. Information presented in the Possible areas of impact and Possible future impacts columns solely represent prospective views of ECRI Horizon Scanning and have typically not been vetted by other stakeholders. These statements represent an ECRI horizon scanning analyst’s initial perspectives on a topic’s possible impacts. Analysts have been instructed, in the absence of hard data, to consider a topic’s possible areas of impact and possible future impacts in light of the developer’s claims (ie, if the product does what the developer claims, where might it have impact and what might be its possible future impacts?). Therefore, information presented in the Possible areas of impact and Possible future impacts columns should be considered prospective and may be updated, amended, or deleted when new information becomes available or after stakeholder review. No information in this report should be construed as an endorsement or rejection of any product listed in this report. Topics initially added to the system for monitoring may be archived after review of new data or after stakeholder review (see COVID-19 Supplement Horizon Scanning Process Overview: Monitoring, Updating, and Archiving Topics) when it appears that the topic does not have high
HORIZON SCANNING STATUS REPORT ● OCTOBER 2020 1
impact potential relative to COVID-19 in the United States in the next 12 months. An archived topic may reenter the system at a later date if new information comes to light suggesting that the topic has high impact potential. COVID-19 Supplement Horizon Scanning Process Overview The PCORI Health Care Horizon Scanning System: Horizon Scanning Protocol and Operations Manual COVID-19 Supplement (hereafter referred to as the Protocol) details the criteria we use to select topics. We briefly describe our process below.
Scanning, Lead Selection, and Topic Identification Scanners (ie, medical librarians and research assistants) collect COVID-19-related information leads from broad scanning and enter them into a leads database; they then categorize them according to content area (ie, devices, identifiable risk factors and prognostic indicators, screening and diagnostics, systems and management, treatments, and vaccines and prophylaxis) and subcategory, and link them, if applicable, to existing topics in the COVID-19 topics database. A research assistant assigns each lead to a horizon scanning analyst for review. Analysts review leads to discover potential topics. If a topic meets inclusion criteria, the analyst creates a new record in the COVID-19 topics database and enters a title and a description of the topic, possible areas of impact, and possible future impacts, which constitute the analyst’s rationale for proposing the topic. This information represents the analyst’s initial impressions of the topic prior to vetting with other stakeholders, and should be considered prospective. When populating the Possible areas of impact column, the analyst selects from the following terms (criteria for selection are listed after each term) based on her or his understanding of the currently available evidence or, in the absence of hard evidence, his or her theoretical extrapolation based on the developer’s claims: • Patient outcomes: This topic might impact health outcomes for an individual patient. • Population health: This topic might impact health outcomes across a group of individuals (eg, ethnicity, socioeconomic status, geographic area of residence, age). This is distinct from individual patient outcomes in that a particular intervention might impact individuals differently than it might impact populations (eg, a vaccine might carry certain risks to certain individuals but provide overall benefit to a population or populations). • Clinician and/or caregiver safety: This topic might impact, positively or negatively, the safety of a clinician or caregiver. • Health care delivery and process: This topic might impact the way health care is delivered to patients. • Health care disparities: This topic might increase or decrease health care disparities (ie, differences in the burden of disease or access to health care between different groups or populations). • Health care costs: This topic might substantially increase or decrease costs of care for patients, payers (ie, insurers), or health care providers. Each proposed topic is rapidly reviewed and voted on for inclusion by a preselected 3-person panel of PCORI HCHSS senior team members. A majority vote includes or excludes a topic accordingly. All included topics are reported in the Status Report. Each included topic undergoes content review and is then activated as a summary for the stakeholder review process.
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Stakeholder Review Process Topics are posted to an online bulletin board visible to a preselected panel of about 50 internal ECRI expert stakeholders (eg, physicians, nurses, allied health professionals, public health professionals, first responders, health systems experts, clinical engineers, researchers, business and finance professionals, information technology professionals). As topics are posted, stakeholders review them and complete an accompanying survey, which elucidates the stakeholder’s perspective on the topic’s potential for impact relative to the COVID-19 pandemic in the United States. The survey first prompts the stakeholder to indicate areas of potential impact, rating each area on a scale of 1 (no impact) to 4 (high impact). It then asks the stakeholder to rate the topic’s overall impact potential, timing of the impact, and likelihood of the impact on the same 1 to 4 scale. Finally, the stakeholder is asked to provide a brief written rationale explaining her or his selections and ratings. When a topic has received at least 5 completed surveys, it is eligible to be considered for inclusion in a High-Impact Report (see below); however, the questionnaire function remains active for all topics until the High-Impact Report selection process begins, allowing each member of the expert panel to comment on each topic as time permits.
High-Impact Report Topic Selection Every 4 months, all currently monitored topics that have received at least 5 completed stakeholder surveys are considered for inclusion in the High-Impact Report. The purpose of the selection process is to identify topics that stakeholders have deemed to have potential for high impact relative to COVID-19 in the United States. Generally, topics that stakeholders agree have a moderately high to high overall impact potential and are likely to have an impact within the next 12 months in the United States are selected for inclusion. However, stakeholder comments must generally support conclusions suggested by ratings. For topics with borderline ratings, high variance, or questionable comments, a brief review and vote by a preselected 3-person panel of senior horizon scanning team members determines inclusion or exclusion. A majority affirmative vote selects the topic for inclusion. See the Protocol for a detailed explanation of how we select topics for inclusion in the High-Impact Report.
Monitoring, Updating, and Archiving Topics Scanners use keywords and controlled vocabulary terms to monitor and search resources. When possible, scanners create automated alerts to capture new topic-specific information on an ongoing basis. These monitoring activities can trigger a change in topic status, depending on what has occurred. Analysts update topics as new information arises to ensure that the content is current. When a topic is updated, stakeholders who have commented on the topic are alerted to review the new information and revise or update their survey ratings and rationales, if desired. An included topic may be archived when new information overwhelmingly suggests that the topic is unlikely to cause significant impact relative to the COVID-19 pandemic in the United States in the next 12 months. Reasons may include one or more of the following: • Stakeholder ratings and comments strongly suggest that the topic does not have high impact potential. • New data do not support the developer’s claims relative to COVID-19.
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• Development has ceased or stalled. • The development timeline has shifted, and the product is no longer likely to be available within the next 12 months. Reporting Period Summary The PCORI HCHSS COVID-19 Supplement began operating in May 2020. Since then, review of about 1100 information leads has led to the identification and selection of 98 COVID- 19-related topics across the 6 content areas included in this Status Report, distributed as follows (also see Figure 1): • Devices: 13 topics (13%) • Identifiable risk factors and prognostic indicators: 7 topics (7%) • Screening and diagnostics: 22 topics (22%) • Systems and management: 13 topics (13%) • Treatments: 34 topics (35%) • Vaccines and prophylaxis: 9 topics (9%)
Note: Total does not equal 100% because of rounding.
Figure 1. Percentage of Topics by Content Area
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Section 1. Devices: 13 Topics
Table 1.1. Topics Added Since Last Status Report: 5 Topics
Title Description Possible areas of impact Possible future impacts
Isolation bags for safe CT Computed tomography (CT) scans can be used in alternative Population health Might increase the volume of patients imaging in suspected diagnostics or to guide management of COVID-19 complications. Clinician and/or caregiver who receive a chest CT in a more COVID-19 cases However, protecting patients and staff requires lengthy cleaning safety timely manner procedures between patients to adequately decontaminate imaging Might reduce staff exposure to equipment and examination rooms. An international team led by Health care delivery and process coronavirus by better isolating National Institutes of Health (NIH) researchers has developed a simple, patients during imaging inexpensive bag intended to safely isolate patients during CT scans. Health care costs The disposable isolation bag features breathing valves and is made Might reduce maintenance and from readily available, translucent (ie, almost clear) plastic material procedural costs if patient isolation commonly used to protect patients and imaging and surgical bags can safely avoid the need for equipment in other health care settings. The bag covers the head and some more intensive disinfection chest and is secured at the waist with a disposable elastic or Velcro procedures between imaging patients belt. Patients wear a hat with a visor to keep the bag off the face. Might cause some facilities to reduce Researchers estimate that use of this cost-saving and easily cleaning requirements below implementable isolation bag might allow about 14 times more recommended standards patients per day to undergo CT on a single CT scanner in a hospital Might cause anxiety in patients who emergency department. But the addition of another protective device already have difficulty breathing on top of personal protective equipment does not eliminate the recommendation for cleaning as part of standard infection control practices.
SECTION 1. DEVICES 5
Title Description Possible areas of impact Possible future impacts
Negative-pressure tents to Full-sized negative-pressure rooms can effectively contain the spread Clinician and/or caregiver Might increase the availability of limit airborne transmission of airborne pathogens, but the number of COVID-19 cases can safety negative-pressure environments to of coronavirus overload this resource. Compact negative-pressure patient tents Health care delivery and enhance protection for frontline might reduce the need for full-sized negative-pressure rooms, process health care providers decrease the risk of airborne transmission to frontline health care Health care costs Might reduce treatment costs of providers, and increase patient throughput. The tent is a portable providing negative-pressure unit placed at the top of the bed over the patient's head. Tents are environments compared with constructed of either clear, rigid plastic (resembling a box) with standard negative-pressure rooms hand-access ports or clear, soft plastic over a reusable frame (resembling a clamshell-like camping tent) with slits in the walls to allow provider access. A vacuum hose connected to the hospital air- evacuation system creates the negative-pressure environment. On June 13, 2020, FDA granted Oceanetics, Inc (Annapolis, Maryland), Emergency Use Authorization (EUA) for its NRSAVR-100 negative- pressure portable tent system to enhance personal barrier protection for providers during airway management, medical procedures, or transport of patients with COVID-19. University of Michigan researchers have developed a similar negative-pressure tent (Aerosolve) that the developers think might soon receive EUA for use during the COVID-19 pandemic.
SECTION 1. DEVICES 6
Title Description Possible areas of impact Possible future impacts
Nickel foam air filter to According to the US Environmental Protection Agency (EPA), indoor air Patient outcomes Might increase safety of indoor reduce the risk of is about 2 to 100 times more polluted than outdoor air because of the Population health spaces by reducing circulation of coronavirus transmission continuous circulation of particulates and bioaerosols (airborne airborne coronavirus, potentially particles of microbial, animal, or plant origin) within indoor spaces. Clinician and/or caregiver reducing risk of transmission in With the reopening of schools and businesses during the COVID-19 safety businesses, schools, and other pandemic, new methods of improving indoor air quality are needed. Health care costs enclosed environments Researchers at the University of Houston and collaborators developed Might increase risk of COVID-19 an air filter intended to remove airborne biothreats, including transmission if people stop following coronavirus. The proposed use of the filter is in air handling systems public health guidance (eg, social for central air conditioning units; however, researchers envision other distancing) owing to installation of uses, such as mobile personal air-purification devices to yield clean these air filters personal air space. The filter uses a nickel foam material that allows air to pass through its pores and is electrically conductive so that it can be heated up to 250°C. To maximize the energy efficiency of indoor air conditioning systems, the air filtration technology is heated internally, allowing minimal heat to escape to rooms. Tests conducted with this heated air filter found that 99.8% of coronavirus was effectively killed in a single pass. The True North Classical Academy (Miami, Florida) is deploying this air filtration technology to allow for safer school reopenings.
SECTION 1. DEVICES 7 Title Description Possible areas of impact Possible future impacts
Reusable silicone respirators Shortages of N95 respirators can increase risk of COVID-19 infection Clinician and/or caregiver Might help alleviate shortages of to protect against COVID-19 for frontline personnel. A team at the Massachusetts Institute of safety single-use N95 respirators for health infection Technology has designed a modular, reusable filtering facepiece Health care costs care providers and emergency respirator as an alternative to single-use N95 respirators. The new services responders during surges in silicone-based design purportedly can be mass-produced at a COVID-19 cases relatively low cost with standard injection molding manufacturing Might allow simpler reprocessing of techniques. The reusable mask, a tight-fitting, elastomeric respirator used respirators compared with that with a bidirectional filter, can be sterilized and reused multiple times of conventional single-use N95 while retaining its mechanical properties (ie, elasticity). The single-use respirators, which must meet certain filter insert is replaced during decontamination reprocessing. The eligibility requirements for safe developers have made the Open Standard Respirator, Model 1 design decontamination and reuse publicly available and are reportedly awaiting FDA approval for the mask, which entered production in the United States, Portugal, and Might help reduce personal other regions in June 2020. protective equipment (PPE) supply costs if reusable respirators can be mass-produced with standard manufacturing techniques
Robotic remote control of Mechanical ventilators supporting patients with COVID-19 may need Clinician and/or caregiver Might help conserve PPE if providers mechanical ventilators in multiple adjustments as the patients' respiratory needs change. safety can safely adjust ventilator settings intensive care units However, shortages of personal protective equipment (PPE) have Health care costs remotely without changing complicated efforts to manage the settings of multiple mechanically Might enhance provider safety if PPE ventilated patients in intensive care units while protecting frontline shortages are avoided providers moving between rooms. Johns Hopkins University researchers have developed a simple robotic system to control Might provide a future model for ventilator settings remotely. The robotic component is attached to a managing multiple isolated patients ventilator's touch screen and includes a camera that displays the who require mechanical ventilation ventilator screen on a wireless tablet for a remote user outside the Might lead to adverse events in cases patient room. The robot consists of 2 motors mounted on metal rods of operator or robot error that can move a stylus along the x and y axes. Users move the stylus to a location on the ventilator touch screen by touching the corresponding location on the image of the touch screen displayed on the remote tablet. Once the stylus is positioned, users can activate the stylus to press the ventilator touch screen, changing the ventilator settings. In early testing, investigators successfully used the system from an adjoining room to change the percentage and volume of oxygen delivered by a ventilator attached to a mannequin.
SECTION 1. DEVICES 8 Table 1.2. Currently Monitored Topics: 3 Topics
Title Description Possible areas of impact Possible future impacts
Decontamination systems Rapidly depleted supplies of N95 respirators for health care personnel Clinician and/or caregiver Might reduce shortages of N95 for reprocessing of single- have prompted several manufacturers to seek Emergency Use safety respirators for health care personnel use N95 respirators Authorization (EUA) from FDA for systems that purportedly Health care delivery and Might cost less than disposing of decontaminate N95 respirators designed for single use, allowing them process single-use respirators and purchase to be reused safely. A systematic review found that relatively few Health care costs of new respirators at inflated costs recent studies have assessed the safety and effectiveness of N95 during supply shortages respirator decontamination, and most available studies have examined the use of ultraviolet radiation for decontamination, among 21 Might raise safety concerns among different decontamination methods. As of September 17, 2020, FDA health care personnel if subsequent had granted 11 EUAs for the use of N95 respirator decontamination issues with respirator reprocessing systems during the COVID-19 outbreak. These systems typically arise employ vapor hydrogen peroxide or steam for decontamination of compatible N95 respirators that may be contaminated with SARS-CoV- 2 (severe acute respiratory syndrome coronavirus 2; the virus that causes COVID-19) or other pathogenic microorganisms. Most systems with EUAs are authorized for decontaminating N95 respirators for single-user use for 2 to 20 (clearly marked) decontamination cycles. In most cases, health care facilities ship used respirators to a manufacturer site for decontamination via special handling and shipping procedures. N95 respirators that contain cellulose material are incompatible with those decontamination systems that have EUAs thus far.
SECTION 1. DEVICES 9 Title Description Possible areas of impact Possible future impacts
Extracorporeal blood Early available data suggest that a major contributor to poor Patient outcomes Might improve patient outcomes by filtration to treat COVID-19 outcomes in patients with COVID-19 infection is a cytokine storm, an Health care delivery and avoiding or lessening severity of overly aggressive immune response to the pathogen that can process cytokine storm damage healthy tissue. Removing inflammatory mediators from Might require additional staff patients through an external blood filtering circuit has been experienced with extracorporeal proposed to lessen or prevent the cytokine storm. As of September blood filtration procedures 17, 2020, FDA had granted Emergency Use Authorization (EUA) to 4 manufacturers of extracorporeal blood filtration devices for use Might increase treatment complexity during the COVID-19 pandemic. When used with appropriate and necessitate additional patient systems (eg, apheresis systems, continuous renal replacement monitoring to quickly identify therapy systems), these devices purportedly remove inflammatory hematologic complications cytokines and, depending on the specific filter, pathogens from patients' blood. Extracorporeal blood filtration increases the risk of several complications, including bleeding, blood clots (thrombosis), air embolism, destruction of red blood cells (hemolysis), infection, low blood pressure (hypotension), and unintentional removal of other blood substances (eg, vitamins, minerals, proteins, medications).
SECTION 1. DEVICES 10 Title Description Possible areas of impact Possible future impacts
Transvenous phrenic nerve Prolonged mechanical ventilation can cause diaphragm muscle Patient outcomes Might improve patient outcomes by stimulation to improve atrophy, making ventilator weaning difficult. The Lungpacer Health care delivery and increasing successful ventilator ventilator weaning Diaphragm Pacing Therapy System is intended to reduce diaphragm process weaning attempts atrophy by stimulating the phrenic nerves, which control breathing Health care costs Might increase procedural costs for with the diaphragm. Physicians temporarily insert a single-use, disposable catheters and system multielectrode catheter into the left subclavian vein at the left shoulder control unit/pulse generators and advance it adjacent to the left and right phrenic nerves within the upper chest. Clinicians modulate electrical stimulation though the Might moderately reduce overall system's portable pulse generator and control unit. In May 2016, FDA treatment costs by preventing granted Lungpacer Medical, Inc (Vancouver, British Columbia, Canada), incidence of ventilator weaning Expedited Access Pathway (now Breakthrough Therapy) designation failures for the Lungpacer to treat patients unable to wean from ventilators. Might increase the need for specialist On April 14, 2020, FDA granted the developer Emergency Use staff experienced in placing Authorization (EUA) to assist in weaning patients deemed at high risk indwelling intravenous catheters, of weaning failure during the COVID-19 pandemic. The Lungpacer is to which might also increase exposure be used for no longer than 30 days. In a clinical trial of patients on risk and the need for personal mechanical ventilation for general indications for more than 4 days protective equipment (PPE) with 2 failed weaning attempts, patients receive 120 total daily Might increase patient monitoring stimulation repetitions, delivered in 2 daily sessions, for an unspecified requirements during temporary duration. electrode catheter placement
SECTION 1. DEVICES 11 Table 1.3. Recently Archived Topics: 5 Topics
Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Extracorporeal carbon dioxide COVID-19 can cause severe lung damage that requires intensive respiratory support. Low blood oxygen (hypoxia) is typically a more removal (Hemolung) to treat Extracorporeal carbon dioxide removal with the Hemolung Respiratory Assist System common concern than excess carbon dioxide COVID-19 lung failure has been developed as an alternative or supplement to mechanical ventilation, to (hypercapnia) in COVID-19. This intervention is treat acute respiratory failure in the intensive care unit. The dialysis-like circuit highly invasive, and its use will likely be limited to a purportedly removes carbon dioxide from the blood in a less invasive manner than very small group of COVID-19 patients. Thus, does extracorporeal membrane oxygenation (ECMO), in part by requiring smaller adoption and access would be quite low, greatly catheters and lower blood flows. However, the Hemolung system is not intended to limiting its overall disruptive potential. provide therapeutic levels of oxygenation. On April 22, 2020, FDA granted ALung Technologies, Inc (Pittsburgh, Pennsylvania), Emergency Use Authorization (EUA) for the Hemolung system to treat COVID-19-associated lung failure when used as an adjunct to noninvasive or invasive mechanical ventilation. The EUA authorizes Hemolung use to reduce hypercapnia and hypercapnic acidosis, or to maintain normalized levels of partial pressure of carbon dioxide and pH in patients suffering from acute, reversible respiratory failure for whom ventilation of carbon dioxide cannot be adequately, safely, or tolerably achieved.
Implantable diaphragm pacing Prolonged mechanical ventilation can cause diaphragm muscle atrophy, making The invasiveness of this procedure might increase (TransAeris) to improve ventilator weaning difficult. The TransAeris Diaphragm Pacing System is intended to infection risk in an already vulnerable population, ventilator weaning maintain diaphragm muscle strength by electrically stimulating the diaphragm with thus reducing uptake and disruptive potential. Less the intention of promoting more rapid weaning from mechanical ventilation. To aggressive use of mechanical ventilation for COVID- deploy the system, a surgeon uses a needle to temporarily implant 4 electrode leads 19 overall would further limit the diffusion of into the diaphragm, 2 on each side of the abdomen. The electrodes are tunneled implantable diaphragm pacing. through the skin and connected to an external pacing system that physicians program to deliver the electrical stimulation. The surgeon withdraws the implanted electrodes once the patient is successfully extubated after cessation of mechanical ventilation. On April 13, 2020, FDA granted Synapse Biomedical, Inc (Oberlin, Ohio), Emergency Use Authorization (EUA) for the device to help wean patients deemed at high risk of weaning failure during the COVID-19 pandemic, to be used for no longer than 30 days.
SECTION 1. DEVICES 12
Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Negative-pressure helmets to Negative-pressure environments offer health care providers an additional layer of Patients with breathing difficulty may resist wearing limit airborne transmission of protection against airborne pathogens, but their availability is limited during a a helmet, especially for extended periods, despite SARS-CoV-2) pandemic. University of Michigan researchers have developed a negative-pressure the potential benefit. Helmets might also complicate helmet (Aerosolve) intended to be worn by patients with COVID-19 to protect care (eg, oral medication delivery). Low patient providers while allowing patients some level of mobility. The helmet can facilitate acceptance would greatly diminish disruptive safe patient transport in an ambulance or within hospital departments. With the potential. helmet, health care providers can deliver supplemental oxygen with a heated high- flow nasal cannula, noninvasive ventilation, or nebulized medications. Developers anticipate receiving FDA Emergency Use Authorization (EUA) for the helmet during the current COVID-19 pandemic.
Noninvasive vagus nerve The vagus nerve is a major component of the autonomic nervous system that helps Lack of trial data on this intervention raises serious stimulation to treat COVID-19 regulate several involuntary bodily functions. ElectroCore, Inc (Basking Ridge, New questions about the feasibility or effectiveness of this Jersey), is evaluating whether its gammaCore noninvasive vagus nerve stimulator can approach. The long history and limited success of reduce the need for mechanical ventilation in patients with COVID-19. Hypothesized using vagus nerve stimulation devices to treat a mechanisms of vagus nerve stimulation include induction of bronchodilation or variety of different conditions raises further doubts reduction in inflammatory cytokines through activation of the cholinergic anti‐ about the treatment’s potential to disrupt the inflammatory pathway. In the trial, electrical stimulation is delivered to the vagus standard of care. nerve through the skin with a handheld stimulator placed against the neck 3 times per day and as needed for acute respiratory symptoms (eg, acute respiratory distress, shortness of breath). Secondary outcomes include change in supplementary oxygen use, cytokine trends, and change in survival.
Wearable physiologic monitors Patients with less severe symptoms of COVID-19 may be admitted to a hospital to High-risk patients should receive intensive to remotely observe patients allow for regular monitoring to detect rapid changes requiring more aggressive monitoring in a hospital. Because even mild cases of with COVID-19 intervention; however, this places a burden on hospital facilities in terms of COVID-19 may cause serious complications that occupancy levels and the requirement for additional anti-infection measures. require urgent treatment, measuring breathing, heart Wearable devices that collect physiologic data might allow for remote monitoring of rate, and temperature remotely might be insufficient lower-acuity patients in another health care setting or at home. Some available to prevent unexpected severe adverse events. Thus, systems (eg, Masimo SafetyNet) monitor and record a patient's blood oxygen remote monitoring would likely be limited to lowest- saturation, perfusion index, and respiration and pulse rate. Other monitors in risk patients, thereby limiting its overall disruptive development can sense respiratory symptoms, such as coughing or breathing potential. difficulty, and use artificial intelligence techniques to identify subtle changes that might indicate a future change in patient acuity that would require intervention.
SECTION 1. DEVICES 13
Section 2. Identifiable Risk Factors and Prognostic Indicators: 7 Topics
Table 2.1. Topics Added Since Last Status Report: 5 Topics
Title Description Possible areas of impact Possible future impacts
Artificial intelligence (AI)– Early identification of COVID-19 patients who may develop critical Patient outcomes Might assist health care professionals based assessment of clinical illness is of great importance and may aid in delivering proper Population health to make better treatment decisions data to determine COVID- treatment and optimizing use of hospital resources. AI algorithms Might help manage the surge of 19 prognosis based on assessment of patient clinical data are now being used to Clinician and/or caregiver safety patients requiring ventilators and assist with determining which patients may need intensive care. On alleviate the burden on health care May 26, 2020, FDA granted Emergency Use Authorization (EUA) for the Health care delivery and professionals and facilities CLEWICU system (CLEW Medical, San Francisco, California), which process Might help inform future triage assesses electronic health record data to help with the early Health care costs identification of patients who are likely to be diagnosed with paradigms respiratory failure or hemodynamic instability—common complications Might lead to inappropriate care in associated with COVID-19. Additionally, existing AI-based predictive cases of misclassification by the analytics systems are being used to assess patients with COVID-19. algorithm AlgoMarkers software by Medial EarlySign (Aurora, California) uses patient data from vital signs, lab test results, smoking history, and other medical history to help clinicians detect patients at increased risk of developing COVID-19 complications. The Deterioration Index by EPIC (Verona, Wisconsin) analyzes patients' data and calculates a risk score on a scale from 0 to 100, with a higher number signaling elevated concern that the patient's condition is deteriorating.
SECTION 2. IDENTIFIABLE RISK FACTORS AND PROGNOSTIC INDICATORS 14
Title Description Possible areas of impact Possible future impacts
Coronary artery calcification CAC can lead to chest pain, vasospasm, and increased risk of heart Patient outcomes Might better inform health care (CAC) as a prognostic factor attack. The presence of CAC on chest computed tomography (CT) Population health professionals of the potential need of for hospitalized COVID-19 scans might mark poorer COVID-19 prognosis, according to a French mechanical ventilation for patients patients cross-sectional study of 209 hospitalized COVID-19 patients aged 40 Health care delivery and process Might reduce costs by improving to 80 years with no history of cardiovascular disease. Chest CT scans utilization of hospital resources, but performed at hospital admission showed that 32% of patients younger it might also increase the cost of care than 62 years of age (n = 104) and 69% of patients aged 62 and older by adding an additional prognostic (n = 105) had CAC. Investigators found that, within 30 days of procedure hospitalization, 55% of patients younger than 62 years of age who had CAC experienced a first occurrence of mechanical ventilation, Might improve understanding of extracorporeal membrane oxygenation (ECMO), or death (primary COVID-19 pathogenesis composite outcomes) compared with 20% of patients who did not Might increase exposure risk to have CAC. In patients older than 62 years of age, one of these events health care workers and patients in occurred in 48% of those who had CAC compared with 13% who did CT suites not. Multivariate analysis led the investigators to postulate that CAC Might decrease throughput for other was significantly associated with the primary outcome. Determining CT procedures the presence of CAC in some hospitalized COVID-19 patients might aid in appropriately managing and monitoring the clinical course of their disease.
SECTION 2. IDENTIFIABLE RISK FACTORS AND PROGNOSTIC INDICATORS 15
Title Description Possible areas of impact Possible future impacts
Low maternal plasma Choline supplementation might protect fetal development and support Patient outcomes Might improve understanding of choline levels as a risk factor infant early behavioral development in the offspring of mothers who Population health COVID-19's effects during pregnancy for fetal brain development contract COVID-19, according to a study published by investigators Might reduce the prevalence of following COVID-19 from the University of Colorado School of Medicine. The study behavioral abnormalities in children infection reported that, among infants of mothers who had a viral respiratory infection during the first 16 weeks of pregnancy (n = 43), infants born to mothers with choline levels above 7.5 µM had significantly increased scores for attention and self-regulatory behavior on the Infant Behavior Questionnaire-Revised (IBQ-R) at 3 months of age compared with infants born to mothers who had lower gestational serum choline levels. Although this association has not been directly studied in pregnant women with COVID-19 infection, the investigators note that C-reactive protein (CRP) levels (a marker of inflammation) in women who experienced a respiratory infection were similar to CRP levels observed in pregnant Chinese women infected with COVID-19. Maternal inflammatory responses caused by viruses are thought to put offspring at increased risk for attention deficit/hyperactivity disorder, autism spectrum disorder, and schizophrenia. Maternal choline levels consistent with FDA's dietary recommendations for pregnancy purportedly decrease inflammation during maternal immune activation, potentially mitigating the adverse effects of inflammation on infant behavior. The researchers suggest that pregnant women maintain appropriate choline levels through dietary supplementation.
SECTION 2. IDENTIFIABLE RISK FACTORS AND PROGNOSTIC INDICATORS 16
Title Description Possible areas of impact Possible future impacts
Proton pump inhibitor use Investigators released preprint data from an online survey that Patient outcomes Might result in a change in PPI as a risk factor for revealed an independent, dose-response association between proton Population health dosage protocol COVID-19 pump inhibitor (PPI) use and positive COVID-19 test results. Among Might decrease the risk of SARS- 53 130 respondents, individuals taking PPIs once or twice daily had a Health care delivery and process CoV-2 infection among PPI users if significantly increased (2.15-fold and 3.67-fold, respectively) risk of dose modification is effective reporting a positive COVID-19 test result compared with participants not taking PPIs. The acidic environment of the stomach plays a key role Might improve understanding of the in the body's response to microbial infections. PPIs, a commonly pathogenesis of COVID-19 prescribed class of heartburn medications, raise the pH in the stomach by lowering acid production, which might increase susceptibility to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In vitro research published in August 2004 demonstrated that a pH below 3 (acidic) impaired the infectivity of SARS-CoV (severe acute respiratory syndrome–associated coronavirus), the virus responsible for the 2002 severe acute respiratory syndrome (SARS) outbreak, while a less acidic pH did not inactivate SARS-CoV. Additionally, people taking a less potent class of heartburn medication, histamine-2 receptor inhibitors, were not found to be at elevated risk for a positive COVID-19 test result. The investigators of the study suggest that clinicians use PPIs at the lowest indicated effective dose.
SECTION 2. IDENTIFIABLE RISK FACTORS AND PROGNOSTIC INDICATORS 17
Title Description Possible areas of impact Possible future impacts
Vitamin D deficiency as a Investigators reported data from 20 European countries indicating that Patient outcomes Might improve understanding of the risk factor for COVID-19 populations with lower average vitamin D levels were more likely to be Population health preventive role of vitamin D in diagnosed with COVID-19 as well as die from COVID-19. Vitamin D is COVID-19 an important factor in the immune system. It has been found to Health care delivery and process Might improve understanding of the protect against acute respiratory tract infections and its deficiency has population's susceptibility to COVID- been linked to increased susceptibility to viruses. Additionally, vitamin 19 D may beneficially modulate host immune responses to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). SARS-CoV-2 Might improve public health efforts infection leads to the release of inflammatory proteins, such as to decrease vitamin D deficiency in cytokines, that can lead to hyperinflammation known to contribute to the population severe COVID-19 and poor outcomes. Immune cells express vitamin D receptors that regulate hundreds of genes, including cytokines, and vitamin D deficiency purportedly increases cytokine production, potentially contributing to COVID-19-induced hyperinflammation. These mechanisms have led researchers to hypothesize that patients with vitamin D deficiency might be at a higher risk of developing COVID-19 or experiencing worse outcomes. A Canadian phase 3 randomized trial is comparing high-dose vitamin D supplementation with placebo in 2414 health care workers with a high risk of COVID-19 infection to determine if supplementation reduces the risk or severity of COVID-19 infection. The trial's estimated primary completion date is April 2021.
SECTION 2. IDENTIFIABLE RISK FACTORS AND PROGNOSTIC INDICATORS 18
Table 2.2. Currently Monitored Topics: 1 Topic
Title Description Possible areas of impact Possible future impacts
Interleukin-6 (IL-6) levels as Some COVID-19 patients have relatively mild symptoms, whereas Patient outcomes Might streamline patient triage based a prognostic factor in others develop severe disease. Additionally, the clinical course of Population health on the potential need for mechanical COVID-19 patients patients hospitalized for COVID-19 varies, and patients may deteriorate ventilation rapidly to respiratory failure, requiring ventilation and intensive care Clinician and/or caregiver safety Might reduce overall costs by unit admission. Research suggests that IL-6 levels might be a potential improving utilization of hospital biomarker of predicting severe COVID-19. Elevated IL-6 levels have Health care delivery and resources in some patients been associated with cytokine-mediated lung damage that can result in process Might increase overall costs if used severe respiratory distress in COVID-19 patients. Results from a clinical Health care disparities study conducted in hospitalized patients suggested that IL-6 levels inappropriately above 80 pg/mL are indicative of a high risk of respiratory failure. To Health care costs Might improve understanding of the that end, FDA has granted the Roche Diagnostics (Basel, Switzerland) pathogenesis of COVID-19 Elecsys IL-6 test Emergency Use Authorization (EUA) to help identify patients with confirmed COVID-19 who are at risk of intubation and mechanical ventilation. IL-6 testing is also available through multiple clinical laboratories (eg, ARUP Laboratorie, LabCorp , Quest Diagnostic).
SECTION 2. IDENTIFIABLE RISK FACTORS AND PROGNOSTIC INDICATORS 19
Table 2.3. Recently Archived Topics: 1 Topic
Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Smartphone application Six distinct clusters of symptoms might be used to better determine which patients with This technology is unlikely to be disruptive symptom tracking for COVID-19 are at higher risk for severe disease or might need respiratory support, according because it requires participants to consistently COVID-19 risk stratification to an analysis of data obtained from a symptom tracker app. A machine-learning algorithm update their symptoms, which may be a problem analyzed data from 1653 users who regularly logged their symptoms in the app, which was if the participants become too sick to continue then tested on an independent dataset of 1000 users across the United States, United logging symptoms. The symptoms described in Kingdom, and Sweden. Participants in cluster 6, the most severe symptom cluster that cluster 6 are well-known precursors to included abdominal and respiratory symptoms, were 13.2 times more likely to require hospitalization, lowering the clinical value of the respiratory support compared with participants reporting cluster 1 symptoms, the least app. severe cluster, including loss of smell, sore throat, and no fever. The free app analyzes user demographic information and symptoms reported over 5 days to determine which COVID- 19 symptom cluster best aligns with the user and helps predict risk of hospitalization and the need for respiratory support. Systems can also be put into place to alert individuals and primary health care teams if the patient displays symptoms associated with a high-risk cluster.
SECTION 2. IDENTIFIABLE RISK FACTORS AND PROGNOSTIC INDICATORS 20
Section 3. Screening and Diagnostics: 22 Topics
Table 3.1. Topics Added Since Last Status Report: 10 Topics
Title Description Possible areas of impact Possible future impacts
3D-printed nasopharyngeal As COVID-19 infections increased in the early months of 2020, the rapid, Population health Might improve testing availability by swabs for COVID-19 testing unprecedented demand for COVID-19 testing overwhelmed the supply Health care costs alleviating shortages of some testing chains of many health care facilities. One early impediment to accessories widespread availability of testing was a lack of testing accessories, Might reduce costs for testing including nasopharyngeal swabs to collect patient samples. To help supplies if more manufacturers are alleviate shortages, a consortium of researchers, health care providers, supplying nasopharyngeal swabs academic medical centers, and manufacturers collaborated to develop nasopharyngeal swabs comparable to commercially available swabs that could be produced in high volumes using 3-dimensional (3D) printing techniques. The consortium developed 4 prototypes and tested them for noninferiority against commercially available control swabs. At the study conclusion, investigators preferred one prototype over the other 3 and the control swab. The consortium developed the validated prototype in 22 days. The 3D-printed, FDA-registered test swabs with validated equivalent efficacy are available for order from manufacturers participating in the consortium.
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Title Description Possible areas of impact Possible future impacts
BinaxNOW COVID-19 Ag BinaxNOW COVID-19 Ag Card (BinaxNOW) is a lateral flow antigen Patient outcomes Might allow health centers to Card point-of-care antigen immunoassay developed by Abbott Diagnostics Scarborough as a Population health diagnose COVID-19 soon after a test to diagnose COVID-19 point-of-care (POC) test for use in settings including temporary patient arrives screening facilities, physician office laboratories, urgent care facilities, Health care delivery and process Might help triage infected and and long-term nursing facilities. BinaxNOW consists of a single-use uninfected patients on the same day card containing color-labeled antibodies that detect the coronavirus's Health care disparities they are tested nucleocapsid protein, which is detectable during the first 7 days of Health care costs symptom onset. A patient's nasal swab is inserted into a small test card Might be more affordable than tests along with an extraction reagent that exposes the viral nucleocapsid. performed in central laboratories Test results are read on the card like a pregnancy test, with one line Might increase the rate of false- indicating a negative result and 2 lines indicating a positive result. negative test results if the assay does Results can be sent to a mobile device app (NAVICA), which can be not detect very low levels of viral used as a temporary digital health pass that is renewed each time an nucleocapsid proteins individual is tested. The manufacturer claims that each $5 BinaxNOW card yields results in about 15 minutes. In August 2020, FDA granted BinaxNOW Emergency Use Authorization (EUA). In a study that served as the basis of the EUA, BinaxNOW's performance was evaluated in 102 nasal samples that were also tested with an EUA reverse transcriptase polymerase chain reaction (RT-PCR) assay. BinaxNOW had a sensitivity of 97.1% and a specificity of 98.5%.
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Title Description Possible areas of impact Possible future impacts
College and university College and university COVID-2 testing programs are services offered Patient outcomes Might help faculty, staff, and SARS-CoV-2 testing by clinical laboratories (eg, Quest Diagnostics [Secaucus, New Jersey], Population health students feel safe about returning to programs to prevent Laboratory Corporation of America Holdings [LabCorp, Burlington, college or university Health care disparities COVID-19 spread among North Carolina], Bio-Reference Laboratories, Inc [Elmwood Park, New Might catch COVID-19 cases in the returning students Jersey], and Color Genomics, Inc [Burlingame, California]) intended to Health care costs campus early and thus help quickly limit SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) suppress spread of the virus spread and boost student confidence about returning to campus. Schools implementing a testing program may give all returning Might create supply shortages via students, faculty, and staff a SARS-CoV-2 molecular test along with an frequent testing in large campus antibody test at the beginning of the school year, with several levels of populations surveillance throughout the year. This will help schools assess a Might create disparities in colleges baseline for their community, understand the prevalence of the virus and universities where these testing on campus, and make decisions on quarantines and other distance programs are not available measures for the population returning to campus. Schools may provide Might cause the virus to initially self-collection kits to avoid overwhelming health centers and clinical spread undetected if test results yield laboratories. Upon receiving samples, central laboratories will have test high false negatives results available through an online platform in about 3 to 5 days. College and university testing programs have potential to detect Might increase the rate of false- COVID-19 cases early and prevent coronavirus from spreading among negative test results if students using students. a self-collection kit do not acquire a proper specimen with detectable virus Might be difficult to triage students if it takes days for test results to become available
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Title Description Possible areas of impact Possible future impacts
CRISPR-based SARS-CoV-2 Clustered regularly interspaced short palindromic repeats (CRISPR)– Patient outcomes Might deliver comparable test results assays to diagnose based assays, such as Sherlock (Sherlock Biosciences, Inc) and DETECTR Population health quicker than polymerase chain COVID-19 (Mammoth Biosciences, Inc), are intended to diagnose COVID-19 by reaction (PCR)–based assays detecting SARS-CoV-2 (severe acute respiratory syndrome coronavirus Health care delivery and process Might decrease costs by allowing 2) nucleic acids. These assays employ a loop-mediated isothermal laboratories to process hundreds of amplification reaction to intensify nucleic acids in the sample. The Health care disparities patient samples per day products of this amplification reaction are exposed to an RNA-guided nuclease (eg, Cas12a, Cas13a) that becomes activated only in the Might increase the rate of false- presence of SARS-CoV-2 nucleic acids. If activated, the nuclease negative test results if the assay does cleaves a fluorophore-labeled reporter nucleic acid. Depending on the not detect very low levels of viral reporter technology used, reporter cleavage is measured by nucleic acids fluorimeter or lateral flow assay. CRISPR-based assays can purportedly Might create disparities for patients detect the presence or absence of SARS-CoV-2 nucleic acids within an who do not have access to health hour in a highly specific way. FDA has granted Emergency Use centers and laboratories that offer Authorization (EUA) to the Sherlock SARS-CoV-2 kit and the SARS- CRISPR-based testing CoV-2 RNA DETECTR Assay for use in laboratories certified by the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Sherlock Biosciences and Mammoth Biosciences are also developing CRISPR- based diagnostic tests for use in the point-of-care (POC) and/or consumer use settings. A preprint study evaluating DETECTR's performance in 378 samples previously tested by reverse transcriptase polymerase chain reaction (RT-PCR) reported 94.9% concordance between both assays. The study also reported that results from the POC version of DETECTR were 100% concordant with those from the EUA version of DETECTR.
SECTION 3. SCREENING AND DIAGNOSTICS 24
Title Description Possible areas of impact Possible future impacts
Employee COVID-19 testing Employee COVID-19 testing programs offered by clinical laboratories Patient outcomes Might help employees feel safe programs to reopen (eg, Quest Diagnostic; Laboratory Corporation of America Holdings Population health about returning to their workplace businesses [LabCorp]; Bio-Reference Laboratories, In; and Color Genomics, In) are Health care disparities Might catch COVID-19 cases in the intended to limit novel coronavirus spread in the workplace and boost workplace early and thus help quickly confidence that employees can return to a safe work environment. Health care costs suppress spread of the virus Testing programs emphasize operating under simple and streamlined conditions that allow COVID-19 cases to be caught early and prevent Might create disparities in regions disease spread. COVID-19 testing programs might incorporate where employee testing programs unreliable screening methods, including health questionnaires and are not available temperature screening, or more reliable screening methods, such as Might cause the virus to initially nucleic acid testing, either at the employer site or offsite using an at- spread undetected if test results yield home self-collection kit. Pilot programs (eg, Quest Diagnostics, high numbers of false negatives LabCorp) have used tests performed at central laboratories that Might create supply shortages via provide results within 2 to 5 days after receiving the sample. The frequent testing in large corporate employer and employee have access to test results through an online populations platform. While point-of-care (POC) tests offer same-day test results, they are currently not being used because of recent concerns about Might be difficult to triage their higher false-positive and false-negative rates than central employees if it takes days for test laboratory tests. results to become available
SECTION 3. SCREENING AND DIAGNOSTICS 25
Title Description Possible areas of impact Possible future impacts
Isothermal amplification The BioFrontiers Institute and University of Oxford are developing Patient outcomes Might help suppress spread of assays to test for COVID-19 isothermal amplification assays that provide a low-complexity and Population health COVID-19 by triaging infected and in community or field portable way to amplify viral nucleic acids in community and field uninfected individuals on the same settings settings, including temporary screening facilities, hospitals, long-term Clinician and/or caregiver day they are tested safety nursing facilities, schools, universities, companies, and airports. These Might be more affordable than POC assays require only sample collecting kits, pipettes, a heating source Health care delivery and tests and those performed in central (eg, water bath, heat blocks), and tubes containing amplification process laboratories reagents. Isothermal amplification assays purportedly require a small Health care disparities sample volume and minimal hands-on time to yield laboratory-quality Might create disparities in regions results in approximately 45 minutes, and their low complexity might Health care costs where community and field testing allow tests to be performed by non–health care professionals. programs are not available Individuals who test positive would be recommended to undergo Might cause the virus to initially confirmatory testing and self-quarantine. In addition to these spread undetected if test results yield investigational assays, FDA has granted 5 isothermal amplification- high numbers of false negatives based assays Emergency Use Authorization (EUA) in central laboratories or point-of-care (POC) settings, and these tests could eventually become authorized for screening in community and field settings.
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Title Description Possible areas of impact Possible future impacts
Next-generation sequencing Several next-generation sequencing (NGS) assays have been Patient outcomes Might enable laboratories to process assays to diagnose COVID- developed to diagnose COVID-19, including COVIDseq (Illumina, Inc), Population health thousands of patient samples per day 19 CleanPlex SARS-CoV-2 (Paragon Genomics, Inc), COVID-19 NGS test Might allow screening for COVID-19 (Fulgent Genetics, Inc), Guardant-19 (Guardant Health, Inc), and Helix Health care delivery and process in the general population, as well as COVID-19 NGS test (Helix OpCo, LLC). These assays may be performed diagnosing the disease in only at laboratories certified by the Clinical Laboratory Improvement Health care disparities symptomatic individuals Amendments of 1988 (CLIA), including central laboratories and some Health care costs laboratories at hospitals, research institutions, and academic Might be more expensive than institutions. These assays employ deep sequencing (ie, a genetic standard testing performed in central sequencing technique that requires only a very small sample) and laboratories and in point-of-care computational methods to detect nucleic acids of the coronavirus. (POC) settings Tests can amplify and detect sequences from the whole viral genome Might create disparities for patients (ie, a string of about 30 000 nucleic acids) or several genomic regions. who do not live near health centers NGS assays purportedly offer high throughput, enabling 2000 to 3000 with capabilities and certifications to samples to be processed in about 12 hours, with comparable accuracy offer NGS testing to standard polymerase chain reaction (PCR) tests. These assays might also be used in epidemiology studies to track the spread of coronavirus or to screen individuals who are planning to return to work or school. FDA has granted Emergency Use Authorization (EUA) to COVIDseq, Guardant-19, and Helix COVID-19 NGS test.
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Title Description Possible areas of impact Possible future impacts
Population-wide antibody The COVID-19 pandemic has caused substantial public health and Patient outcomes Might inform actual infection rates testing to quantify economic crises, which makes testing for the prevalence of coronavirus Population health and more accurately track the spread coronavirus infection rates infection, as well as potential immunity, critical to measure the spread of coronavirus of the disease. Medicare beneficiaries who may be at greater risk of Clinician and/or caregiver safety Might misinform public health serious COVID-19 can get an antibody test at no cost. Testing for guidance if the employed serology coronavirus-specific antibodies in the blood of individuals has the Health care delivery and tests generate high numbers of false potential to identify persons who have been exposed to the virus process positives or false negatives regardless of whether they developed symptoms, and widespread Health care disparities serosurveys have the potential to provide data on the extent of COVID- Might misrepresent true infection 19 spread. The Centers for Disease Control and Prevention (CDC) is Health care costs rates by depending on blood donors, conducting a country-wide COVID-19 study that will test blood who are disproportionately healthy samples of up to 325 000 donors in 25 selected cities over the course and may not be the ideal population of 18 months. A nonprofit blood service provider, Vitalant, will be to evaluate the spread of coronavirus partnering with the CDC and the National Institutes of Health (NIH) to infection collect samples for this serologic study. The NIH also launched a similar study of 15 000 participants with no known coronavirus infection or exposure. The NIH is collecting blood samples from employee volunteers at its Bethesda campus and using at-home blood collection kits developed by Neoteryx (Torrance, California) from other volunteers.
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Title Description Possible areas of impact Possible future impacts
Rapid point-of-care breath Researchers at Ben-Gurion University of the Negev (Beer-Sheva, Israel) Patient outcomes Might enable more rapid POC testing test to detect COVID-19 have developed an inexpensive point-of-care (POC) test that Population health in public areas, such as airports or purportedly detects COVID-19 in samples of breath from both businesses, to facilitate economic symptomatic and asymptomatic carriers in less than 1 minute with Health care costs reopening greater than 90% accuracy. To test for COVID-19, a subject breathes Might help slow the spread of into a whistle-like tube that holds an electronic chip containing COVID-19 if more asymptomatic thousands of electro-optical sensors, housed in a removable capsule. carriers are identified sooner The capsule is then placed in a small spectrometer connected to a laptop computer that transmits data for cloud-based mathematical Might improve consumer confidence analysis. The system measures resonance changes in the terahertz in public health efforts through spectral range specific to SARS-CoV-2 (severe acute respiratory simple, rapid, and effective POC syndrome coronavirus 2). Results are automatically recorded into a testing database that public health authorities can use to track viral spread. In preliminary tests, the POC test matched polymerase chain reaction (PCR) swab test results in 93.3% of tests performed. Researchers estimate test kits will cost about $50, with each system running about 4000 tests per day. Developers are seeking FDA approval and anticipate starting production of the POC testing system by October 2020. Another team, at Technion Israel Institute of Technology (Haifa, Israel), has developed a breathalyzer-like POC system that purportedly detects COVID-19-specific volatile organic compounds in exhaled breath.
SECTION 3. SCREENING AND DIAGNOSTICS 29
Title Description Possible areas of impact Possible future impacts
Saliva-based nucleic acid Saliva-based nucleic acid assays, such as CRL Rapid Response (Clinical Patient outcomes Might reduce the risk of assays to diagnose Reference Laboratory, Inc), SalivaDirect (Yale School of Public Health), Population health transmitting SARS-CoV-2 to medical COVID-19 and TaqPath SARS-CoV-2 (Rutgers Clinical Genomics Laboratory), are staff and other patients, if sample used to diagnose COVID-19 by detecting SARS-CoV-2 (severe acute Clinician and/or caregiver collection is performed at home, respiratory syndrome coronavirus 2) nucleic acids from a patient's safety and help triage infected and saliva sample. Compared with traditional sampling using Health care delivery and uninfected patients nasopharyngeal swabs, saliva sampling is less invasive, costs less, and process Might decrease costs associated can be performed at home or at a health center without the Health care disparities with sample collection and ease the supervision of a health care worker. Some saliva-based assays have Health care costs burden at testing sites with limited been validated to use minimally processed saliva samples, obviating personal protective equipment (PPE) the need for a nucleic acid extraction step, which might save time and and testing supplies testing supplies. A rapid systematic review demonstrated that saliva- based nucleic acid testing yields similar outcomes as nasopharyngeal Might increase the rate of false- swab-based nucleic acid testing. FDA has granted Emergency Use negative test results if assays testing Authorization (EUA) to CRL Rapid Response, SalivaDirect, and TaqPath saliva do not detect viral nucleic SARS-CoV-2 for use in laboratories certified under the Clinical acids at all stages of infection Laboratory Improvement Amendments of 1988 (CLIA). The EUAs for Might create disparities for patients CRL Rapid Response and TaqPath SARS-CoV-2 allow samples to be who do not live near health centers collected by patients in the home setting. with capabilities and certifications to offer saliva-based testing
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Table 3.2. Currently Monitored Topics: 5 Topics
Title Description Possible areas of impact Possible future impacts
Accula SARS-CoV-2 point- The Accula SARS-CoV-2 test is a polymerase chain reaction (PCR) assay Patient outcomes Might enable health centers to of-care test to diagnose developed by Mesa Biotech, Inc (San Diego, California), as a point-of- Population health diagnose COVID-19 soon after a COVID-19 care (POC) COVID-19 test. It is intended for use in temporary screening symptomatic patient arrives at a facilities, physician office laboratories, urgent care facilities, and long- Health care delivery and health center process term nursing facilities. The Accula system consists of a single-use Might help triage infected and cassette that contains the reagents needed to amplify viral nucleic Health care costs uninfected patients on the same day acids. Using nasal and throat swabs, the sample is added into the they are tested cassette and then is placed in the Accula Dock. The dock is a palm- sized device that controls reaction temperatures, timing, and fluid Might be more affordable than tests movement within the cassette. At the end of the reaction, results performed in central laboratories indicating whether viral nucleic acids have been detected in the patient Might increase the rate of false- sample are displayed on the side of the cassette. The Accula system negative test results if the assay does purportedly yields laboratory-quality results in about 30 minutes and is not detect very low levels of viral intended to complement central laboratories, where most current nucleic acids testing is performed. In March 2020, FDA granted the Accula SARS- Might not be broadly available in all CoV-2 test Emergency Use Authorization (EUA). A published study health centers evaluated the performance of the Accula SARS-CoV-2 test in 100 nasopharyngeal samples previously tested by the SARS-CoV-2 PCR Assay, an EUA test developed by Stanford Health Care Clinical Virology Laboratory (Palo Alto, California). The Accula SARS-CoV-2 test had a sensitivity of 68%, a specificity of 100%, and an overall percentage agreement of 84%.
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Title Description Possible areas of impact Possible future impacts
COVID-19 at-home self- The at-home COVID-19 self-collection test kit consists of a nasal cotton Patient outcomes Might reduce risk of transmitting collection kits swab or saliva collection tube, a biohazard specimen bag, and an Population health SARS-CoV-2 to medical staff and overnight shipping envelope. The kit permits at-home collection of a other patients sample appropriate to perform a SARS-CoV-2 (severe acute respiratory Clinician and/or caregiver safety Might reduce the need for PPE in syndrome coronavirus 2) nucleic acid–based molecular diagnostic test testing departments for individuals with COVID-19 symptoms or for those who have had Health care delivery and possible exposure to the virus. The self-collection kit purportedly process Might increase testing in people with barriers to care reduces the risk of infected individuals transmitting the virus to others. Health care disparities Because the test kit does not require a clinician to collect a nasal or Might increase the rate of false- saliva specimen, it might also reduce the demand for personal negative test results if the patient protective equipment (PPE). On average, nasal swab self-collection kits does not acquire a proper specimen cost about $115 each and saliva collection kits cost between about $10 with detectable virus and $100 each. Out-of-pocket costs may be waived for individuals Might limit whether the sample is deemed eligible by a survey or reimbursed at the discretion of the safely shipped to a testing facility patient's health insurance. FDA has granted Emergency Use Authorization (EUA) to the COVID-19 self-collection test kit (Laboratory Corporation of America Holdings, Burlington, North Carolina), COVID- 19 test home collection kit (EverlyWell, Inc, Austin, Texas), Oragene Dx OGD-510 kit (DNA Genotek, Inc, Ottawa, Ontario, Canada), and SDNA- 1000 Saliva Collection Device (Spectrum Solutions, LLC, Draper, Utah).
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Title Description Possible areas of impact Possible future impacts
CoviTact point-of-care CoviTact is a coronavirus protease detection assay developed by Patient outcomes Might allow the detection of very low protease assay to diagnose ViroTact BV (Groningen, the Netherlands), a subsidiary of Detact Population health levels of SARS-CoV-2 particles COVID-19 Diagnostics BV (Groningen, the Netherlands), as a point-of-care (POC) Health care delivery and Might detect COVID-19 infection COVID-19 test. It is intended to be used in temporary screening quicker than nucleic acid–based tests facilities, physician office laboratories, urgent care facilities, and long- process term nursing facilities. CoviTact consists of a short peptide that is Health care costs Might be more affordable than bound to a near-infrared light (NIRL)–emitting molecule and a nucleic acid–based tests quencher molecule that absorbs NIRL. The peptide has been designed Might increase the rate of false- to contain a specific amino acid sequence that can be recognized and negative test results if the assay does cleaved only by the SARS-CoV-2 (severe acute respiratory syndrome not emit detectable NIRL in the coronavirus 2) main protease (Mpro). Once Mpro cleaves the peptide, the presence of very low levels of Mpro NIRL-emitting molecule is no longer in close proximity to the quencher molecule and NIRL can be detected using a fluorimeter. CoviTact can purportedly detect SARS-CoV-2 in saliva samples, nasal swabs, or other possibly infectious bodily fluids. If Mpro is present in a patient sample, CoviTact purportedly confirms COVID-19 cases within minutes in a highly specific way.
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Title Description Possible areas of impact Possible future impacts
QIAstat-Dx Respiratory The QIAstat-Dx Respiratory SARS-CoV-2 Panel, a real-time Patient outcomes Might enable health centers to SARS-CoV-2 Panel test to polymerase chain reaction (PCR) assay (Qiagen, NV, Hilden, Germany), Population health diagnose COVID-19 soon after a diagnose COVID-19 is intended to diagnose COVID-19 and differentiate it from 20 other patient arrives and determine causes of respiratory infection. The test is authorized to be used in Health care delivery and whether symptoms are caused by laboratories certified under the Clinical Laboratory Improvement process SARS-CoV-2 or a different infectious Amendments of 1988 (CLIA). The panel consists of a single-use Health care disparities agent cartridge that includes all reagents needed for nucleic acid extraction, Health care costs Might help triage infected and nucleic acid amplification, and detection of 3 bacteria and 18 viruses uninfected patients on the same day (or their subtypes), including SARS-CoV-2 (severe acute respiratory they are tested syndrome coronavirus 2), that cause respiratory symptoms. Using nasopharyngeal swabs, the sample is added into the cassette, which is Might be more affordable than tests then placed in the QIAstat-Dx Analyzer 1.0. The real-time PCR assay performed in central laboratories should be performed only by laboratory professionals trained in the Might increase the rate of false- use of QIAstat-Dx Analyzer 1.0. At the end of the reaction, results negative test results if the assay does indicating whether pathogen nucleic acids have been detected in the not detect very low levels of viral patient sample are displayed on the analyzer’s screen. The panel nucleic acids purportedly requires a small sample volume and minimal hands-on Might create disparities for patients time, and the results are available in about 1 hour. In March 2020, who do not live near health centers FDA granted the QIAstat-Dx Respiratory SARS-CoV-2 Panel with capabilities and certifications to Emergency Use Authorization (EUA). A published study evaluated the offer the test performance of the panel for detecting SARS-CoV-2 in 69 samples previously tested by a reverse transcriptase PCR test recommended by the World Health Organization (Geneva, Switzerland). QIAstat-Dx had a sensitivity of 100%, a specificity of 93%, and an overall agreement of 97%.
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Title Description Possible areas of impact Possible future impacts
Sofia 2 SARS Antigen FIA The Sofia 2 SARS Antigen Fluorescent Immunoassay (FIA) was Patient outcomes Might enable health centers to point-of-care test to developed by Quidel Corp (San Diego, California) as a SARS-CoV-2 Population health diagnose COVID-19 soon after a diagnose COVID-19 (severe acute respiratory syndrome coronavirus 2) antigen detection patient arrives at a health center and assay. It is intended for point-of-care (POC) use in settings such as Health care delivery and determine whether symptoms are temporary screening facilities, ambulatory care centers, and long-term process caused by SARS-CoV-2 or a different nursing facilities. The Sofia 2 SARS FIA is a cassette-based lateral flow Health care costs infectious agent immunoassay that detects the nucleocapsid protein from SARS-CoV Might help triage infected and (severe acute respiratory syndrome–associated coronavirus) and SARS- uninfected patients on the same day CoV-2 (the virus that causes COVID-19), using antibodies. After a nasal they are tested or nasopharyngeal swab is treated with a solution that exposes the viral nucleocapsid, the sample is added to the cassette and placed in the Might be more affordable than tests Sofia Analyzer. The analyzer reads the cassette and reports whether performed in central laboratories viral antigen was detected in the patient sample. The Sofia 2 SARS FIA Might not be broadly available in all purportedly requires a small sample volume and minimal hands-on health centers time, and the results are available in about 10 minutes. In May 2020, Might increase the rate of false- FDA granted Emergency Use Authorization (EUA) to the Sofia 2 SARS negative test results if the assay does Antigen, the first SARS-CoV-2 antigen test to receive such approval. not detect very low levels of viral Similar to nucleic acid–based tests widely used to diagnose SARS-CoV- nucleocapsid proteins 2 infection, antigen tests are used to detect active infections, and they may present advantages and disadvantages relative to nucleic acid– based diagnostics.
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Table 3.3. Recently Archived Topics: 7 Topics
Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Artificial intelligence (AI)– The American College of Cardiology recommends diagnostic cardiac ultrasonography (ie, Adding echocardiography to the workload of assisted echocardiography echocardiography) for patients with a COVID-19 diagnosis and symptoms of heart failure, bedside nurses could adversely impact their guidance for nonexpert enlarged heart, arrhythmia, or changes in electrocardiogram readings. The American Society delivery of care to other patients. Relying too users of Echocardiography has issued advice on protecting patients and ultrasound operators heavily on AI to compensate for frontline nurses’ when performing echocardiograms on patients with COVID-19, because some lack of specialized ultrasonography experience echocardiography techniques might risk spreading the virus if the patient coughs or gags could introduce unreasonable risk, especially in a during the examination. On May 12, 2020, FDA granted Caption Health expedited De Novo pandemic with high patient volumes. Such pathway clearance of an updated version of its Caption Guidance software, which limitations could limit widespread use, lessening purportedly allows nonexpert medical professionals to perform diagnostic-quality potential disruption. echocardiograms. The software uses AI to emulate expert sonographer guidance on image optimization and transducer placement and give automated feedback on image quality. According to Caption Health, the updated software features 88% more types of guidance than did the original version, improved algorithm performance, and optimized workflow. The developer stated FDA's expedited review was prompted by requests from clinicians at several US hospitals, detailing how the software could enable frontline providers to quickly assess cardiac function, reduce coronavirus exposure risk for health care personnel, and improve resource utilization in emergency departments and intensive care units.
Artificial intelligence (AI)– The need to quickly screen multiple patients for COVID-19 has prompted several groups to With the availability of rapid COVID-19 tests, assisted radiographic image develop AI methods to assess radiographic images for markers indicative of the viral radiographic assessments will likely remain assessment for COVID-19 infection in lung images. Much research focuses on chest x-ray or computed tomography secondary to laboratory testing for COVID-19 screening or diagnosis (CT), typically for screening or rapid diagnosis. Academic researchers and commercial screening and diagnosis. Further research of AI- developers of AI-assisted assessment of radiographic images to diagnose COVID-19 include assisted radiographic assessment is needed to DarwinAI (Waterloo, Ontario, Canada), University of Waterloo (Canada), ElectrifAi (Jersey study its potential for screening. Thus, this City, New Jersey), Cranfield University (United Kingdom), Simon Fraser University (Burnaby, assessment’s disruptive potential during the BC, Canada), and Thirona (Nijmegen, the Netherlands). However, some critics have advised pandemic will be quite low. the AI technology is still a work in progress and the software “training” currently relies too heavily on a relatively small data set of chest images collected from severely ill patients with advanced COVID-19 infection, potentially limiting effectiveness in identifying less severe cases. Both the American College of Radiology and the World Health Organization currently recommend against the routine use of chest x-rays or CT in COVID-19 screening or diagnosis.
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Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Artificial intelligence (AI)– Patients with existing cardiovascular disease have increased risk of complications and poor This technology appears to add additional steps assisted screening for low outcomes from COVID-19. Therefore, rapidly identifying cardiovascular disease in patients to cardiovascular assessment of patients with LVEF in suspected COVID-19 with confirmed or suspected COVID-19 could facilitate triage and disease management. On suspected or confirmed COVID-19 without infection May 13, 2020, FDA granted Eko Devices, Inc (Oakland, California), Emergency Use providing a clear additional diagnostic benefit to Authorization (EUA) for its Eko Electrocardiogram Low Ejection Fraction Tool (ELEFT) in assist physicians evaluating patients. The unclear adults as a diagnostic aid to screen for potential cardiac complications associated with benefit suggests low physician adoption, hence COVID-19 or underlying cardiac conditions that may affect clinical management of COVID- little disruptive potential. 19. ELEFT is a machine-learning algorithm that analyzes 10 seconds from a 12-lead electrocardiogram, typically using a hospital’s electronic medical record, to predict whether a patient has a low left ventricular ejection fraction (LVEF), defined as 40% or lower. Health care providers access the algorithm via a cloud-based software application program interface. ELEFT delivers a yes/no prediction to a provider's smartphone, tablet, or personal computing device. ELEFT is intended to help providers determine whether to order an echocardiogram for patients who otherwise might not receive one. ELEFT is not intended to replace an echocardiogram if otherwise indicated.
Pooled sample testing for Pooled sample testing is an approach that can be used to test for coronavirus infections in Pooled testing is an approach that increases the screening or diagnosis of populations with low disease prevalence and has the potential to reduce the number of tests testing capability of central laboratories without COVID-19 that need to be performed. Pooling involves combining samples from a group of individuals increasing costs and the use of testing supplies. and using a single test to rule out the presence of coronavirus. Only if a pool tests positive However, the accuracy of these tests has not are tests on the individual samples performed. A published study has shown that a single been demonstrated. A higher rate of false- positive sample can be detected by reverse transcriptase polymerase chain reaction (RT- negative results might cause individuals to PCR) in pools of up to 32 samples and possibly even 64 samples, provided additional PCR decrease their social distancing practices and amplification cycles are conducted. While this initial validation used quantitative RT-PCR to thus promote the spread of COVID-19. detect coronavirus nucleic acids, other detection methods, such as next-generation sequencing, might also be used. Pooled sample testing should not require additional equipment or substantial additional training and could reduce costs, decrease testing times, conserve reagents and materials, and expand testing to cover more individuals. FDA has granted Emergency Use Authorization (EUA) to the SARS-CoV-2 RNA RT-PCR test (Quest Diagnostics, Inc) and the COVID-19 RT-PCR test (Laboratory Corporation of America Holdings) to detect nucleic acid from SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in pooled samples containing up to 4 individual upper respiratory swab specimens.
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Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Protective booths for Shortages of personal protective equipment (PPE) have often complicated efforts to increase Use of protective booths would likely be COVID-19 testing the availability and volume of coronavirus testing during the pandemic. To help preserve reserved for permanent testing centers, limiting PPE, several centers have begun using protective booths to allow health care workers to disruption. The use of protective gloves could perform multiple coronavirus tests without changing PPE between patients. A provider in the limit health care workers’ dexterity for properly booth collects and stores patient samples outside the booth through surface-mounted collecting swab samples and adequately rubber gloves, avoiding the need for PPE. Providers may disinfect the booth's frequently disinfecting touch surfaces between patient touched external surfaces between patients, using the glove ports. An early version encounters. The cost of implementing booths protected providers on 3 sides with clear plastic walls. Later versions were fully enclosed and might outweigh any savings from preserving PPE featured positive-pressure high-efficiency particulate air (HEPA) filtration. Some commercial during patient testing. firms have subsequently developed larger booths resembling guard houses, with electrical connections and lighting, allowing the booths to be placed outside the entrances of hospitals or other facilities to test persons before building entry.
Robotic nasal swab The need to test many patients for coronavirus infection can increase exposure risk for Low likelihood of adoption will limit disruption. collection for COVID-19 frontline health care staff while depleting limited supplies of personal protective equipment Alternative test options than do not require testing (PPE). Brain Navi Biotechnology Co, Ltd (Zhubei City, Taiwan), has developed an autonomous nasopharyngeal swabs are becoming more Nasal Swab Robot for collecting patient samples on which to perform coronavirus testing. available. Wide use is unlikely based on the high The system purportedly uses facial recognition software to autonomously map a patient's cost of robotic technology generally and facial structure and collect swab samples from the uppermost nasopharyngeal target area resistance of patients to undergo uncomfortable with a robotic arm. During specimen collection, the patient is seated with the head placed sample collection from a robot. Thus far, against a stabilizing frame. A test operator oversees the autonomous procedure from the infection risk to health care workers collecting control console next to the seated patient, but behind a transparent plastic shield. After patient specimens has not been a widely cited sample collection, the robotic arm places the swab in a collection tube for transport and concern. laboratory analysis. The developer reports applying for FDA Emergency Use Authorization (EUA) to allow the robot’s use during the COVID-19 pandemic. Another company, Lifeline Robotics (Odense, Denmark), is reportedly developing a similar robotic system designed to autonomously collect throat swabs for coronavirus testing.
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Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Wastewater testing to The spread of COVID-19 infection, especially by asymptomatic individuals, coupled with It is unlikely that most municipal governments assess scale of COVID-19 limited clinical testing capacity, has spurred research into alternative testing methods to would direct limited resources to wastewater outbreak detect the scope and dispersal patterns of COVID-19 infection. Several researchers have testing, especially as the pandemic has strained proposed testing wastewater from sewage systems for an early warning, especially using public health capacity. In areas without known localized testing of high-risk communities such as nursing homes. Wastewater testing might outbreaks, the usefulness of wastewater testing indicate COVID-19 community infection before cases are identified at health care facilities would require public health guidance to help the via diagnostic testing. Further, increased viral particle levels of SARS-CoV-2 (severe acute public protect itself. In areas with recognized respiratory syndrome coronavirus 2; the virus that causes COVID-19) detected in wastewater outbreaks, wastewater testing would be of could predict increasing numbers of infected individuals requiring treatment. New research limited use. suggests fecal viral load may rebound and persist after nasal swab testing registers negative results. Applying nucleic acid−based polymerase chain reaction (PCR) assays to wastewater testing has high specificity and sensitivity, but this approach can be costly and requires more time and specialized personnel to perform the tests. Simpler and cheaper DNA detection methods, such as paper-based microfluidic indicators, enzyme-linked immunosorbent assay (ELISA), or biosensors, might allow for high-quality precision diagnosis of COVID-19 in localized regions. Biobot Analytics, Inc (Somerville, Massachusetts), is one US-based firm offering sewage testing to local governments.
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Section 4. Systems and Management: 13 Topics
Table 4.1. Topics Added Since Last Status Report: 5 Topics
Title Description Possible areas of impact Possible future impacts
3D-printed face shields to The rapid influx of patients with COVID-19 infection substantially Clinician and/or caregiver Might alleviate face shield shortages protect against COVID-19 depleted many health care facilities' supplies of personal protective safety for frontline health care personnel infection equipment (PPE) for staff. Competition among hospitals for limited Might reduce supply costs if face vendor supplies of PPE has resulted in dramatically rising prices, shields can be 3D printed locally prompting some academic medical centers to redirect their in-house 3- dimensional (3D) printing capabilities to address PPE shortages. At several centers, including the University of Washington and Mississippi State University, engineers and health care personnel have collaborated to rapidly shift their 3D printing capacity to produce protective face shields for frontline staff. In some cases, collaborative teams have produced face shields that a facility's personnel prefer to commercially available shields, using modifications based on personal needs and feedback from local staff.
Artificial intelligence (AI)– Identification and monitoring of patients with COVID-19 who are at risk Patient outcomes Might assist health care professionals assisted radiographic image of developing severe disease is of great importance and may help Population health to make better treatment decisions assessment for determining health care facilities prioritize care and efficiently allocate resources. AI Might help manage the surge of COVID-19 prognosis algorithms are being investigated for use in assisting with radiographic Clinician and/or caregiver safety patients requiring ventilators and image (eg, chest x-ray, computed tomography) analysis to predict the alleviate the burden on health care clinical course of COVID-19. Examples of AI-assisted image assessment Health care delivery and professionals and facilities in development include an AI-driven computational tool to decide process Might help inform future triage which patients need the most extensive treatment (eg, mechanical Health care costs ventilation), a machine learning–based model for predicting length of paradigms hospital stay, and an AI-driven model for predicting malignant Might lead to inappropriate care in progression of COVID-19 pneumonia. cases of misclassification by the algorithm
SECTION 4. SYSTEMS AND MANAGEMENT 40
Title Description Possible areas of impact Possible future impacts
Multidose vials to Drug developers are quickly advancing coronavirus vaccine candidates Population health Might improve understanding of strengthen vial supply chain through clinical trials and, in parallel, readying manufacturing to Health care delivery and supply chain management and help during COVID-19 prepare for deployment if their candidate proves to be safe and process prepare for future public health effective. A recent news brief highlighted a shortage of the medical- emergencies Health care disparities grade glass vials needed to distribute vaccines. A shortage of these Might change standards for quality glass vials or syringes could create access issues for millions of people. and manufacturing throughput of Currently, to conserve glass supply, the industry has decided to use 10- pharmaceutical packaging milliliter vials that are capable of holding 8 to 15 doses of coronavirus vaccine. Corning, Inc, will receive funding from the Biomedical Might increase access to COVID-19 Advanced Research and Development Authority (BARDA) to accelerate vaccines, potentially accelerating the manufacturing of glass vials for COVID-19 vaccines and treatments. herd immunity to control the spread of COVID-19 Might increase risks of iatrogenic illness due to cross-contamination
Neutralizing masks to limit The transmission of coronavirus might be limited by face masks Patient outcomes Might enhance the protective effects the spread of COVID-19 thought to block respiratory droplets released from coughing, Population health of current personal protective sneezing, or talking. Multiple companies are investigating novel equipment (PPE), such as masks, materials with viral-neutralizing properties with which to construct face Clinician and/or caregiver against respiratory viruses safety masks. Vomaris Innovations, Inc, has developed a material with Might increase safety of health care moisture-activated microcell batteries that is currently in use as a Health care costs professionals in hospitals and clinics broad-spectrum antimicrobial dressing. A recent study of this material demonstrated that the low-level electric field–generating fabric could Might expand the application of reduce the infectivity of coronavirus when the virus was in contact with bioelectric technology in health care the fabric for 1 to 5 minutes. Another material, Acteev Biodefend, uses Might improve mask reusability by active zinc ions embedded in polyamide-based nonwoven and inactivating viruses on mask surfaces nanofiber materials and has been shown to be 99% effective against various microbes and viruses (including coronavirus). On July 30, 2020, Ascend Performance Materials submitted its first FDA 510(k) to market surgical masks made using Acteev technology.
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Title Description Possible areas of impact Possible future impacts
Pandemic response In August 2020, the Centers for Disease Control and Prevention (CDC) Patient outcomes Might improve mental health strategies to mitigate urged a public health response to increase intervention and prevention Population health outcomes not only for those affected mental health effects of the efforts for mental health conditions in the wake of COVID-19. Pandemic directly by COVID-19 but also for COVID-19 pandemic response strategies specifically designed to address mental health Health care delivery and those affected indirectly process issues might lessen the many negative mental health effects associated Might improve interdisciplinary with the current COVID-19 pandemic. These structured frameworks are Health care disparities collaboration and institutional intended to mobilize and optimize health care delivery to meet public Health care costs cohesion health needs during a pandemic. A recently proposed behavioral health pandemic response strategy proposed actionable steps related to 6 Might revolutionize the mental health pandemic phases, to address mental health demands during the care delivery system if implemented COVID-19 pandemic. Examples of action steps include identifying and processes are adapted sustainably training crisis leadership teams, designing psychologically informed Might decrease the stigma of mental prevention and education campaigns and programs, training future health disorders behavioral health specialists for public health crisis response, Might increase health disparities for developing flexible and scalable behavioral health services, advancing individuals living in rural areas, who behavioral health research, and ameliorating health disparities and cannot readily access mental health discrimination through outreach and raising awareness. Caring resources, or decrease health Communities is one such initiative to implement a behavioral health disparities through efforts aimed response strategy during the COVID-19 pandemic, using a team of specifically to do so more than 100 psychologists, psychiatrists, transdisciplinary physicians, social workers, interdisciplinary trainees, and staff with expertise in web design and operations. A disaster psychiatry team mobilized by Massachusetts General Hospital in April 2020 follows a psychological first aid framework and aims to help the especially vulnerable homeless population.
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Table 4.2. Currently Monitored Topics: 5 Topics
Title Description Possible areas of impact Possible future impacts
Contact tracing software Software developers across the world are collaborating to combat Patient outcomes Might help governments and health systems to mitigate COVID-19 by creating contact tracing tools that can inform Population health agencies develop policies to reduce epidemic scenarios governments and public health agencies about the spread of the spread of COVID-19 coronavirus. Apple and Google have launched exposure notification Health care delivery and process Might increase privacy concerns, systems using Bluetooth-enabled devices such as smartphones to track especially for COVID-19-positive physical proximity between people. Users of the system can opt to Health care disparities users report a COVID-19 diagnosis, allowing efficient contact tracing by alerting users whose devices have been in close proximity to users who Might lead to poor population health have received a positive COVID-19 diagnosis. Additionally, access to outcomes due to targeted advertising the data will be granted to public health systems, which may allow and mistaken self-diagnoses them to provide advice on next steps to potentially exposed users. Another developer in this space is EnGenius Technologies (Costa Mesa, California), a wireless networking company that has developed a new feature on its cloud platform to identify—using Wi-Fi—surrounding user devices. The state governments of North Dakota, South Dakota, and Utah are already using mobile applications for contact tracing, namely Care19 and Healthy Together, that rely on a combination of Bluetooth and Global Positioning System (GPS) data to track person-to- person transmissions as well as transmission zones in their states.
SECTION 4. SYSTEMS AND MANAGEMENT 43
Title Description Possible areas of impact Possible future impacts
Drive-through prenatal care The COVID-19 pandemic has shifted a substantial amount of health Patient outcomes Might reduce potential exposure to model to reduce COVID-19 care to the telehealth setting. However, some assessments that are Population health COVID-19 infection for both the exposure part of routine prenatal care still require direct interaction between patient and health care staff patients and health care providers. To provide access to prenatal care Clinician and/or caregiver safety Might reduce patient anxiety by while limiting COVID-19 exposure risk for obstetric providers and allowing continuation of planned patients, investigators at Baylor College of Medicine (Houston, Texas) Health care delivery and prenatal visits that cannot be developed a drive-through prenatal care model in which pregnant process completed via telehealth women would remain in their cars while being assessed by health Health care disparities care providers. Services such as blood pressure measurement, fetal Might reduce costs for the patient by heart rate assessment, and select ultrasound assessments are Health care costs reducing health care utilization provided during drive-through appointments. Additionally, the Might offer convenient, timely developers claim that the availability of these professional prenatal care for patients who have interactions might reduce patient anxiety related to having fewer inadequate internet access or limited prenatal clinic visits and could ease pandemic-related fears related to computer literacy for telehealth visits potential exposure within the clinic. The program uses equipment and Might lead to long wait times if the disposables common to obstetric clinics in the United States. The drive-through test center is investigators estimate that a drive-through prenatal care model overwhelmed might reduce the number of in-person clinic visits by 33% per patient compared with standard prenatal care modalities.
Machine learning to predict COVID-19 has had significant social, political, economic, and public Patient outcomes Might help predict changes in the spread of COVID-19 health impacts globally. The Centers for Disease Control and Prevention Population health national and state-level spread of (CDC) has partnered with several universities to forecast national and coronavirus, the virus that causes state-level changes in infection rates and deaths due to COVID-19. Clinician and/or caregiver COVID-19 safety Typically, projections for the spread of infectious diseases are Might inform public health agencies performed by curve-fitting, using reported cases. Machine-learning Health care delivery and to establish appropriate reopening models are now being used to predict the spread of this rapidly process procedures evolving virus. One such prediction model that feeds into the CDC’s Health care disparities online forecast is the UCLA-SuEIR, developed at the University of Might reduce overall health care California, Los Angeles, by the UCLA Statistical Machine Learning Health care costs costs by predicting earlier than other Laboratory. This machine-learning model purportedly infers the spread models possible resurgence in cases, of infection while accounting for underlying epidemic dynamics, thereby helping with emergency making it a more comprehensive prediction model. preparedness
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Title Description Possible areas of impact Possible future impacts
Rapid expansion of Response to the COVID-19 pandemic (ie, stay-at-home orders, strict Patient outcomes Might facilitate remote or home telemedicine driven by social distancing guidelines) has prompted health care providers across Clinician and/or caregiver monitoring of suspected COVID-19 widespread COVID-19 all clinical specialties to rapidly adopt methods of care for non-COVID- safety cases without increasing burden on response 19 patients. Whether for patients with acute or chronic conditions, the health care facilities new methods are meant to maintain the safety of patients and clinical Health care delivery and process Might reduce disruptions in care staff. Telemedicine technologies offer providers and patients multiple continuity for individual patients with ways to connect with virtual visits that attempt to compensate for the Health care disparities acute or chronic conditions unrelated lack of in-person physician-patient contact and to help maintain care to COVID-19 plans. The pandemic has prompted regulators and insurers to loosen regulations and reimbursement restrictions that traditionally limited Might present technical and telemedicine to rural areas with limited access to providers. Thus, operational challenges to provider adoption has increased broadly. Some experienced centers have practices without telemedicine offered guidance for quickly implementing a telemedicine system in experience clinical practice. Other experts have noted that the broad expansion of Might lead to long-term changes in health care information technology (IT) use prompted by COVID-19 how care is delivered after the provides an opportunity to improve public health surveillance during pandemic subsides, based on patient infectious disease outbreaks that would be optimized by an as-yet and provider experiences unrealized robust national health IT infrastructure. The long-term impact of these changes remains unclear. In August 2020, electronic medical records firm Epic Systems Corporation reported that telemedicine use peaked in April 2020 (about 70% of US health care visits vs 30% office visits) and declined to about 21% of US health care visits versus 79% office visits by July 2020.
SECTION 4. SYSTEMS AND MANAGEMENT 45
Title Description Possible areas of impact Possible future impacts
Statewide patient load The Arizona Department of Health Services (ADHS) has launched a Patient outcomes Might optimize interfacility transfer management during the statewide patient load balancing system (ie, surge line) to help with Population health of patients during the COVID-19 COVID-19 pandemic transferring patients between facilities during the COVID-19 public pandemic or similar emergency health emergency. ADHS hopes that the system will help Clinician and/or caregiver situations safety accommodate potential surges in the number of COVID-19 cases, Might assist health care staff with which have led some hospitals to cancel or postpone elective Health care delivery and effective time management by procedures. The Arizona Surge Line is a 24/7 toll-free call line for process reducing their call time to find the health care providers. For each call, a surge line transfer agent Health care disparities right level of care for their patients reviews critical care availability for each hospital in the state and transfers the call to the appropriate destination, thereby assisting Health care costs Might improve patient survival with interfacility transfer of patients with presumed or confirmed outcomes by providing appropriate COVID-19 or transfer of patients to post-acute care facilities. It can care in a timely manner assist with effectively distributing new staffing placements from out Might enhance government policies of state. The surge line may also provide clinical consultation if a and public health emergency transfer is declined or delayed. The Oregon Health Authority has also guidance developed a statewide hospital capacity system using a real-time data-tracking tool to efficiently manage the surge in COVID-19 patients. These efforts might encourage other states to create similar statewide hubs with real-time visibility into bed capacity and the availability of ventilators across all facilities and health care systems.
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Table 4.3. Recently Archived Topics: 3 Topics
Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
COVID-19-specific Creating COVID-19-specific psychiatric units might keep psychiatric inpatients safer by COVID-19-specific psychiatric units are likely to psychiatric units separating those who test positive for SARS-CoV-2 (severe acute respiratory syndrome be costly and resource intensive to implement coronavirus 2) from those who test negative. Patients hospitalized with psychiatric and maintain. As a result, many hospitals and conditions often receive care in group settings (eg, talk therapy, art therapy), which puts facilities might be unable to support them. them at a higher risk for infection during the COVID-19 pandemic. Additionally, some may Efforts to sort psychiatric patients by SARS-CoV- have psychiatric conditions that make it especially hard to adhere to 6-foot social distancing 2 test results might be complicated by long wait recommendations and wearing masks. Therefore, placing psychiatric inpatients who test times for results and inaccurate results. positive for SARS-CoV-2 in a COVID-19-specific psychiatric unit at admission might help keep those who test negative safer while they undergo inpatient psychiatric treatment and allow them to continue to attend group therapy classes and interact socially. Psychiatric patients placed in the COVID-19 psychiatric unit will be able to receive group therapy; however, at other times they are encouraged to stay in their rooms and eat meals there.
Thermal cameras for wide- Security firms are marketing thermal cameras and related thermal-imaging software to Likely low implementation of this technology area temperature scanning businesses to scan customers or employees entering a store or workplace for suspected limits its disruptive effect. Temperature screening in public spaces coronavirus infection. These thermal camera systems purportedly detect elevated skin is largely ineffective for containing the spread of temperatures in people passing the cameras and alert designated personnel, via text, email, infectious disease. Accuracy of these systems or computer video alert, allowing them to further screen targeted individuals with additional varies widely, owing to changes in ambient in-person temperature screening. Some systems employ artificial intelligence (AI)–assisted conditions. Addition of facial recognition to facial recognition technology in addition to thermal imaging. body temperature is likely to raise privacy concerns, especially in the current political climate.
Vending machines to Personal protective equipment (PPE) such as masks, gloves, and gowns has been the Distribution of masks and other forms of PPE is increase access to personal subject of heightened attention during the COVID-19 pandemic. Cleanlife, an FDA- no longer a disruptive concern at this point in protective equipment registered distributor of PPE and medical safety products, and D & S Vending, a supplier the pandemic. Those who comply with use of of equipment and parts to the vending industry, are teaming up to distribute PPE PPE are already doing so, since masks are widely supplies through vending machines, according to a press release. Initially, 6 different available at many commercial stores, resulting in PPE kits will be available for vending operators to purchase and sell through their snack only a small impact on population health. machines. These kits are designed to work with existing dispensing coils in the machines. Another example of PPE distribution via vending machines includes Sani- Center PPE Vending Machines that carry 25 to 34 disinfecting and PPE items and accept cashless payment options to prevent transmission risk among consumers.
SECTION 4. SYSTEMS AND MANAGEMENT 47
Section 5. Treatments: 34 Topics
Table 5.1. Topics Added Since Last Status Report: 16 Topics
Title Description Possible areas of impact Possible future impacts
ANG-3777 to treat patients Some patients with COVID-19 experience severe respiratory distress Patient outcomes Might improve health outcomes and hospitalized with COVID-19 and multiple organ failure due to the direct effects of viral infection and quality of life by preventing or pneumonia indirect effects associated with the body's response to the virus. ANG- reducing the risk of acute lung and 3777 is an investigational hepatocyte growth factor (HGF) mimetic that kidney injury due to COVID-19 might mitigate or prevent acute lung or kidney injury caused by pneumonia COVID-19. HGF is purportedly essential for activating the c-Met Might lessen burden on the health cascade in response to acute organ injury, which promotes tissue and care system by reducing demand on organ repair. ANG-3777 was developed to have a longer half-life (3 mechanical ventilators and dialysis hours) than HGF (less than 5 minutes) and is administered as a daily devices as well as hospitalization intravenous infusion for 4 days in clinical trials. A phase 2 randomized length of stay trial is comparing ANG-3777 with placebo in patients (n = 100) hospitalized in Brazil with severe COVID-19 pneumonia and receiving standard of care treatment. The primary end point of this trial is the proportion of patients free of the requirement for mechanical ventilation or renal replacement therapy, and primary completion is anticipated in October 2020. If successful, the company plans to conduct clinical trials in the United States.
SECTION 5. TREATMENTS 48
Title Description Possible areas of impact Possible future impacts
Auxora to treat severe Auxora (CalciMedica Inc, San Diego, California) is an investigational, Patient outcomes Might improve patient health COVID-19-associated intravenously administered inhibitor of the calcium release–activated Population health outcomes by shortening recovery pneumonia calcium (CRAC) channel that is in clinical development to treat severe time and minimizing need for COVID-19-related pneumonia. Auxora might protect the cells lining the Health care disparities invasive mechanical ventilation lungs against damage, increase oxygen saturation, and prevent the Might improve population health release of cytokines (proinflammatory proteins) thought to contribute outcomes by decreasing the burden to hyperinflammation and respiratory disease severity in COVID-19. on the health care system Data published August 14, 2020, from an open-label, randomized portion of an ongoing, developer-sponsored, phase 2 trial showed that Might improve understanding of patients given Auxora in addition to standard of care treatment (17 mitigating hyperinflammation to with severe and 3 with critical COVID-19) resulted in a median time to treat COVID-19 recovery of 5 days and a mechanical ventilation rate of 18% compared Might increase health disparities if with patients receiving standard of care treatment alone (9 with severe Auxora is available in only limited and 1 with critical COVID-19), who had a median time to recovery of 12 quantities upon authorization or days and a mechanical ventilation rate of 50%. The developer- approval for clinical use sponsored phase 2 trial will be expanded to a 400-patient, double- blind, randomized controlled trial with a primary completion date in March 2021.
CYT107 for treating CYT07 (Revimmune, Inc, Bethesda, Maryland) is a recombinant Patient outcomes Might reduce health complications hospitalized patients with therapeutic form of interleukin-7 (IL-7), a key cytokine involved in Health care costs related to immunosuppression COVID-19-related human T-cell survival and expansion. The factor purportedly can induce Might reduce health care costs lymphopenia the proliferation of naïve T cells to help replenish immune cells lost related to length of hospitalization during the course of COVID-19-related cytokine storms and sepsis. T- and use of intensive care resources cell counts are dramatically reduced during COVID-19 infection, which studies have shown has a negative correlation with patient survival. Results from a phase 2 clinical trial that studied IL-7’s ability to restore lymphocyte counts in sepsis patients showed that CYT107 reversed lymphopenia (low levels of lymphocytes) and improved immunity in patients with life-threatening sepsis. An ongoing phase 2 randomized trial in the United Kingdom is studying the ability of CYT107 to improve clinical outcomes in lymphopenic patients with COVID-19, with a primary completion date of October 30, 2020. Participants (n = 48) with COVID-19 and absolute lymphocyte counts under 1000 cells/mm3 will be randomly assigned to twice weekly intramuscular injections of CYT107 (10 mg/kg) or placebo for 2 weeks and will be checked for immune reconstitution and clinical improvement.
SECTION 5. TREATMENTS 49
Title Description Possible areas of impact Possible future impacts
Dapagliflozin to reduce risk Dapagliflozin (Farxiga) is a sodium glucose cotransporter 2 (SGLT2) Patient outcomes Might reduce the risk of organ of complications from mild inhibitor that lowers blood glucose by promoting the excretion of Population health damage, preventing disease to moderate glucose into the urine. It is an oral drug approved by FDA to treat type progression and increasing survival Health care costs COVID-19 2 diabetes mellitus (diabetes) and heart failure and has been shown to Might reduce burden on the health improve outcomes in patients with type 2 diabetes, heart failure with care system reduced ejection fraction, and chronic kidney disease. Worse outcomes from COVID-19 have been seen in patients who have preexisting heart, Might decrease health care costs kidney, and metabolic diseases, as well as in patients with elevated associated with longer blood glucose levels without a previous diagnosis of diabetes. hospitalizations, intensive care Dapagliflozin is being investigated as a potential treatment to reduce resources, and treating health the risk of serious complications and organ failure in patients with mild complications of COVID-19 to moderate COVID-19 who have cardiovascular, metabolic, or kidney Might improve understanding of the disease risk factors. A retrospective study of diabetic patients with role of preventing organ damage in COVID-19 found that well-controlled blood glucose correlated with COVID-19 and outcomes for patients improved outcomes. AstraZeneca is sponsoring a phase 3 trial in the with heart, kidney, and metabolic United States that has a primary completion date in October 2020. The disease risk factors trial is enrolling 900 hospitalized participants with mild to moderate COVID-19 who have at least one of the following: hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, or stage 3 or 4 chronic kidney disease.
SECTION 5. TREATMENTS 50
Title Description Possible areas of impact Possible future impacts
EDP1815 for treating EDP1815 is an investigational, orally administered probiotic consisting Patient outcomes Might reduce the number of patients Prevotella histicola hospitalized patients with of the bacterium . It is under development by Evelo Health care costs progressing to severe stages of COVID-19 symptoms and Biosciences for treating COVID-19 symptoms and complications. COVID-19 complications EDP1815 purportedly engages the immune system in the small Might reduce the number of patients intestine to modulate systemic immune responses, an interface the requiring oxygen therapy and/or developer refers to as the small intestinal axis (SINTAX). Immune cells mechanical ventilation from around the body circulate through lymphoid tissues of the small intestine and become conditioned by exposure to antigens, Might reduce length of hospital stay immunomodulatory agents, and microbes in the gut. EDP1815 is a Might cause adverse events related strain of a naturally evolved human gut commensal microbe that to amplification of immune signaling reprograms immune cells in the small intestine, which go on to cascade modulate effector cells in lymph nodes. The effector cells purportedly circulate through the lymphatic system to exert systemic therapeutic effects. Early data from a phase 1b trial in psoriasis suggests that EDP1815 might modulate multiple immune pathways associated with cytokine storms in COVID-19 patients, without the risks associated with immunosuppression. A phase 2 double-blind trial is investigating daily dosing of EDP1815 versus placebo for 14 days in 60 patients hospitalized with COVID-19, with primary completion in December 2020.
Garadacimab (CSL312) for Garadacimab (CSL312), is an investigational monoclonal antibody that Patient outcomes Might reduce the instances of treating respiratory distress functions as a factor XIIa (FXIIa) antagonist and might reduce the tracheal intubation and death caused by incidence of tracheal intubation or death in patients with COVID-19- Might reduce burden on the health COVID-19 related respiratory distress. Patients with severe COVID-19 have severe care system by reducing intubation inflammatory cascades that can trigger intravascular coagulation and and length of stay thrombus formation, leading to multiple organ failure. Garadacimab blocks the action of FXIIa, a serum protein involved in the blood Might improve understanding of clotting cascade. Garadacimab is being evaluated in a phase 2 anticoagulants for treating COVID-19 randomized controlled trial compared with placebo for treating 124 Might cause adverse events related adults with COVID-19-related pneumonia, with primary completion in to reduced blood clotting December 2020.
SECTION 5. TREATMENTS 51
Title Description Possible areas of impact Possible future impacts
Hyperimmune Coronavirus-specific hyperimmune immunoglobulin (H-IG) is a Patient outcomes Might improve patient health immunoglobulin for preparation of purified human immunoglobulins formulated from Population health outcomes and increase survival treatment of COVID-19 pooled plasma collected from a large number of patients who have Might reduce the burden on the recovered from SARS-CoV-2 (severe acute respiratory syndrome Health care delivery and process health care system and the risk of coronavirus 2) infection. Neutralizing antibodies against coronavirus mechanical ventilator shortages present in H-IG might confer passive immunity to the virus and, Health care disparities Might increase the cost of treating therefore, could be used as a potential treatment for patients with Health care costs COVID-19. H-IG has several potential benefits compared with use of COVID-19, which could be partially convalescent plasma (CP) from single donors, including the ability to offset by reductions in costs standardize the dose, improved shelf life, and higher antibody associated with hospitalization and concentrations. Higher antibody concentrations allow for lower intensive care resources transfusion volumes, which might protect against certain infusion reactions (eg, transfusion-associated circulatory overload). Multiple efforts to produce an H-IG product are under way, including development programs by the COVIg-19 Plasma Alliance, Emergent BioSolutions (Rockville, Maryland), and Grifols SA (Barcelona, Spain). In collaboration with one or more of these developers, the National Institute of Allergy and Infectious Diseases is intending to sponsor multiple trials of H-IG as a treatment for patients with COVID-19.
SECTION 5. TREATMENTS 52
Title Description Possible areas of impact Possible future impacts
Intermediate- or Coagulopathy is a common complication of COVID-19 and might Patient outcomes Might improve patient health therapeutic-dose heparin lead to increased rates of venous thromboembolic events, such as Population health outcomes and increase survival anticoagulation for patients deep vein thrombosis and pulmonary embolism, in affected patients. Health care costs Might reduce the burden on the hospitalized for COVID-19 Additionally, extensive microvascular thrombosis in the lungs has health care system and lower been observed in autopsies of COVID-19 patients, suggesting mechanical ventilator shortages coagulopathy might play a role in disease pathogenesis. Guidelines from both the American Society of Hematology and the American Might decrease health care costs College of Chest Physicians recommend that all patients hospitalized associated with hospitalization and with COVID-19 receive anticoagulant thromboprophylaxis with low- intensive care resources molecular-weight heparin (LMWH) at the standard prophylactic dose. Might improve understanding of the However, retrospective studies have observed the persistence of role of anticoagulation in the thromboembolic events in patients despite receiving the standard treatment of COVID-19 prophylactic heparin dosing, prompting researchers to investigate if Might increase the risk of treatment- patients hospitalized with COVID-19 should receive higher doses of induced bleeding events heparin. In particular, a large international trial (n = 3000) with primary completion in January 2021 and a large Italian trial (n = 2712) with primary completion in August 2020 are investigating the safety and efficacy of increased heparin dosing (eg, intermediate dosing, therapeutic dosing, weight-based dosing) compared with standard prophylactic heparin dosing in patients hospitalized with COVID-19. Multiple smaller, US-based trials of heparin dosing are also registered at the National Library of Medicine’s clinical trials registry.
SECTION 5. TREATMENTS 53
Title Description Possible areas of impact Possible future impacts
Intravenous immune Excessive release of proinflammatory proteins in response to SARS- Patient outcomes Might reduce the need for globulin (human) to treat CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is Health care costs supplemental oxygen or mechanical severe COVID-19 thought to contribute to COVID-19 severity and poor clinical outcomes. ventilation Intravenous immunoglobulin (IVIG) is a human plasma product Might increase direct cost of consisting of normal human immune globulins (antibodies) derived treatment while potentially reducing from a pool of several thousand healthy donors that is FDA approved downstream health care costs and for, and used off-label to treat, a variety of immune deficiency and burden on the system if length of autoimmune disorders. IVIG might reduce hyperinflammation and risk hospitalization is reduced of cytokine storm in patients hospitalized with severe COVID-19, by increasing levels of autoreactive antibodies that bind cytokines and by Might cause IVIG shortages for blocking innate immune effector cell activation. A prospective study patients who require the biologic for evaluating IVIG found that it significantly improved hypoxia and other diseases reduced hospital length of stay as well as the rate of progression of respiratory failure requiring mechanical ventilation in COVID-19 patients. Ongoing US clinical trials investigating the use of IVIG to treat COVID-19 include phase 4 (n = 40), phase 3 (n = 208), and phase 2 (n = 100) trials, all with primary completion dates in 2020. Based on a treatment regimen consisting of a total dose of 2 g/kg body weight and an average patient weight of 88.8 kg, 2 representative IVIG options, Gamunex-C and Octagam, cost between about $22 000 and $32 000.
Machine learning to identify The widening scope of the coronavirus pandemic has prompted several Population health Might expedite search for approved drug candidates to treat researchers to evaluate whether artificial intelligence (AI) can identify Health care costs drugs that could benefit patients with COVID-19 therapeutic agents that might offer potential benefit in treating COVID- COVID-19 if used off-label 19. Gates and Hamed (Norwich University, Northfield, Vermont) Might expedite search for drug developed the CovidX Network Algorithm to identify drugs approved candidates that could benefit for other indications that might help treat COVID-19 (ie, repurposing patients with COVID-19 drugs for off-label use). Kowalewski and Ray (University of California, Riverside) used machine-learning techniques to predict drugs' Might provide a useful model for effectiveness against COVID-19 from an analysis of 100 000 FDA- rapid discovery of potential drugs approved drugs and registered chemicals and about 14 million other targeting emerging pathogens in commercially available chemicals. They propose that findings could future pandemics identify FDA-approved drugs suitable for repurposing or short-term approval and other agents requiring longer-term study. Piplani et al identified 84 potential COVID-19 therapeutics among antiviral agents, including simeprevir, sofosbuvir, lopinavir, ritonavir, and remdesivir, and other drugs developed for other indications.
SECTION 5. TREATMENTS 54
Title Description Possible areas of impact Possible future impacts
Nitazoxanide (NT-300) to Nitazoxanide, an oral drug with broad-spectrum antiviral properties, is Patient outcomes Might reduce recovery time and risk treat mild to moderate being developed as the extended-release formulation NT-300 (Romark Population health of progression to severe COVID-19 COVID-19 Laboratories LC) to treat mild to moderate COVID-19. In cell cultures in Health care costs Might decrease the burden on the the lab, nitazoxanide has been found to inhibit the replication of health care system multiple coronaviruses, including SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), SARS-CoV (severe acute respiratory Might improve understanding of syndrome–associated coronavirus), and MERS-CoV (Middle East mitigating hyperinflammation to respiratory syndrome coronavirus), as well as other viruses, such as treat COVID-19 those that cause the flu and the common cold. In addition to inhibiting Might result in cost savings if the replication of viruses, nitazoxanide purportedly suppresses the drug cost is outweighed by potential production of various proinflammatory proteins called cytokines. This health care costs saved with better action might treat mild to moderate COVID-19 by moderating an outcomes, or result in higher costs if overexaggerated inflammatory response to SARS-CoV-2 (ie, the drug is more expensive than hyperinflammation), which is thought to contribute to severe disease potential health care costs saved and poor outcomes. NT-300 is being investigated in a developer- sponsored phase 3 trial (n = 800) that has a primary completion date in October 2020. Participants are given oral NT-300 twice daily for 5 days.
SECTION 5. TREATMENTS 55
Title Description Possible areas of impact Possible future impacts
Opaganib to treat Opaganib (Yeliva, RedHill Biopharma, Tel-Aviv, Israel), is a selective Patient outcomes Might lower risk of progression to pneumonia associated with inhibitor of the enzyme sphingosine kinase-2 (SK2). It is in development Population health more severe disease, reduce lung COVID-19 to treat various cancers. Opaganib has demonstrated antiviral activity scarring, and increase survival against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Clinician and/or caregiver safety Might reduce the burden on the and antiinflammatory properties in preclinical models, and might health care system by shortening improve outcomes in patients with pneumonia associated with COVID- Health care costs hospitalization time per patient and 19. Specifically, its inhibition of sphingolipid metabolism might reducing the need for mechanical attenuate proinflammatory processes that are thought to contribute to ventilation severe disease course and worsened prognosis in COVID-19. Additionally, SK2 purportedly plays a role in the replication of single- Might improve understanding of stranded RNA viruses such as SARS-CoV-2, and, therefore, opaganib hyperinflammation in COVID-19 and may have antiviral activity. Opaganib is being administered orally in potential treatments addition to standard of care therapy to hospitalized patients with Might only minimally affect disease COVID-19-associated pneumonia requiring supplemental oxygen, in a severity, and its use in patients might phase 2 proof-of-concept study (n = 40) and a phase 2/3 study detract from treatment with more (n = 270). The primary completion dates for these trials are in October efficacious investigational therapies 2020 and January 2021, respectively. Data published June 23, 2020, on compassionate use of opaganib in 7 patients with severe COVID-19 suggested opaganib was well tolerated and improved clinical and laboratory parameters. In August 2020, the developer announced plans to potentially submit applications for several Emergency Use Authorizations (EUAs) as early as the end of 2020.
SECTION 5. TREATMENTS 56
Title Description Possible areas of impact Possible future impacts
Pamrevlumab for treating Pamrevlumab is an investigational monoclonal antibody that inhibits Patient outcomes Might reduce the number of patients hospitalized patients with the activity of connective tissue growth factor (CTGF). CTGF is Health care costs requiring mechanical ventilation acute COVID-19 associated with fibrotic and proliferative diseases that cause and/or extracorporeal membrane persistent and excessive scarring, which can lead to organ oxygenation (ECMO) dysfunction and failure. The factor might promote vascular leakage Might reduce the need for and lead to pulmonary edema related to acute COVID-19-related supplemental oxygen in patients with pulmonary disease. These processes may cause a reduction in COVID-19-induced pneumonia oxygenation, which can lead to severe respiratory failure. Pamrevlumab might mitigate or reverse the edema caused by CTGF, Might reduce hospital length of stay by inhibiting the growth factor, protecting the lungs from COVID-19- Might cause adverse events related induced pneumonia, and improving oxygenation. A phase 2 to inhibiting CTGF function, including randomized trial is ongoing, comparing weekly intravenous infusions cell adhesion, migration, proliferation, of pamrevlumab with placebo in patients (n = 130) aged 40 to 85 angiogenesis, skeletal development, years hospitalized with acute COVID-19, with primary completion in or tissue wound repair December 2020.
Recombinant plasma Recombinant plasma gelsolin (Rhu-pGSN) is an investigational Patient outcomes Might reduce the incidence or gelsolin (Rhu-pGSN) for antiinflammatory treatment under study for treating severe COVID-19 Population health severity of COVID-19 organ damage, treating COVID-19 pneumonia. Gelsolin is a naturally occurring protein that acts through potentially reducing the need for pneumonia multiple mechanisms to modulate host inflammatory reactions and Health care costs mechanical ventilation or dialysis enhance immune clearance of microbes and toxins. Gelsolin is Might lessen the burden on the abundant in healthy individuals, but severe injury and infection health care system by reducing the deplete it, which may contribute to excessive inflammatory responses, length of stay in the intensive care organ damage, and death. Gelsolin depletion has been associated unit and hospitalization with poor outcomes in COVID-19, and supplementing depleted levels of gelsolin with Rhu-pGSN might help mitigate the debilitating Might reduce long-term effects from effects of cytokine storm and severe inflammation seen in COVID-19 severe COVID-19 organ damage patients. A phase 2 randomized controlled trial is evaluating Rhu- pGSN compared with placebo in 60 adults with COVID-19 pneumonia, with primary completion in October 2020. Patients will be given 3 doses of Rhu-pGSN, along with standard of care treatment, to evaluate its efficacy (survival without organ failure on day 14), safety, and tolerability.
SECTION 5. TREATMENTS 57
Title Description Possible areas of impact Possible future impacts
Sargramostim (Leukine) for Sargramostim (Leukine) is a recombinant form of human granulocyte- Patient outcomes Might reduce mechanical ventilation treating patients with macrophage colony-stimulating factor (GM-CSF), approved by FDA for Health care costs time and increase survival in patients COVID-19-associated various applications requiring the proliferation or reconstitution of with ARDS respiratory illness myeloid cells. Some patients with COVID-19 develop severe immune Might reduce incidence of related reactions that can cause edema, coagulopathy, and lung damage, health complications resulting in acute hypoxic respiratory failure. GM-CSF is a cytokine involved in antiviral immunity, innate immune responses, and Might improve population health promoting lung repair. A 2014 compassionate use study found that outcomes if mechanical ventilator GM-CSF had beneficial effects in patients (n = 6) with pneumonia- shortages are minimized associated acute respiratory distress syndrome (ARDS) due to various Might lessen health care costs if pathogens, including significant improvement in oxygenation and length of hospitalization is reduced about a 40% mean increase in lung compliance 10 days post-GM-CSF and fewer intensive care resources inhalation. Sargramostim is being evaluated in a phase 2 trial with 60 are needed COVID-19-positive patients and is estimated to be completed in Might contribute to increased November 2020; a phase 4 trial has an estimated completion of inflammatory response, a potential October 31, 2020. The phase 4 trial will randomly assign 80 patients driver of COVID-19 pathogenesis with COVID-19-related acute hypoxic respiratory failure to treatment with either sargramostim for 5 days through inhalation via mesh nebulizer (125 μg twice daily) plus standard of care therapy or standard of care therapy alone. Patients in either group exhibiting clinical deterioration may receive intravenous sargramostim. Sargramostim costs about $1447 for a 5-day supply.
SECTION 5. TREATMENTS 58
Title Description Possible areas of impact Possible future impacts
SPI-1005 to treat moderate SPI-1005 (Sound Pharmaceuticals, Inc), is an investigational proprietary Patient outcomes Might reduce COVID-19 severity and to severe COVID-19 oral formulation of the organoselenium compound ebselen that is Health care delivery and progression through dual mechanism purported to have antiinflammatory and antiviral properties and is process of action of antiviral and being investigated to treat moderate to severe COVID-19. Ebselen is a antiinflammatory effects Health care costs small-molecule drug that mimics and induces glutathione peroxidase, Might decrease the burden on the an antioxidant enzyme found in the inner ear, brain, lung, and kidney. It health care system purportedly reduces lung inflammation by decreasing inflammatory oxidants and cytokines. Separately, a study published in April 2020 Might improve understanding of identified ebselen as an inhibitor of the SARS-CoV-2 (severe acute inhibiting coronavirus replication and respiratory syndrome coronavirus 2) main protease (Mpro), an enzyme activity and mitigating required to generate viral proteins essential for viral replication, hyperinflammation to treat suggesting it has potential as a targeted antiviral treatment for COVID- COVID-19 19. Another study published in September 2020 by different Might result in cost savings if the researchers echoed computational findings that ebselen has promise drug cost is outweighed by potential against SARS-CoV-2. Sound Pharmaceuticals is investigating the use of health care costs saved with better oral SPI-1005 to treat 120 adults who have moderate to severe COVID- outcomes, or result in higher costs if 19 in two phase 2 clinical trials with primary completion dates in the drug is more expensive than December 2020. potential health care costs saved
SECTION 5. TREATMENTS 59
Table 5.2.Currently Monitored Topics: 17 Topics
Title Description Possible areas of impact Possible future impacts
Anakinra (Kineret) for Anakinra (Kineret) is an interleukin-1 receptor antagonist approved by Patient outcomes Might reduce mechanical ventilation treating COVID-19 with FDA for treating rheumatoid arthritis and cryopyrin-associated periodic Population health time and increase survival in patients acute respiratory distress syndromes. It is also under study for treating COVID-19. Some patients with ARDS Health care costs syndrome and with COVID-19 develop a maladaptive inflammatory response that can Might reduce related health hyperinflammation lead to acute lung injury and respiratory insufficiency. Anakinra acts as complications and risk for long-term a competitive antagonist of the cytokine receptor interleukin-1 sequelae receptor type I (IL-1R1), which acts as a driver of proinflammatory signaling. A small, retrospective study of patients with moderate to Might improve population health severe COVID-19-related acute respiratory distress syndrome (ARDS) outcomes if mechanical ventilator reported 21-day survival of 90% for patients (n = 29) receiving high- shortages are minimized dose anakinra (5 mg/kg, twice daily) plus standard of care treatment Might reduce health care costs compared with survival of 56% in a cohort of patients (n = 16) receiving related to length of hospitalization standard of care treatment alone. A second study of patients with and intensive care resources severe COVID-19-related bilateral pneumonia reported that 25% of patients (n = 52) who received anakinra (200 mg/day on days 1 to 3, 100 mg/day on days 4 to 10) required mechanical ventilation or died compared with 73% of patients (n = 44) in a historical control group. Additionally, multiple studies involving anakinra treatment for patients with COVID-19 are registered at the National Library of Medicine trial registry, including a large multicenter randomized trial in France (ANACONDA; NCT04364009) with a primary completion date in October 2020.
SECTION 5. TREATMENTS 60
Title Description Possible areas of impact Possible future impacts
Anti-GM-CSF monoclonal Some patients with COVID-19 experience an inflammatory condition Patient outcomes Might reduce mechanical ventilation antibodies for treating leading to pulmonary dysfunction and cardiovascular events thought to Population health time and increase survival in patients COVID-19 contribute to COVID-19-related death. Patients with COVID-19 exhibit with acute respiratory distress Health care costs elevated levels of various proinflammatory cytokines, including Might reduce related health granulocyte-macrophage colony-stimulating factor (GM-CSF). complications and risk for long-term Therefore, investigators are studying several investigational anti-GM- sequelae CSF monoclonal antibodies as potential treatments for COVID-19, including gimsilumab, lenzilumab, mavrilimumab, namilumab, and Might improve population health plonmarlimab (TJM2). Limited clinical data are available for use of these outcomes if mechanical ventilator antibodies in treating COVID-19. Data have been published from a shortages are minimized nonrandomized pilot trial of 13 non–mechanically ventilated patients Might reduce health care costs if with COVID-19 pneumonia treated at a single center in Italy. Compared length of hospitalization is reduced with a 26-patient matched control group, mavrilimumab-treated and fewer intensive care resources patients exhibited increased rates of clinical improvement at day 28 are needed (100% vs 65%; p = .030), reduced incidence of death (0% vs 27%; p = .086), and reduced rates of mechanical ventilation (8% vs 35%; p = .14). Additionally, data have been published on the initial clinical use of lenzilumab. However, further study in larger, randomized trials is needed. Multiple anti-GM-CSF monoclonal antibody trials are registered at the National Library of Medicine clinical trials database, including placebo-controlled randomized controlled trials of gimsilumab, lenzilumab, mavrilimumab, and plonmarlimab.
SECTION 5. TREATMENTS 61
Title Description Possible areas of impact Possible future impacts
Anti-interleukin-6 Some patients with COVID-19 experience an inflammatory condition Patient outcomes Might reduce mechanical ventilation monoclonal antibodies for leading to pulmonary dysfunction and cardiovascular events thought to Population health time and increase survival in patients treating patients contribute to COVID-19-related death. Investigators are studying with acute respiratory distress Health care costs hospitalized with severe whether anti-interleukin-6 (IL-6) monoclonal antibodies can treat Might reduce related health COVID-19 COVID-19 by inhibiting the interleukin-1/interleukin-6 (IL-1/IL-6) complications and risk for long-term pathway thought to be a key driver of this inflammation. Multiple trials sequelae of commercially available (eg, sarilumab, siltuximab, tocilizumab) and investigational (eg, clazakizumab, levilimab, sirukumab) IL-6 pathway– Might improve population health targeting antibodies are ongoing. In July 29, 2020, Roche reported that outcomes if mechanical ventilator the phase 3 COVACTA trial of tocilizumab failed to meet its primary shortages are minimized end point; however, a September 18, 2020, Roche press release Might reduce health care costs if reported that the phase 3 EMPACTA trial of tocilizumab met its primary length of hospitalization is reduced end point of reducing the likelihood of patients needing mechanical or fewer intensive care resources are ventilation. Roche also continues to study tocilizumab in a phase 3 trial needed in combination with remdesivir. Sanofi press releases on July 2, 2020, and September 1, 2020, reported that both US and international phase 3 trials of sarilumab failed to meet their primary end points, and the company has no plans for future trials of sarilumab in COVID-19. Preliminary data on the use of siltuximab in treating patients with COVID-19 are available as a preprint.
SECTION 5. TREATMENTS 62
Title Description Possible areas of impact Possible future impacts
Canakinumab (Ilaris) for Some patients with COVID-19 experience an inflammatory condition Patient outcomes Might reduce mechanical ventilation treating COVID-19 leading to pulmonary dysfunction and cardiovascular events thought to Population health time and increase survival in patients contribute to COVID-19-related death. An interleukin signaling with acute respiratory distress Health care costs pathway involving interleukin-1 (IL-1) and interleukin-6 (IL-6) is thought Might reduce related health to be a key driver of this inflammation, and patients with COVID-19 complications and risk for long-term have exhibited elevated levels of various proinflammatory cytokines, sequelae including interleukin-1 beta (IL-1ß). Therefore, investigators are studying whether the anti-IL-1ß monoclonal antibody canakinumab Might improve population health (Ilaris), intended to block IL-1 signaling, can treat COVID-19. outcomes if mechanical ventilator Canakinumab is commercially available, having been FDA approved to shortages are minimized treat periodic fever syndromes and systemic juvenile idiopathic arthritis. Might reduce health care costs if Data from a small retrospective study of 10 canakinumab-treated length of hospitalization is shortened patients indicated that the drug led to reductions in inflammatory and fewer intensive care resources markers and improvement in oxygenation. Multiple canakinumab trials are needed; however, costs might are registered at the National Library of Medicine trial registry, increase if these expensive drugs are including 2 randomized controlled trials. Novartis is sponsoring a used inappropriately, suggesting the randomized, placebo-controlled trial of a single intravenous infusion of need for clear physician and canakinumab in 450 patients hospitalized for COVID-19 pneumonia pharmacy oversight who are not currently on mechanical ventilation. The trial is scheduled for primary completion in September 2020. The Cleveland Clinic is sponsoring a randomized, placebo-controlled trial of a single intravenous infusion of canakinumab in 45 patients hospitalized for COVID-19 with evidence of acute myocardial injury. The trial is scheduled for primary completion in December 2020.
SECTION 5. TREATMENTS 63
Title Description Possible areas of impact Possible future impacts
Convalescent plasma for Convalescent plasma (CP) obtained from patients who have Patient outcomes Might reduce mechanical ventilation treating COVID-19 recovered from infection with SARS-CoV-2 (severe acute respiratory Population health time and increase survival in patients syndrome coronavirus 2; the virus that causes COVID-19) is under with acute respiratory distress Health care costs study to treat the disease. Plasma is the cell-free liquid component Might reduce related health of blood, which contains high levels of blood proteins that may complications and risk for long-term have both antiviral and immunomodulatory effects. In particular, sequelae neutralizing antibodies against SARS-CoV-2 present in CP might confer passive immunity against the virus. Each donation from a Might improve population health patient recovered from COVID-19 may provide sufficient plasma to outcomes if mechanical ventilator treat up to 4 patients of matching blood type. On August 23, 2020, shortages are minimized FDA issued Emergency Use Authorization (EUA) for CP to treat Might reduce health care costs if hospitalized patients with COVID-19 based largely on experience length of hospitalization is shortened with CP in an FDA expanded access program. Among the first or fewer intensive care resources are 35 322 patients treated in this program, the 7-day mortality rate of needed patients who received CP within 3 days of diagnosis was reported as 8.7% compared with 11.9% in patients who received CP 4 or more days after diagnosis. Additional evidence in support of an effect of CP on mortality comes from a prospective matched cohort study, which reported a significant reduction in 28-day mortality. Conversely, a randomized controlled trial of CP in 103 patients did not demonstrate a significant change in clinical improvement or mortality; however, study authors note that the study was terminated before a sufficient number of patients could be enrolled.
SECTION 5. TREATMENTS 64
Title Description Possible areas of impact Possible future impacts
Dexamethasone to treat Dexamethasone is a corticosteroid being investigated as an intravenous Patient outcomes Might improve patient health severe COVID-19 or oral treatment for severe COVID-19. Hyperinflammation is thought Population health outcomes and increase survival to contribute to acute respiratory distress syndrome (ARDS) in COVID- Health care costs Might reduce the burden on the 19 and the need for mechanical ventilation; thus, use of corticosteroids health care system and the risk of to reduce inflammation in COVID-19 might be beneficial. Preliminary mechanical ventilator shortages clinical trial data suggest dexamethasone significantly lowers 28-day mortality among hospitalized patients receiving either invasive Might decrease health care costs mechanical ventilation or oxygen alone compared with participants associated with hospitalization and receiving standard of care treatment. Similarly, a meta-analysis intensive care resources, especially performed by the World Health Organization showed that systemic because dexamethasone is a widely corticosteroids in those critically ill with COVID-19 was associated with available, inexpensive drug a lower 28-day all-cause mortality compared with standard of care Might improve understanding of treatment or placebo. There have been concerns about potential risks hyperinflammation in COVID-19 and of immunosuppression and increased replication of SARS-CoV-2 the role of antiinflammatory drugs (severe acute respiratory syndrome coronavirus 2), although a clinical for treatment study found no association between early intervention with glucocorticoids and mortality or need for mechanical intervention. Ongoing clinical trials investigating the use of dexamethasone to treat COVID-19 include phase 2/3 (United Kingdom) and phase 2 (United States) trials, which have primary completion dates in December 2021 and December 2020, respectively. Based on available trial dosing information and dexamethasone pricing, a course of COVID-19 treatment with dexamethasone is likely to cost between $9 and $21 per patient.
SECTION 5. TREATMENTS 65
Title Description Possible areas of impact Possible future impacts
Dociparstat for treating Dociparstat is a glycosaminoglycan derivative of heparin being Patient outcomes Might improve patient health COVID-19 investigated by Chimerix (Durham, North Carolina) as an intravenous Population health outcomes and increase survival treatment for COVID-19 in hospitalized adult patients. Health care costs Might reduce the burden on the Hypercoagulability is commonly observed in patients who have health care system and mechanical COVID-19 and is associated with worse outcomes. It might be partly ventilator shortages due to damage to endothelial cells from infection with SARS-CoV-2, the virus that causes COVID-19. Treatment with anticoagulants such Might decrease health costs as heparin has been linked to increased survival in patients who have associated with hospitalization and severe COVID-19. Dociparstat, a derivative of heparin, purportedly intensive care resources reduces excessive inflammation, immune cell infiltration, and Might improve understanding of hypercoagulability associated with poor outcomes in severe COVID- anticoagulation and antiinflammatory 19. It can purportedly be given at larger doses without the same risk drugs in the treatment of COVID-19 for bleeding as heparin. Dociparstat is in a developer-sponsored phase 2/3 clinical trial that intends to enroll more than 500 hospitalized adults who have COVID-19 and acute lung injury requiring supplemental oxygen or noninvasive ventilation. The trial has a primary completion date in February 2021.
EIDD-2801 for treating EIDD-2801 (Ridgeback Biotherapeutics, Miami, Florida; and Merck, Patient outcomes Might improve patient health COVID-19 Kenilworth, New Jersey) is an antiviral drug being investigated to treat Population health outcomes and increase survival COVID-19. It is an orally bioavailable prodrug of EIDD-1931, a Might improve population health ribonucleoside analogue developed to treat respiratory viruses. EIDD- Health care delivery and process outcomes if burden on the health 2801 has demonstrated broad-spectrum antiviral activity in animal care system is reduced models against SARS-CoV-2 (severe acute respiratory syndrome Health care costs coronavirus 2; the virus that causes COVID-19), SARS-CoV (severe acute Might decrease health care costs respiratory syndrome–associated coronavirus), and MERS-CoV (Middle associated with hospitalization and East respiratory syndrome coronavirus). Like remdesivir, another intensive care resources antiviral in development to treat COVID-19, EIDD-2801 targets viral Might provide more convenient RNA polymerase to block successful viral RNA replication. Preclinical dosing compared with intravenous studies suggest that EIDD-2801 might have activity against viral RNA antivirals, which might help shift the polymerase harboring remdesivir resistance mutations. EIDD-2801 is treatment of COVID-19 to the home taken by mouth, which might be more convenient than the intravenous setting sooner route of remdesivir. Ongoing clinical trials of EIDD-2801 to treat COVID-19 include developer-sponsored phase 2 studies in the outpatient setting and the inpatient setting, both with primary completion dates in October 2020.
SECTION 5. TREATMENTS 66
Title Description Possible areas of impact Possible future impacts
Leronlimab for treating Some patients with COVID-19 experience an inflammatory condition Patient outcomes Might reduce mechanical ventilation COVID-19 leading to pulmonary dysfunction and cardiovascular events thought to Population health time and increase survival in patients contribute to COVID-19-related death. The CCL5 (RANTES)-CCR5 with acute respiratory distress Health care costs signaling axis might contribute to this hyperinflammatory response by Might reduce related health promoting the chemotaxis (homing and accumulation) of immune cells, complications and risk for long-term thereby amplifying inflammatory responses. Leronlimab is an sequelae investigational monoclonal antibody that purportedly acts as a C-C chemokine receptor type 5 (CCR5) antagonist, inhibiting CCR5- Might improve population health mediated trafficking of proinflammatory immune cells. A study of 10 outcomes if mechanical ventilator patients treated with compassionate-care leronlimab found reductions shortages are minimized in proinflammatory cytokines (eg, interleukin-6 [IL-6]) and decreased Might reduce health care costs if coronavirus in the blood. Additionally, the developer (CytoDyn, Inc) has length of hospitalization is shortened announced preliminary data from a randomized phase 2 trial of and fewer intensive care resources leronlimab in 84 patients with mild to moderate COVID-19. An are needed additional randomized phase 2/3 trial in 390 patients with severe or critical COVID-19 is ongoing, with primary completion in December 2020. Although leronlimab is not commercially available, it is being developed as a potential treatment for patients with HIV. A Biologic License Application for that indication was submitted to FDA in April 2020; however, the company received a refuse-to-file letter from FDA in July 2020.
SECTION 5. TREATMENTS 67
Title Description Possible areas of impact Possible future impacts
Losartan for treating Losartan, an angiotensin II receptor blocker (ARB), is an FDA-approved Patient outcomes Might reduce illness severity and COVID-19 blood pressure medication being investigated to reduce lung injury Population health increase survival and disease progression in patients who have COVID-19 with or Health care disparities Might improve population health without underlying high blood pressure. ARBs are inhibitors of the outcomes if burden on the health renin-angiotensin system (RAS), a complex hormone system that Health care costs care system is reduced regulates blood pressure and fluid and electrolyte balance. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is thought to disrupt Might reduce health care costs if the RAS (specifically through binding to angiotensin-converting hospitalization can be avoided, enzyme 2 [ACE2] receptors for cellular entry) and increase hospitalization length is shortened, or inflammation, contributing to the various renal, cardiovascular, and fewer intensive care resources are immune symptoms seen in COVID-19. Losartan blocks activation of a needed receptor in the RAS (ie, angiotensin II type 1) involved in stimulating Might improve understanding of the fibrosis and inflammatory processes. It has been shown preclinically to role of the RAS in COVID-19 reduce lung inflammation in SARS-CoV (severe acute respiratory pathology and ACEIs or ARBs as syndrome–associated coronavirus) infection and improve survival in potential treatments avian influenza H5N1 infection. Investigators had concerns that RAS Might complicate care delivery and inhibitors might enhance the infectivity of SARS-CoV-2 by increasing adherence for patients with the number of cellular surface ACE2 receptors. Results of recent hypertension research, published in May 2020 and June 2020, have not observed that effect. Instead, a lower risk of all-cause death in patients with hypertension and COVID-19 who take an ARB or angiotensin- converting enzyme inhibitor (ACEI), another RAS-inhibiting drug, was reported. Multiple ongoing clinical trials in the United States are investigating the use of losartan to treat COVID-19.
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Title Description Possible areas of impact Possible future impacts
Lowering testosterone Researchers at Columbia University Irving Medical Center report that Patient outcomes Might improve survival and other levels to treat coronavirus lowering testosterone may reduce the severity or duration of COVID- Population health patient health outcomes by reducing infection 19. This research shows that SARS-CoV-2 (severe acute respiratory the severity of the illness syndrome coronavirus 2), which causes COVID-19, can be prevented Health care delivery and process Might reduce health care costs if from entering human lung cells by interfering with lung cell expression length of hospitalization is shortened of transmembrane serine protease 2 (TMPRSS2), which is required for Health care costs or fewer intensive care resources are viral entry. Further, the research shows that androgenic and estrogenic needed compounds function as modulators of TMPRSS2 expression. Consequently, the US Department of Veterans Affairs has launched a Might raise quality-of-life concerns phase 2 clinical trial to evaluate the use of a prostate cancer drug, based on adverse effects of hormone degarelix (sold as Firmagon), to treat hospitalized male patients with therapy COVID-19 who are not in intensive care, with primary completion in Might increase treatment costs, December 2020. This drug might increase the production of TMPRSS2 depending on patients' insurance in females and, therefore, is unsuitable for this patient population. coverage
SECTION 5. TREATMENTS 69
Title Description Possible areas of impact Possible future impacts
Monoclonal antibodies Cellular entry of SARS-CoV-2 (severe acute respiratory syndrome Patient outcomes Might reduce mechanical ventilation targeting SARS-CoV-2 spike coronavirus 2), the virus that causes COVID-19, depends on an Population health time and increase survival in patients protein receptor binding interaction between the viral surface spike protein and the cell-surface with acute respiratory distress domain for treating COVID- protein angiotensin-converting enzyme 2 (ACE2). Monoclonal Health care costs syndrome 19 antibodies targeting the spike protein receptor binding domain (RBD) Might reduce related health may interfere with this interaction. These virus-neutralizing antibodies complications and risk for long-term might provide short-term, passive immunity to SARS-CoV-2, potentially sequelae reducing viral load and improving patient outcomes. Neutralizing- antibody treatments include single monoclonal antibodies and Might improve population health cocktails containing 2 or more monoclonal antibodies that bind outcomes if mechanical ventilator nonoverlapping RBD epitopes. Multiple neutralizing-antibody products shortages are minimized have reached clinical trials, including several large randomized Might reduce health care costs if controlled trials of LY-CoV555, REGN-COV2, and VIR-7831. Lilly recently length of hospitalization is shortened announced preliminary data from a trial investigating LY-CoV555 as a and fewer intensive care resources treatment of symptomatic COVID-19 in the outpatient setting. Among are needed; however, costs might 450 patients randomly assigned to 1 of 3 LY-CoV555 doses or placebo, increase if these expensive drugs are only the middle LY-CoV555 dose demonstrated an improvement in the used inappropriately, suggesting the primary end point of change in viral load at 11 days. However, most need for clear physician and patients (including patients receiving placebo) achieved complete viral pharmacy oversight clearance by day 11, and LY-CoV555 reportedly improved viral clearance at an earlier time point (day 3). Additionally, patients receiving LY-CoV555 had a 72% reduction in the risk of hospitalization compared with patients receiving placebo (1.7% vs 6%).
Proteomics to identify Researchers at the University of California, San Francisco, have Patient outcomes Might speed development of new human protein targets for developed a protein interaction map for SARS-CoV-2 (severe acute COVID-19 therapeutics from treating COVID-19 respiratory syndrome coronavirus 2), the virus that causes COVID-19. approved drugs The map might facilitate repurposing of drugs approved or in Might uncover potential treatment development for other indications to treat COVID-19. The team targets for new therapeutic agents identified 66 human proteins or host factor targets and 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds) as potential treatment candidates. Researchers identified 2 drug classes with antiviral activity: messenger RNA (mRNA) translation inhibitors and predicted regulators of the sigma-1 and sigma-2 receptors. Researchers suggest these agents could result in new therapeutic approaches to treat COVID-19.
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Title Description Possible areas of impact Possible future impacts
Remdesivir (Veklury) to Remdesivir (Veklury, Gilead, Foster City, California) is an intravenously Patient outcomes Might reduce COVID-19 disease treat COVID-19 administered antiviral adenosine analogue prodrug that purportedly Population health course length and severity and inhibits the replication of multiple RNA viruses and has demonstrated improve survival in vitro activity against SARS-CoV-2 (severe acute respiratory syndrome Health care delivery and process Might improve population health if coronavirus 2). Clinical trial data have suggested remdesivir is effective the burden on the health care system in reducing time to recovery and risk of death in patients with Health care costs is reduced moderate to severe COVID-19. Data have also suggested a 5-day course of treatment with remdesivir might be just as effective as a 10- Might reduce health care costs day course. Most recently, published data from a trial of patients with related to hospitalization and moderate disease found a clinical benefit with remdesivir in patients intensive care resources receiving a 5-day course but not a 10-day course, stated to have Might improve understanding of unclear clinical importance. Remdesivir received Emergency Use antiviral treatments for Authorization (EUA) from FDA to treat severe COVID-19 in May 2020, COVID-19 which was broadened to include all hospitalized patients with COVID- 19 in August 2020. Gilead submitted a New Drug Application to FDA for remdesivir to treat COVID-19. If approved, remdesivir would be the first FDA-approved treatment for COVID-19. Gilead announced the cost of remdesivir to the US government would be $2340 and the list price would be $3120 per 5-day treatment course. A September 2020 report found that 6 out of 8 hospital systems are using remdesivir in severely ill patients only, despite increased availability of the drug for patients with moderate disease.
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Title Description Possible areas of impact Possible future impacts
RLF-100 (Aviptadil) for RLF-100 (Aviptadil, Relief Therapeutics and NeuroRx, Inc) is a synthetic Patient outcomes Might reduce risk of progression to treating COVID-19-induced human vasoactive intestinal polypeptide (VIP) being investigated to Population health ARDS in patients who have nonacute nonacute lung injury and treat both nonacute lung injury and acute respiratory distress lung injury, shorten mechanical acute respiratory distress syndrome (ARDS) in patients who have COVID-19. FDA has granted Health care costs ventilation time, and increase survival syndrome Fast Track designation and expanded access protocol to RLF-100 to in patients who have ARDS treat respiratory failure in COVID-19. SARS-CoV-2 (severe acute Might reduce health complications respiratory syndrome coronavirus 2) is thought to invade and damage and risk for long-term sequelae type 2 cells in the air sacs of the lungs, releasing inflammatory cytokines and causing impaired production of surfactant, a lipoprotein Might improve population health important for oxygen exchange. This injury to the lungs can progress to outcomes if mechanical ventilator ARDS—difficulty breathing due to fluid accumulation in the lungs— shortages are minimized and burden which can result in respiratory failure and the need for mechanical on the health care system is ventilation. RLF-100 purportedly binds to type 2 cells to inhibit decreased cytokine-mediated inflammation and upregulate surfactant production Might reduce health care costs if to reduce inflammation in the lungs and promote oxygen exchange. In length of hospitalization is shortened a phase 2/3 trial, hospitalized adolescent and adult patients with or fewer intensive care resources are nonacute lung injury receive RLF-100 by inhalation. In a phase 2 trial, needed hospitalized adult patients who have COVID-19-induced ARDS and medical necessity for mechanical ventilation receive RLF-100 intravenously. Topline data is anticipated by the end of 2020. In August 2020, the developers announced preliminary reports of rapid recovery from respiratory failure in more than 15 critically ill COVID-19 patients treated with RLF-100.
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Title Description Possible areas of impact Possible future impacts
TD-0903 for treating acute TD-0903 (Theravance Biopharma, Dublin, Ireland) is an investigational Patient outcomes Might improve patient health lung injury in COVID-19 inhaled janus kinase (JAK) inhibitor intended to prevent the progression Population health outcomes and increase survival of acute lung injury to life-threatening acute respiratory distress Health care costs Might improve population health syndrome (ARDS) in patients with COVID-19. ARDS in COVID-19 is outcomes if it reduces the burden on thought to be caused, in part, by a rapid influx of inflammatory the health care system and decreases proteins called cytokines into the lungs (ie, cytokine storm). This causes the risk of mechanical ventilator severe inflammation and impaired oxygen exchange that can result in shortages the need for mechanical ventilation. Intervening early to block cytokine storm in COVID-19 pneumonia might be critical for survival. TD-0903 Might decrease health costs purportedly broadly inhibits the activity of JAKs that play a central role associated with hospitalization and in cytokine signaling. It is taken in a nebulized form to target intensive care resources hyperinflammation in the lungs specifically and limit suppression of the Might improve understanding of JAK immune system systemically. A developer-sponsored phase 2 study inhibitors and/or inhibiting cytokine enrolling 159 hospitalized COVID-19 patients began in the United storm in acute respiratory illnesses Kingdom and is planned to expand to include US clinical sites. The trial such as COVID-19 has a primary completion date in October 2020.
Tranexamic acid for treating Tranexamic acid is a commercially available antifibrinolytic protease Patient outcomes Might improve patient health COVID-19 inhibitor that is being investigated to treat adults with COVID-19. Health care delivery and outcomes and survival Tranexamic acid, a synthetic analogue of the amino acid lysine, inhibits process Might improve population health the conversion of plasminogen to the protease plasmin as well as the Health care costs outcomes by reducing burden on the activity of plasmin itself. Elevated plasmin is a risk factor for COVID-19 health care system susceptibility. Elevated plasmin may induce a hyperfibrinolytic state, which may contribute to COVID-19 organ damage caused by Might decrease health care costs if misregulation of coagulation. Additionally, plasmin could cleave the hospitalizations are reduced, viral spike protein (a step required for viral entry) and, therefore, hospitalization lengths are shortened, elevated plasmin might increase the infectivity and virulence of SARS- and/or fewer intensive care resources CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that are needed per patient causes COVID-19. Tranexamic acid is in two phase 2 trials at one Might improve understanding of research institute to assess its efficacy for treating adults who have antifibrinolytics used to treat COVID- COVID-19 in the outpatient setting and the non–intensive care 19 inpatient setting. Additionally, a novel formulation of tranexamic acid, LB1148, is being evaluated in a phase 2 trial as a potential therapy for hospitalized patients who have COVID-19 with acute respiratory distress syndrome (ARDS) and lung dysfunction. The cost of generic tranexamic acid is as low as $26 for a 30-day supply (650-mg tablets), and the drug is covered by Medicare.
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Table 5.3. Recently Archived Topics: 1 Topic
Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Baricitinib (Olumiant) to Baricitinib (Olumiant) is an orally dosed janus kinase (JAK) type 1 and type 2 inhibitor that is Although baricitinib is a relatively inexpensive treat COVID-19 FDA approved for treating rheumatoid arthritis. It acts by inhibiting production of oral medication that has an established safety inflammatory cytokines. Researchers at BenevolentAI, a company that uses artificial profile, it is not likely to be highly disruptive to intelligence to find potential disease targets, have identified baricitinib as a potential COVID- how COVID-19 is currently treated. However, 19 treatment. They stated the drug might work by 2 mechanisms: by inhibiting JAK1 and more data are needed to truly assess its efficacy JAK2 and thereby reducing production of proinflammatory cytokines (typically elevated in for treating hospitalized patients with COVID-19 patients with COVID-19) and by inhibiting a kinase, AP2-associated protein kinase 1 (AAK1), and to consider its disruptive potential. involved in a cell trafficking process (clarithrin-mediated endocytosis) that plays a role in viral entry, thereby reducing viral infection. Further, baricitinib might be a better candidate than 2 other FDA-approved JAK inhibitors, fedratinib and ruxolitinib, since it has stronger affinity for inhibiting AAK1. Ongoing US clinical trials include a developer-sponsored (Eli Lilly) phase 3 trial with primary completion in September 2020 and a university-sponsored phase 2/3 trial with primary completion in August 2020. Based on available trial dosing information and pricing for baricitinib, one treatment course for COVID-19 costs approximately $1000.
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Section 6. Vaccines and Prophylaxis: 9 Topics
Table 6.1. Topics Added Since Last Status Report: 6 Topics
Title Description Possible areas of impact Possible future impacts
ARCT-021 vaccine for ARCT-021 (Arcturus Therapeutics) is a lipid particle–encapsulated Patient outcomes Might reduce coronavirus infection preventing SARS-CoV-2 messenger RNA (mRNA) vaccine candidate against coronavirus. The Population health risk and improve patient health infection mRNA vaccine purportedly enters the cytosol of antigen-presenting outcomes cells and stimulates the expression of viral proteins that are capable of Clinician and/or caregiver safety Might reduce the cost of treating inducing host immune responses to prevent future infection. severe infections Specifically, the mRNA vaccine is intended to induce expression of viral Health care delivery and spike protein, a glycoprotein normally expressed on the coronavirus process Might enable relaxing of some social distancing protocols surface and responsible for viral fusion and entry. The mRNA Health care disparities component of the vaccine is self-amplifying, which purportedly Might improve understanding of increases immunogenicity. ARCT-021 is in phase 1/2 development with Health care costs mRNA vaccine technologies primary completion expected in December 2020; the randomized, placebo-controlled study will enroll healthy volunteers (n = 92) aged 21 to 80 years to evaluate the safety and immune response of ARCT-021. The manufacturer reported positive preclinical data in animal models, including 100% seroconversion for virus-neutralizing antibodies against the spike protein after a single 2-µg dose of vaccine as well as a robust T-cell response. Based on the low dose of vaccine required to trigger immune responses, the manufacturer plans to be able to produce hundreds of millions of doses in 2021, if approved by FDA.
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Title Description Possible areas of impact Possible future impacts
AZD1222 (ChAdOx1 nCoV- AZD1222 (ChAdOx1 nCoV-19) is a recombinant, attenuated adenovirus Patient outcomes Might reduce coronavirus infection 19) vaccine for preventing vector vaccine in development by AstraZeneca (licensed from the Population health risk and improve patient health SARS-CoV-2 infection University of Oxford) that was purported to generate a strong immune outcomes response from a single dose without replicating (avoiding an active Clinician and/or caregiver safety Might reduce the cost of treating infection from the vaccine). The modified vector contains the gene for severe infections the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Health care delivery and spike protein, which is expressed on the surface of SARS-CoV-2 and is process Might enable relaxing of some social distancing protocols responsible for viral fusion and entry. AZD1222 purportedly enters the Health care disparities cytosol of antigen-presenting cells and triggers the expression of viral Might not provide the level of spike protein, thereby inducing host immune responses to prevent Health care costs protection hoped for, owing to the future infection. The vaccine is part of the US government’s Operation accelerated approval process Warp Speed. Published phase 1/2 interim findings in healthy volunteers Might have undiscovered adverse (n = 1077) given a single dose of the AZD1222 vaccine or control events, owing to the accelerated vaccine followed by a booster dose of AZD1222 reported a 4-fold approval process increase in SARS-CoV-2 antibodies in 95% of participants 1 month after a single AZD1222 dose. Vaccine-induced T-cell responses against the Might have vaccine shortages, if spike protein peaked on day 14. Neutralizing antibodies were seen in effective, due to limited production 91% and 100% of participants 1 month after 1 and 2 doses, capacity respectively. AZD1222 is in a phase 3 trial in 30 000 adults with primary completion on December 2, 2020.
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Title Description Possible areas of impact Possible future impacts
JNJ-78436735 (Ad26.COV2- JNJ-78436735 (Ad26.COV2-S; Johnson and Johnson) is a recombinant, Patient outcomes Might reduce coronavirus infection S) vaccine for preventing attenuated adenovirus vector vaccine in development by Johnson & Population health risk and improve patient health coronavirus infection Johnson that is purported to generate a strong immune response outcomes from a single dose without replicating (avoiding an active infection Clinician and/or caregiver safety Might reduce the cost of treating from the vaccine). The vector was modified to contain the gene for severe infections the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Health care delivery and spike protein, which is expressed on the surface of SARS-CoV-2 and is process Might enable relaxing of some social distancing protocols responsible for viral fusion and entry. JNJ-78436735 purportedly Health care disparities enters the cytosol of antigen-presenting cells and triggers the Might not provide the level of expression of viral spike protein, thereby inducing host immune Health care costs protection hoped for, owing to the responses to prevent future infection. The vaccine is part of the US accelerated approval process government’s Operation Warp Speed. If effective, a billion doses of Might have undiscovered adverse vaccine might be available during 2021. The vaccine is in a phase 3 events, owing to the accelerated trial with 60 000 adults, conducted in 28 states in the United States as approval process well as 8 other countries where transmission rates are high. Initial results might be available by the end of 2020, with primary Might have vaccine shortages, if completion of the trial on March 10, 2023. effective, due to limited production capacity
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Title Description Possible areas of impact Possible future impacts
Monoclonal antibodies Cellular entry of SARS-CoV-2 (severe acute respiratory syndrome Patient outcomes Might improve individual health targeting SARS-CoV-2 spike coronavirus 2), the virus that causes COVID-19, depends on an Population health outcomes by reducing the risk or protein receptor binding interaction between the viral surface spike protein and the cell surface severity of SARS-CoV-2 infection domain for preventing protein angiotensin-converting enzyme 2 (ACE2). Monoclonal Clinician and/or caregiver safety Might improve frontline health care COVID-19 antibodies targeting the spike protein receptor binding domain (RBD) worker and/or patient safety in the have the potential to interfere with this interaction and are being Health care delivery and health care setting investigated for their ability to prevent SARS-CoV-2 infection in process Might limit the extent of SARS-CoV-2 asymptomatic patients with known SARS-CoV-2 exposure. These virus- Health care disparities neutralizing antibodies might provide short-term, passive immunity outbreaks in workplace or residential against SARS-CoV-2, potentially preventing or limiting viral infection. Health care costs settings These antibodies would likely be used in vulnerable populations such Might increase health disparities as individuals with known exposure to SARS-CoV-2-infected persons. based on socioeconomic status, Neutralizing antibodies in development include single monoclonal owing to likely high cost antibodies and cocktails containing 2 or more monoclonal antibodies that bind nonoverlapping RBD epitopes. Two large randomized controlled trials are currently assessing the safety and efficacy of neutralizing antibodies in the preventive setting. A phase 3 trial is assessing Regeneron’s antibody cocktail REGN-COV2 compared with placebo in 2000 asymptomatic, healthy adults in household contact with a SARS-CoV-2-positive individual. The phase 3 BLAZE-2 trial is assessing Lilly/Abcellera’s antibody LY-CoV555 compared with placebo in 2400 skilled nursing and assisted-living facility residents and staff.
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Title Description Possible areas of impact Possible future impacts
NVX-CoV2373 vaccine for NVX-CoV2373 is a recombinant nanoparticle coronavirus vaccine in Patient outcomes Might reduce coronavirus infection preventing SARS-CoV-2 development by Novavax that purportedly generates a protective Population health risk and improve patient health infection immune response against SARS-CoV-2 (severe acute respiratory outcomes syndrome coronavirus 2). The vaccine consists of a full-length SARS- Clinician and/or caregiver safety Might reduce costs associated with CoV-2 spike protein, which is essential for host receptor binding, viral treating severe infections fusion, and viral entry and, therefore, represents a rational immunogen Health care delivery and with which to develop a protective immune response. NVX-CoV2373 process Might enable relaxing of some social distancing protocols may be coadministered with Novavax’s proprietary Matrix-M1 adjuvant Health care disparities to enhance immune responses. Interim results from a randomized, Might have undiscovered adverse placebo-controlled, phase 1/2 study (n = 131), with estimated Health care costs events, owing to the accelerated completion in December 2020, found that adjuvanted NVX-CoV2373 approval process was well tolerated and able to trigger similar antibody responses at the Might have vaccine shortages, if 5-µg and 25-µg dose groups. Patients given adjuvanted NVX-CoV2373 effective, due to limited production at days 0 and 21 developed anti-spike IgG and neutralizing antibody capacity responses that were 4-fold higher than those found in convalescent sera from patients who recovered from COVID-19. The manufacturer has initiated the phase 2 portion of the ongoing phase 1/2 clinical trial, which will enroll 1500 volunteers in the United States and Australia, with 50% of volunteers being over 60 years old. The manufacturer plans to start phase 3 in fall 2020. The vaccine is part of the US government’s Operation Warp Speed.
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Title Description Possible areas of impact Possible future impacts
Prophylactic heparin Coagulopathy is a common complication of COVID-19 and may lead to Patient outcomes Might decrease hospitalization rates anticoagulation for increased rates of venous thromboembolic events, such as deep vein Population health and increase survival nonhospitalized patients thrombosis and pulmonary embolism, in affected patients. Additionally, Health care costs Might improve population health with COVID-19 extensive microvascular thrombosis in the lungs has been observed in outcomes by reducing the burden on autopsies of COVID-19 patients, suggesting a potential role of the health care system coagulopathy in the pathogenesis of the disease. While guidelines from both the American Society of Hematology and the American College of Might decrease health care costs Chest Physicians recommend that all patients hospitalized with COVID- associated with hospitalization 19 receive anticoagulant thromboprophylaxis, anticoagulation is not Might improve understanding of the routinely prescribed to nonhospitalized patients with COVID-19. The role of anticoagulation in the Thrombosis Research Institute, in collaboration with Sanofi, is treatment of COVID-19 conducting a randomized study to determine the safety and efficacy of Might increase the risk of treatment- prophylactic dosing with low-molecular-weight heparin (LMWH) for induced bleeding events treating newly diagnosed, nonhospitalized, high-risk patients with COVID-19. The trial will randomly assign 1370 patients to treatment with LMWH (enoxaparin) or standard of care and assess rates of hospitalization and mortality. Primary data completion is expected in January 2021.
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Table 6.2. Currently Monitored Topics: 2 Topics
Title Description Possible areas of impact Possible future impacts
BNT162 mRNA vaccines for Pfizer and BioNTech have partnered to develop and manufacture Patient outcomes Might reduce coronavirus infection preventing SARS-CoV-2 BNT162b2, a lipid nanoparticle–encapsulated messenger RNA (mRNA) Population health risk and improve patient health infection vaccine that encodes the viral spike protein. Spike protein is expressed outcomes on the virus surface and is responsible for receptor binding and cellular Clinician and/or caregiver safety Might reduce the cost of treating entry. mRNA vaccines purportedly enter the cytosol of antigen- severe infections presenting cells and induce the expression of viral proteins that can Health care delivery and elicit host immune responses to prevent future infection. The process Might enable relaxing of some social distancing protocols manufacturers have been pursuing 4 vaccine candidates (BNT162a, Health care disparities BNT162b1, BNT162b2, and BNT162c2) to accelerate vaccine Might not provide the level of development and in late July chose to proceed with BNT162b2 as the Health care costs protection hoped for, owing to the phase 3 candidate, based on its systemic tolerability. The vaccine is part accelerated approval process of the US government’s Operation Warp Speed, and if it is effective, the Might have undiscovered adverse manufacturers expect to produce millions of doses by the end of 2020. events, owing to the accelerated Phase 1 trial data of adults receiving 2 doses of BNT162b2 at 21-day approval process intervals found that BNT162b2 elicited dose-dependent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) neutralizing Might have vaccine shortages, if responses 1.6 to 3.8 times that of a COVID-19 human convalescent effective, due to limited production serum panel, measured 7 days after dose 2 of 30 µg. BNT162b2 is capacity being investigated at a 30-µg dose in a phase 2/3 trial in 30 000 healthy adults, with estimated completion in April 2021.
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Title Description Possible areas of impact Possible future impacts
mRNA-1273 vaccine for mRNA-1273 (Moderna, Cambridge, Massachusetts) is a lipid Patient outcomes Might reduce coronavirus infection preventing SARS-CoV-2 nanoparticle– encapsulated messenger RNA (mRNA) vaccine against Population health risk and improve patient health infection coronavirus. It encodes a prefusion stabilized form of the viral spike outcomes protein, which is expressed on the surface of the virus and is Clinician and/or caregiver safety Might reduce the cost of treating responsible for viral fusion and entry into cells. The mRNA vaccine severe infections purportedly enters the cytosol of antigen-presenting cells and triggers Health care delivery and the expression of viral proteins that are capable of inducing host process Might enable relaxing of some social distancing protocols immune responses to prevent future infection. The company reported Health care disparities positive interim phase 1 results after healthy adults (n = 45) were given Might not provide the level of 2 doses of 25 µg, 100 µg, or 250 µg of vaccine at days 1 and 28. Health care costs protection hoped for, owing to the Antibody levels were above those found in convalescent serum by day accelerated approval process 36 after the first dose. Pseudovirus-neutralizing activity was low until Might have undiscovered adverse the second dose, suggesting the need for a 2-dose vaccination events, owing to the accelerated regimen. At day 43, virus-neutralizing activity capable of reducing approval process SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infectivity by 80% was identified in all the participants in the 25-μg and Might have vaccine shortages, if 100-μg groups. On May 12, 2020, FDA granted mRNA-1273 Fast Track effective, due to limited production designation. The mRNA-1273 vaccine is in phase 3 development in capacity adults (n = 30 000) at high risk of SARS-CoV-2 infection, with primary completion in October 2022.
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Table 6.3. Recently Archived Topics: 1 Topic
Title Description Archive reason(s) based on data review and/or stakeholder ratings and comments
Bacille Calmette-Guérin The tuberculosis BCG vaccine might confer nonspecific protective effects against various Vaccines specific to COVID-19 will most likely be (BCG) vaccine for reducing upper respiratory tract infections. With respect to COVID-19, a peer-reviewed study reported released before the end of the BCG study, COVID-19 incidence or that countries with higher BCG vaccination rates had lower peak COVID-19 mortality rates. A lowering the disruptive potential of this vaccine severity in health care second study, available as a preprint, reported that a cohort of Spanish patients in their 40s, greatly. This vaccine is also a stopgap measure workers born during a universal BCG vaccine program in that country, had a lower risk of having that might not be universally accepted at health COVID-19 (relative risk of 0.962) than the same cohort in Italy, which never had a universal care facilities, much like the flu vaccine. BCG vaccine program. Investigators posit that elevated immunity from BCG vaccination might confer improved immune defense against COVID-19 and might be used as a stopgap to help protect health care workers in the absence of an effective COVID-19-specific vaccine. A multicenter, randomized clinical trial is ongoing to determine whether BCG vaccination can protect hospital personnel against SARS-CoV-2 infection or COVID-19 severity. The trial will randomly assign 1800 health care personnel in contact with patients with known or suspected SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection for at least 25 hours a week to a single intradermal injection of the BCG Tice strain or placebo; the trial has an estimated primary completion date in May 2021.
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Appendix. Abbreviations and Acronyms
3D 3-dimensional AAK1 AP2-associated protein kinase 1 ACEI angiotensin-converting enzyme inhibitor ACE2 angiotensin-converting enzyme 2 ADHS Arizona Department of Health Services AI artificial intelligence ARB angiotensin II receptor blocker ARDS acute respiratory distress syndrome BARDA Biomedical Advanced Research and Development Authority BCG Bacille Calmette-Guérin CAC coronary artery calcification CCL5 (RANTES)-CCR5 C-C chemokine ligand 5 (regulated upon activation, normal T-cell expressed, and secreted)-C-C chemokine receptor type 5 CDC Centers for Disease Control and Prevention CLIA Clinical Laboratory Improvement Amendments of 1988 COVID-19 coronavirus disease 2019 CP convalescent plasma CRAC calcium release–activated calcium CRISPR clustered regularly interspaced short palindromic repeats CRP C-reactive protein CT computed tomography CTGF connective tissue growth factor ECMO extracorporeal membrane oxygenation ELISA enzyme-linked immunosorbent assay EPA US Environmental Protection Agency
Appendix. Abbreviations and Acronyms 84
EUA Emergency Use Authorization FDA US Food and Drug Administration FIA fluorescent immunoassay FXIIa factor XIIa GM-CSF granulocyte-macrophage colony-stimulating factor GPS Global Positioning System HCHSS Health Care Horizon Scanning System HEPA high-efficiency particulate air HGF hepatocyte growth factor H-IG hyperimmune immunoglobulin IBQ-R Infant Behavior Questionnaire-Revised IL-1 interleukin-1 IL-1β interleukin-1 beta IL-1/IL-6 interleukin-1/interleukin-6 IL-1R1 interleukin-1 receptor type I IL-6 interleukin-6 IL-7 interleukin-7 IT information technology IVIG intravenous immunoglobulin JAK janus kinase JAK1 janus kinase type 1 JAK2 janus kinase type 2 LMWH low-molecular-weight heparin LVEF left ventricular ejection fraction MERS-CoV Middle East respiratory syndrome coronavirus Mpro SARS-CoV-2 main protease mRNA messenger RNA N95 not resistant to oil mists, filters at least 95% of 0.3 micrometer droplets
Appendix. Abbreviations and Acronyms 85
NGS next-generation sequencing NIH National Institutes of Health NIRL near-infrared light PCORI Patient-Centered Outcomes Research Institute PCR polymerase chain reaction POC point-of-care PPE personal protective equipment PPI proton pump inhibitor RAS renin-angiotensin system RBD receptor binding domain Rhu-pGSN recombinant plasma gelsolin RT-PCR reverse transcriptase polymerase chain reaction SARS severe acute respiratory syndrome SARS-CoV severe acute respiratory syndrome–associated coronavirus SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 SGLT2 sodium glucose cotransporter 2 TMPRSS2 transmembrane serine protease 2 VIP vasoactive intestinal polypeptide
Appendix. Abbreviations and Acronyms 86