PCORI Health Care Horizon Scanning System

-

PCORI Health Care Horizon Scanning System:

Horizon Scanning COVID-19

Supplement High Impact Report

Volume 2, Issue 1

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

Jennifer De Lurio, MS

Marcus Lynch, PhD, MBA

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

Madison Kimball, MS

Maria Middleton, MPH

Melinda Rossi, BA

Kelley Tipton, MPH

Rosemary Walker, MLIS

Andrew Furman, MD, MMM, FACEP

April 2021

HORIZON SCANNING SUPPLEMENT HIGH IMPACT REPORT ● APRIL 2021 iii

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 (Contract No. MSA-HORIZSCAN-ECRI-ENG-

2018.7.12). The findings and conclusions herein 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 it did not provide

opinions on 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.

©2021 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 High Impact Report: Volume 2,

Issue 1. Patient-Centered Outcomes Research Institute; April 2021. Prepared by ECRI under

Contract No. MSA-HORIZSCAN-ECRI-ENG-2018.7.12.

https://www.pcori.org/sites/default/files/PCORI-Health-Care-Horizon-Scanning-System-Protocol-Operations-Manual-COVID-19-Supplement.pdf


mailto:[email protected]

http://www.pcori.org/

HORIZON SCANNING SUPPLEMENT HIGH IMPACT REPORT ● APRIL 2021 iv

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 3 months)

briefly list and describe all COVID-19-related topics identified, monitored, and recently

archived. High Impact Reports (every 4 months) highlight 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 means 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 them by mail to Gowri Raman, MBBS, MS,

Patient-Centered Outcomes Research Institute, 1828 L St, NW, Suite 900, Washington, DC

20036, or by email to [email protected].



mailto:[email protected]

HORIZON SCANNING SUPPLEMENT HIGH IMPACT REPORT ● APRIL 2021 v

Contents

Introduction ....................................................................................................................... 1

Background ............................................................................................................................................................ 1

Horizon Scanning Process Overview ..................................................................................................................... 1

Reporting Period Summary ................................................................................................................................... 4

Chapter 1. Devices ............................................................................................................ 6

Chapter Summary .................................................................................................................................................. 6

Topic Summaries .................................................................................................................................................... 7

Negative-Pressure Tents to Limit Airborne Transmission of Coronavirus .................................................. 7

Negative-Pressure Tents to Limit Airborne Transmission of Coronavirus .................................................. 9

Chapter 2. Identifiable Risk Factors and Prognostic Indicators .................................. 12

Chapter Summary ................................................................................................................................................ 12

Chapter 3. Screening and Diagnostics .......................................................................... 13

Chapter Summary ................................................................................................................................................ 13

Topic Summaries .................................................................................................................................................. 15

Lucira COVID-19 All-In-One Test Kit At-Home Assay to Diagnose COVID-19 ............................................. 15

Population-wide Antibody Testing to Quantify Coronavirus Infection Rates ............................................ 17

Saliva-Based Nucleic Acid Assays to Diagnose COVID-19 ........................................................................... 19

Dual Point-of-Care Nucleic Acid Assays to Diagnose COVID-19 and Influenza ......................................... 22

Existing FDA-Authorized Nucleic Acid–Based Tests With Potential to Help Identify

the SARS-CoV-2 B.1.1.7 Variant .................................................................................................................... 24

Chapter 4. Systems and Management .......................................................................... 27

Chapter Summary ................................................................................................................................................ 27

Topic Summaries .................................................................................................................................................. 29

Post-COVID-19 Recovery Programs ............................................................................................................. 29

COVID-19 Vaccine Allocation Planner .......................................................................................................... 31

Drive-through COVID-19 Vaccination Clinics ............................................................................................... 33

Mobile Health Clinics to Increase Access to COVID-19 Health Services ..................................................... 35

Statewide Surge Line for Patient Load Management During the Coronavirus Pandemic ........................ 37

Multidose Vials to Strengthen Vial Supply Chain During COVID-19 ........................................................... 39

Phone Applications to Manage COVID-19 Vaccine Communications and Scheduling .............................. 41

Surveillance Programs to Identify and Follow the Spread of Emerging SARS-CoV-2 Variants ................. 43

HORIZON SCANNING SUPPLEMENT HIGH IMPACT REPORT ● APRIL 2021 vi

Chapter 5. Treatments .................................................................................................... 45

Chapter Summary ................................................................................................................................................ 45

Topic Summaries .................................................................................................................................................. 47

Dexamethasone for Treating Severe COVID-19 .......................................................................................... 47

Monoclonal Antibodies Targeting SARS-CoV-2 Spike Protein Receptor Binding Domain

for Treating Nonhospitalized Patients With COVID-19 ............................................................................... 49

Nitazoxanide (NT-300) to Treat Mild to Moderate COVID-19 ..................................................................... 52

CD24Fc (MK-7110) for Treating Severe COVID-19 ....................................................................................... 54

Dociparstat for Treating Acute Lung Injury in Severe COVID-19 ................................................................ 55

Proteomics to Identify Human Protein Targets for Treating COVID-19 ..................................................... 57

TD-0903 for Treating Acute Lung Injury in COVID-19 ................................................................................. 59

Chapter 6. Vaccines and Prophylaxis ............................................................................ 62

Chapter Summary ................................................................................................................................................ 62

Topic Summaries .................................................................................................................................................. 63

Moderna COVID-19 Vaccine for Preventing Coronavirus Infection ........................................................... 63

Novavax COVID-19 Vaccine (NVX-CoV2373) for Preventing Coronavirus Infection................................... 65

Variant-Specific Vaccines for Preventing COVID-19 .................................................................................... 67

ARCT-021 (LUNAR-COV19) Vaccine for Preventing SARS-CoV-2 Infection ................................................. 70

JNJ-78436735 (Ad26.COV2-S) Vaccine for Preventing Coronavirus Infection............................................. 72

Pfizer-BioNTech COVID-19 Vaccine for Preventing Coronavirus Infection ................................................ 74

Sanofi-GSK SARS-CoV-2 Vaccine for Preventing SARS-CoV-2 Infection ...................................................... 76

CoVLP Vaccine for Preventing SARS-CoV-2 Infection .................................................................................. 78

References ....................................................................................................................... 81

HORIZON SCANNING SUPPLEMENT HIGH IMPACT REPORT ● APRIL 2021 1

Introduction

Background

Horizon scanning identifies technology and systems innovations that could disrupt or cause

significant shifts in health care. Horizon scanning can identify new (and new uses of existing)

diagnostic tests and procedures, health care delivery innovations, medical devices, mental and

behavioral health interventions, pharmaceuticals, public health and health promotion activities,

rehabilitation interventions, and therapeutic interventions.

Health care horizon scanning has typically informed strategic planning activities. Public and

private entities around the world have long used formal or informal health care horizon scanning

programs for purposes including commercial planning, health services research prioritization,

financial or operational planning, controlled diffusion of technologies, and provision of

information to policymakers, purchasers, and health care providers.

Horizon Scanning Process Overview

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 high

potential to impact patient outcomes—for individuals and populations—in the United States

within the next 12 months.

The PCORI Health Care Horizon Scanning System: Horizon Scanning Protocol and

Operations Manual COVID-19 Supplement (hereafter referred to as the Protocol) details the

methodology and criteria we use to select and report on potential high-impact 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, 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 inform 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 section, the analyst selects from the following

terms (criteria for selection are listed after each term) based on their understanding of the

currently available evidence or, in the absence of hard evidence, their 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 and/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.

A preselected 3-member panel of PCORI HCHSS senior team members rapidly reviews and

votes on each proposed topic for inclusion; 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 survey process.

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 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

their 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 Topic Selection and Reporting Methods

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 cause impact within the next

12 months in the United States are selected for inclusion; however, stakeholder comments must

largely support conclusions suggested by ratings. For topics with borderline ratings, high

variance, or questionable comments, a brief review and vote by a preselected 3-member 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.

Topics selected for inclusion are assigned to analysts for report drafting. An analyst may

request topic-specific searches, if needed. The analyst then writes a summary of the topic,

including highlights, a description of the topic, areas of potential impact, potential outcomes, and

key stakeholder comments. An impact score based on stakeholder ratings is calculated and added

to the summary. Topic summaries are compiled into the report chapter corresponding to the topic’s

content area (ie, devices, identifiable risk factors and prognostic indicators, screening and

diagnostics, systems and management, treatments, and vaccines and prophylaxis). The project

manager reviews each topic summary and writes a chapter introduction. A senior horizon scanning

reviewer and a medical copyeditor then check each chapter before all chapters are compiled into

the High Impact Report. The project manager reviews the report and writes a report introduction

that includes background, an overview of the horizon scanning process specific to the COVID-19

Supplement, a description of the report methodology, and a reporting period summary.

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.

To ensure that content is current, analysts update topics as new information arises. 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.

• Development has ceased or stalled.

• The development timeline has shifted and the product is no longer likely to be available



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.

Reporting Period Summary

The PCORI HCHSS COVID-19 Supplement began operating in May 2020. Since then,

review of about 5000 information leads has led to the identification of 202 COVID-19-related

topics across 6 content areas. As of April 16, 2021, after subjecting potential topics to our

inclusion criteria and selection process, we have selected 186 topics as having potential for

impact. Of them, 75 are being actively monitored in the system; 111 topics have been archived.

The 186 total topics span the 6 COVID-19-related content areas as follows (Figure 1):

• Devices: 23 topics (12%)

• Identifiable risk factors and prognostic indicators: 9 topics (5%)

• Screening and diagnostics: 45 topics (24%)

• Systems and management: 35 topics (19%)

• Treatments: 60 topics (32%)

• Vaccines and prophylaxis: 14 topics (8%)

Figure 1. Percentage of Topics by Content Area


Of the 75 actively monitored topics, we have selected—based on the procedures described in

High-Impact Topic Selection and Reporting Methods—29 topics for inclusion in this report,

distributed across 5 COVID-19-related content areas as follows (Figure 2):

• Devices: 1 topic (3%)

• Screening and diagnostics: 5 topics (17%)

• Systems and management: 8 topics (28%)

• Treatments: 7 topics (24%)

• Vaccines and prophylaxis: 8 topics (28%)

Figure 2. Percentage of Topics Selected for Report by Content Area


Chapter 1. Devices

Chapter Summary

As of March 12, 2021, we were monitoring or had recently archived 6 COVID-19-related

device topics. These topics are listed in the January 2021 PCORI Health Care Horizon Scanning

System: Horizon Scanning COVID-19 Supplement Status Report, Volume 2, Issue 1. All 6 topics

were sent for comment to internal ECRI stakeholders, and each received at least 5 sets of ratings

and comments from stakeholders between May 18, 2020, and March 11, 2021. Additional ratings

and comments might also have been received after March 11, 2021.

Topics Considered for Inclusion in This Report

Table 1.1 lists the topic selected for inclusion in this High Impact Report. The included topic

received, on average, moderately high impact ratings and demonstrated considerable consensus

among stakeholders, as evident in the ratings and comments.

Table 1.1. Included Device Topics

Topic title Potential impact score

Negative-pressure tents to limit airborne transmission of coronavirus 3.2

Table 1.2 lists 5 topics considered, but not selected, for inclusion in this High Impact Report.

Excluded topics received, on average, low to moderate impact ratings and were not considered

by most stakeholder reviewers to have high impact potential. Topics are arranged first in

descending order by potential impact score; topics with the same score are listed alphabetically

by topic title.

Table 1.2. Device Topics Considered but Not Included


Extracorporeal blood filtration to treat COVID-19a 3.0

Transvenous phrenic nerve stimulation to improve ventilator weaninga 3.0

Decontamination systems for reprocessing of single-use N95 respirators 2.8

Nickel foam air filter to reduce the risk of coronavirus transmission 2.8

Reusable silicone respirators to protect against COVID-19 infection 2.3

a Topic was recently archived.


Topic Summaries

We present below a summary on a topic deemed to have moderately high to high impact

potential.

Negative-Pressure Tents to Limit Airborne Transmission of

Coronavirus

Potential Impact Score

Stakeholders reviewing this topic thought that

negative-pressure tents to limit airborne

transmission of coronavirus could have a

moderately high impact on patient-oriented

health care relative to COVID-19 in the United

States within the next 12 months.

Highlights

• Negative-pressure tents can remove enclosed air—including droplets exhaled by the

patient—using an attached vacuum motor and filter it through a high-efficiency

particulate air filter before releasing the air into the surrounding room.

• These portable units might reduce the risk of airborne coronavirus transmission to health

care providers during care, transport, or aerosol-generating procedures.

• They might also reduce the need for expensive negative-pressure rooms in hospitals and

could improve patient throughput.

• In August 2020, FDA rescinded a general Emergency Use Authorization (EUA) for

passive protective barrier enclosures (ie, non–negative-pressure tents) to treat COVID-19

cases, citing risks to both providers and patients. FDA recommends using negative-

pressure barriers instead.

• Stakeholders commenting on this topic thought negative-pressure tents might help reduce

transmission of coronavirus while providing health care workers with a safer work

environment. Although negative-pressure tents cost less than full-sized rooms, the

resources needed to set up these tents and increased vaccine uptake might limit their use.

Description

Negative-pressure rooms can effectively contain the spread of airborne pathogens, but the

number of COVID-19 cases can overload this resource. Portable negative-pressure tents might

reduce the need for negative-pressure rooms, decrease the risk of airborne transmission to

frontline health care providers, and increase patient throughput.1

Compact tents are placed over the patient’s head and shoulders.2-4 Larger designs enclose the

entire patient bed.5,6 Tents are constructed of either clear, rigid plastic or clear, soft plastic over a

reusable frame. Providers reach patients through hand-access ports or slits in the walls. A



vacuum hose connected to the hospital air-evacuation system creates the negative-pressure

environment.1

As of March 15, 2021, FDA had granted 6 EUAs for negative-pressure tents—4 compact

tents2-4 and 2 whole-bed tents5,6—to enhance personal barrier protection for providers during

airway management, medical procedures, or transport of patients with COVID-19. Of added

significance, on August 20, 2020, FDA revoked an umbrella EUA issued on May 1, 2020, that

authorized use of passive protective barrier enclosures (ie, without negative pressure) when

treating patients with confirmed or suspected COVID-19.7,8 FDA cited recent research of

simulated intubations using passive barriers, which suggested they might not reduce and could

increase provider exposure to airborne particles (eg, tearing personal protective equipment,

escape of airborne particles).9,10 Further, passive barriers might increase patient risk by

restricting providers’ mobility in performing procedures quickly or accurately on first

attempts.9,10 Thus, FDA recommended using only negative-pressure protective barrier

enclosures, noting it granted EUAs for multiple negative-pressure tents.7,8.

Possible Areas of Impact

• Clinician and/or caregiver safety

• Health care costs

• Health care delivery and process

• Patient health outcomes

Possible Future Impacts

Portable negative-pressure patient tents might increase the availability of negative-pressure

environments for patients with COVID-19, enhancing protection for frontline health care

providers. The compact units might reduce costs associated with increasing the number of

negative-pressure care environments available and provide benefits in high-volume care delivery

centers, which would be of particular importance in economically disadvantaged areas.


Key Stakeholder Perspectives

Between July 1, 2020, and April 20, 2021, seven ECRI stakeholders, reflecting allied health,

health systems, physician, and research perspectives, provided comments and ratings on this

topic. The list below provides a summary of key stakeholder perspectives.

• Negative-pressure tents might provide an alternative safe environment for health care

professionals to care for COVID-19 patients and reduce the strain on hospital resources

(eg, by eliminating the need for full-size negative-pressure rooms).

• The tent technology might provide more immediate access to negative-pressure

environments during emergency situations (eg, COVID-19 pandemic) since it allows

easy deployment and dismantling of the tent. However, use of the tents is expected to

decrease with increased vaccine uptake.

• Conventional negative-pressure rooms require significant financial expenditures and are

difficult to construct on short notice. Negative-pressure tents might provide a faster, less

expensive way to implement negative-pressure environments for individual patients.

• However, the setup for negative-pressure tents would still increase costs and resources

needed per patient compared with those of standard rooms, which might prevent hospitals

from using these tents.


Negative-Pressure Tents to Limit Airborne Transmission of

Coronavirus


Stakeholders reviewing this topic thought

that negative-pressure tents to limit airborne

transmission of coronavirus could have a


health care relative to COVID-19 in the

United States within the next 12 months.

Highlights

• Negative-pressure tents can remove enclosed air—including droplets exhaled by the

patient—using an attached vacuum motor and high-efficiency particulate air filter, before

releasing the air into the surrounding room.

• These portable units might reduce the risk of airborne coronavirus transmission to health

care providers during care, transport, or aerosol-generating procedures.

• They might also reduce the need for expensive negative-pressure rooms in hospitals and

could improve patient throughput.



• In August 2020, FDA rescinded a general Emergency Use Authorization (EUA) for

passive protective barrier enclosures (ie, non–negative pressure tents) to treat COVID-19

cases, citing risks to both providers and patients. FDA recommends using negative-

pressure barriers instead.

• Stakeholders commenting on this topic thought negative-pressure tents might help reduce

transmission of coronavirus while providing health care workers with a safer work

environment. Although negative-pressure tents cost less than full-sized rooms, the

resources needed to set up these tents might still limit their widespread adoption.

Description

Negative-pressure rooms can effectively contain the spread of airborne pathogens, but the

number of COVID-19 cases can overload this resource. Portable negative-pressure tents might

reduce the need for negative-pressure rooms, decrease the risk of airborne transmission to

frontline health care providers, and increase patient throughput.8

Compact tents are placed over the patient’s head and shoulders.9-11 Larger designs enclose

the entire patient bed.12,13 Tents are constructed of either clear, rigid plastic or clear, soft plastic

over a reusable frame. Providers reach patients through hand-access ports or slits in the walls. A

vacuum hose connected to the hospital air-evacuation system creates the negative-pressure

environment.8

As of mid-November 2020, FDA had granted 5 EUAs for negative-pressure tents—3

compact tents9-11 and 2 whole-bed tents12,13—to enhance personal barrier protection for providers

during airway management, medical procedures, or transport of patients with COVID-19. Of

added significance, on August 20, 2020, FDA revoked an umbrella EUA issued on May 1, 2020,

that authorized use of passive protective barrier enclosures (ie, without negative pressure) when

treating patients with confirmed or suspected COVID-19.14,15 FDA cited recent research of

simulated intubations using passive barriers, which suggested they might not reduce and could

increase provider exposure to airborne particles (eg, tearing personal protective equipment,

escape of airborne particles).16,17 Further, passive barriers might increase patient risk by

restricting providers’ mobility in performing procedures quickly or accurately on first

attempts.16,17 Thus, FDA recommended using only negative-pressure protective barrier

enclosures, noting it granted EUAs for multiple negative-pressure tents.14,15





• Patient health outcomes



Portable negative-pressure patient tents might increase the availability of negative-pressure

environments for patients with COVID-19, enhancing protection for frontline health care

providers. The compact units might reduce costs associated with increasing the number of

negative-pressure care environments available and provide benefits in high-volume care delivery

centers, which would be of particular importance in economically disadvantaged areas.


Between July 1 and July 24, 2020, five ECRI stakeholders—reflecting allied health, health

systems, physician, and research perspectives—offered comments and ratings on this topic. The

list below summarizes key stakeholder perspectives.

• Negative-pressure tents might provide an alternative safe environment for health care

professionals to care for COVID-19 patients and reduce the strain on hospital resources

(eg, by eliminating the need for full-sized negative-pressure rooms).

• The tent technology might provide more immediate access to negative-pressure

environments during emergency situations (eg, COVID-19 pandemic) since it allows

easy deployment and dismantling of the tent.

• Conventional negative-pressure rooms require significant financial expenditures and are

difficult to construct on short notice. Negative-pressure tents might provide a faster, less

expensive way to implement negative-pressure environments for individual patients.

• However, the setup for negative-pressure tents would still increase costs and resources

needed per patient compared with those of standard rooms, which might prevent hospitals

from using these tents.


Chapter 2. Identifiable Risk Factors

and Prognostic Indicators

Chapter Summary

As of March 12, 2021, we were not monitoring any COVID-19-related identifiable risk

factor and prognostic indicator topics. We had previously been monitoring 7 topics, which are

listed in the January 2021 PCORI Health Care Horizon Scanning System: Horizon Scanning

COVID-19 Supplement Status Report, Volume 2, Issue 1. The topics were sent for comment to

internal ECRI stakeholders and received at least 5 sets of ratings and comments from

stakeholders between May 18, 2020, and March 11, 2021. Additional ratings and comments

might also have been received after March 11, 2021.

Internal ECRI stakeholders did not think that any of the 7 topics had moderately high to high

impact potential relative to COVID-19-related patient-oriented health care in the United States

within the next 12 months. All 7 topics have been archived.


Because all 7 COVID-19-related identifiable risk factor and prognostic indicator topics had

been previously archived, no topics were considered for inclusion in this report.


Chapter 3. Screening and Diagnostics

Chapter Summary


screening and diagnostics topics. Seventeen of these topics are listed in the January 2021 PCORI

Health Care Horizon Scanning System: Horizon Scanning COVID-19 Supplement Status Report,

Volume 2, Issue 1; the remaining 5 topics were added to the system subsequent to that report. All

22 topics were sent for comment to internal ECRI stakeholders and received at least 5 sets of

ratings and comments from stakeholders between May 18, 2020, and March 11, 2021. Additional

ratings and comments might also have been received after March 11, 2021.

Five topics included in the previous High Impact Report were excluded from this report after

stakeholders re-reviewed the topics and rated them as having low potential for impact (see

ratings in Table 3.2):

• Accula SARS-CoV-2 point-of-care test to diagnose COVID-19 (incorporated into Point-

of-care nucleic acid–based assays to diagnose COVID-19)

• Employee SARS-CoV-2 testing programs to reopen businesses

• Next-generation sequencing assays to diagnose COVID-19 (2.8)

• Point-of-care rapid breath tests to detect COVID-19 (2.8)

• QIAstat-Dx Respiratory SARS-CoV-2 Panel test to diagnose COVID-19

Of the 22 topics, 5 have been selected for inclusion because internal ECRI stakeholders

thought they have moderately high to high impact potential relative to COVID-19-related

patient-oriented health care in the United States within the next 12 months.



Table 3.1 lists 5 topics selected for inclusion in this High Impact Report. Included topics

received, on average, moderately high to high impact ratings and demonstrated considerable

consensus among stakeholders, as evident in the ratings and comments. Topics are arranged first

in descending order by potential impact score and second in ascending order alphabetically by

topic title.

Table 3.1. Included Screening and Diagnostics Topics


Lucira COVID-19 All-In-One Test Kit at-home assay to diagnose COVID-19a 3.5

Population-wide antibody testing to quantify coronavirus infection rates 3.4

Saliva-based nucleic acid assays to diagnose COVID-19 3.4

Dual point-of-care nucleic acid assays to diagnose COVID-19 and influenza 3.2

Existing FDA-authorized nucleic acid–based tests with potential to help identify the

SARS-CoV-2 B.1.1.7 varianta

3.2

Table 3.2 lists 14 topics considered, but not selected, for inclusion in this High Impact

Report. Excluded topics received, on average, low to moderate impact ratings and were not

considered by most stakeholder reviewers to have high impact potential. Topics are arranged first

in descending order by potential impact score; topics with the same score are listed

alphabetically by topic title.

Table 3.2. Screening and Diagnostics Topics Considered but Not Included


3D-printed nasopharyngeal swabs for COVID-19 testing 3.0

Ellume over-the-counter and at-home assay to diagnose COVID-19 3.0

Assure COVID-19 IgG/IgM Rapid Test Device point-of-care test to detect antibodies

against SARS-CoV-2

2.8

Employee SARS-CoV-2 testing programs to reopen businessesa 2.8

Multigene expression tests to predict COVID-19 before symptom onset 2.8

Next-generation sequencing assays to diagnose COVID-19a 2.8

Point-of-care antigen assays to diagnose COVID-19 2.8

Point-of-care nucleic acid–based assays to diagnose COVID-19a 2.8

Point-of-care rapid breath tests to detect COVID-19 2.8

Serology test kits for quantitative detection of anti-SARS-CoV-2 antibodiesa 2.8

COVID-19 diagnostic test at-home self-collection kits 2.5



CRISPR-based assays to diagnose COVID-19a 2.4

College and university SARS-CoV-2 testing programs to prevent COVID-19 spread

among returning studentsa

2.3

QIAstat-Dx Respiratory SARS-CoV-2 Panel test to diagnose COVID-19 2.3

Artificial intelligence blood test analysis to rule out COVID-19a 2.2

cPass SARS-CoV-2 test to detect neutralizing antibodies against SARS-CoV-2a 2.2

T-cell assay (T-Detect COVID) to identify past COVID-19 infection 1.8


Topic Summaries

We present below 5 summaries on topics deemed to have moderately high to high impact

potential. Topics are arranged first in descending order by potential impact score; topics with the

same score are listed alphabetically by topic title.

Lucira COVID-19 All-In-One Test Kit At-Home Assay to Diagnose

COVID-19



Lucira COVID-19 All-In-One Test Kit at-

home assay to diagnose COVID-19 could have

a moderately high to high impact on patient-

oriented health care relative to COVID-19 in

the United States within the next 12 months.

Highlights

• The Lucira COVID-19 All-In-One Test Kit is the first COVID-19 test granted

Emergency Use Authorization (EUA) by FDA for use in the home setting as well as in

point-of-care (POC) settings.

• The test requires a prescription from a health care provider for home use in patients aged

14 years or older who are suspected of having COVID-19. Patients testing positive

should follow up with their health care provider and are recommended to self-quarantine.

• Lucira costs about $50 per test and includes a single-use, battery-operated unit; a nasal

swab; a sample vial; and a plastic disposal bag. Based on results from 51 samples, the

manufacturer claims that the test yields laboratory-quality results in about 30 minutes.

• If Lucira shows comparable accuracy to standard-of-care tests, it might lower the burden

on testing centers and shift care to an at-home setting, which might also expand to

airports, long-term health care facilities, schools, and workplaces.



Description

The Lucira COVID-19 All-In-One Test Kit (Lucira Health, Inc, Emeryville, California) is the

first coronavirus test granted EUA for use in the home setting by FDA.11 It is a low-complexity,

portable loop-mediated isothermal amplification assay that amplifies and detects viral nucleic

acids.12

A health care provider prescribes the test for home use in patients aged 14 years or older who

are suspected of having COVID-19. The test is also intended for use in POC settings, including

temporary screening facilities, physician offices, laboratories, urgent care, and long-term nursing

facilities.13,14 The Lucira COVID-19 test includes a single-use, battery-operated testing unit; a

nasal swab; a sample vial; and a plastic disposal bag.14

According to Lucira Health, Lucira COVID-19 requires a small sample volume to yield

laboratory-quality results in about 30 minutes and is expected to cost about $50 per kit.15 Patients

who test positive are recommended to self-quarantine and follow up with their health care

provider.

The Lucira COVID-19 package insert claims that the test’s performance was evaluated in 51

samples also tested with an FDA-authorized coronavirus test.13,14 Compared to this reference

standard, Lucira COVID-19 showed a positive percent agreement of 94% and a negative percent

agreement of 98%.14




• Health care disparities

• Patient outcomes

• Population health


As the pandemic continues, communities are beginning to accept that they will have to

coexist with COVID-19 to prevent complete lockdowns. In addition to safety measures, such as

mask wearing and social distancing, regular and on-demand testing is used to identify infected

and uninfected individuals. Reliable home COVID-19 testing has been sought since the

pandemic started, to quickly and conveniently identify infected individuals while limiting

exposure to others. Lucira offers fast turnaround times, convenient at-home testing, reliable

accuracy, and a competitive price.14,15

While testing at central laboratories is standard of care, people have to wait several days to

receive test results. For many, waiting for results in self-isolation is not feasible; thus, rapid and

reliable tests are needed. Similar to rapid POC tests, Lucira might reduce the testing burden on

central laboratories. However, Lucira’s at-home testing feature allows individuals to test for

COVID-19 and receive a result within 30 minutes without exposing health care workers to the

virus. People might also use Lucira before joining large crowds such as those in airports,

concerts, stadiums, or movie theaters.16



Between November 25, 2020, and December 4, 2020, six ECRI stakeholders—reflecting

health care generalist, health systems, and research perspectives—provided comments and

ratings on this topic. The list below provides a summary of key stakeholder perspectives.

• Lucira will increase access to testing and might shift COVID-19 management to an at-

home setting by providing purportedly faster results with comparable accuracy to

standard-of-care tests performed at health centers and central laboratories.

• Even though Lucira COVID-19 was validated in a trial that used a small number of

samples (n = 51), as use of the test expands, it might reduce demands on testing centers,

and testing might extend to airports, long-term health care facilities, schools, and

workplaces.

• Despite Lucira’s $50-per-test cost, frequent and widespread testing might increase health

care costs and worsen disparities for low-income individuals who lack financial

assistance.

• At-home testing requires that people voluntarily report positive results to a provider and

that they self-isolate. Some people might not report positive results, fearing social or

economic consequences from isolation protocols.

Population-wide Antibody Testing to Quantify Coronavirus Infection

Rates



population-wide antibody testing to quantify

coronavirus infection rates could have a




Highlights

• Population-wide antibody testing could enable public health agencies to quantify the

prevalence of coronavirus and inform public health policies.

• The Centers for Disease Control and Prevention (CDC) and the National Institutes of

Health (NIH) are conducting population-wide antibody studies using samples from

volunteer blood donors and commercial laboratories to better understand prevalence of

exposure to novel coronavirus at different points in time, locations, and populations in the

United States.

• Stakeholders commenting on this topic thought that widespread serology testing might

help public health professionals understand the spread of coronavirus; however, incorrect

interpretation of negative test results could lead to further spread of COVID-19 if people

stop following public health guidance (eg, wearing masks, social distancing).



• Stakeholders also raised legal, privacy, and security concerns of coronavirus antibody test

results being used to influence policies on employment, travel, and so on.

Description

The COVID-19 pandemic has caused substantial public health and economic crises that make

testing for the prevalence of coronavirus infection, as well as potential immunity, critical to

measure the spread of the disease. Testing for coronavirus-specific antibodies has potential to

serve as a population health screening tool to identify individuals who have been exposed to the

virus regardless of whether they developed symptoms. Widespread serosurveys could provide

data on the extent of COVID-19 spread; however, ECRI recommends against using results from

antibody testing for “immunity passports” or to provide assurance against

reinfection.17,18 Serosurveys could also help identify individuals who can give convalescent

plasma or donate blood or platelets needed for some COVID-19 patients.19

Several large, government agency–sponsored antibody studies are ongoing. The CDC is

collaborating with commercial laboratories to test blood samples submitted for reasons unrelated

to COVID-19. The CDC is also conducting a countrywide COVID-19 study that plans to test

samples from up to 325 000 blood donors in 25 selected cities over 18 months.20 Additionally,

the NIH has launched a similar study of 15 000 participants with no known coronavirus infection

or exposure.21 Results from an antibody positivity (ie, seroprevalence) study in 9028 blood

samples from individuals who had not been diagnosed with COVID-19 showed that there were

nearly 5 undiagnosed cases for every individual diagnosed with COVID-19 as of August 2020.22

In addition to these large-scale government agency–sponsored studies, results from a large

range of US and international seroprevalence studies have been published.23 Of note, a January

2021 study of the prevalence of coronavirus antibodies in 21 424 patients receiving dialysis

across the United States identified a seroprevalence of 18.7% when standardized to the US

adult population.24









Widespread antibody testing might clarify actual infection rates and help more

accurately track the spread of the coronavirus. These data may inform public health efforts

surrounding disease surveillance and management by being incorporated into models of

coronavirus spread, revealing patterns of transmission dynamics, aiding in calculation of the case

fatality rate, and tracking the persistence of coronavirus antibodies over time.

However, seroprevalence studies might misinform public health guidance if the tests generate

high levels of false-positive or false-negative results. In particular, patients who had mild or


asymptomatic disease may not have mounted a large antibody response to treatment and,

therefore, test negative for coronavirus antibodies. Additionally, antibody testing studies using

samples from blood donors or other potentially biased populations might misrepresent true

infection rates if infection rates are different in the targeted population than they are in

the population as a whole.


Between June 25, 2020, and July 6, 2020, five ECRI stakeholders—reflecting health care

generalist, health systems, nursing, and research perspectives—gave comments and ratings on

this topic. The list below summarizes key stakeholder perspectives.

• Serology tests could provide useful information about the spread of COVID-19 and how

long the antibodies prevent reinfection.

• Widespread testing to determine rates of coronavirus infection might guide reopening

policies and procedures, which might help boost the economy and reduce stress and

anxiety in people.

• Because both symptomatic and asymptomatic individuals can spread coronavirus, reliable

and accurate tests are needed to guide suitable public health infection prevention

policies.

• If results are relayed to study volunteers, population-wide testing might increase legal,

privacy, and security concerns if test results influence travel restrictions or if employment

decisions affect specific individuals in the population.

Saliva-Based Nucleic Acid Assays to Diagnose COVID-19



saliva-based nucleic acid assays to diagnose

COVID-19 could have a moderately high impact

on patient-oriented health care relative to

COVID-19 in the United States within the next

12 months.

Highlights

• Saliva-based nucleic acid assay sampling can be performed at home or in health centers

to detect coronavirus nucleic acids in a patient-collected saliva sample—a less invasive

and less costly method than standard nasopharyngeal swab sample collection.

• Results from 2 systematic reviews and 2 published studies found that saliva-based nucleic

acid tests were comparable to nasopharyngeal swab–based testing.

• As of March 2021, FDA has granted Emergency Use Authorization (EUA) to 16 saliva-

based nucleic acid tests for use in laboratories certified under the Clinical Laboratory

Improvement Amendments of 1988 (CLIA). The EUAs for most tests allow patients to

collect samples at home.



• Stakeholders commenting on this topic indicated that, compared with nasopharyngeal

swab–based tests, saliva-based tests have similar accuracy, are more convenient to use,

cost less, and reduce the exposure of health care workers to infected patients.

Description

Saliva-based nucleic acid assays use a process known as polymerase chain reaction (PCR) to

diagnose COVID-19 by detecting coronavirus nucleic acids in a patient’s saliva sample.

Stakeholders evaluated the potential impacts of these saliva-based assays as a single topic

because such tests use similar methods and are expected to yield relatively indistinguishable

results. Compared with nasopharyngeal swab sampling, which is considered the standard of care,

saliva sampling is less invasive, less costly, and can be performed at home or at a health center

without the supervision of a health care worker. Some saliva-based assays have been validated to

use minimally processed saliva samples, obviating the need for a nucleic acid extraction step,

which might save time and testing supplies.25

Results from 2 systematic reviews suggest that saliva-based tests yield similar outcomes to

nasopharyngeal swab–based tests for detecting coronavirus nucleic acids.25 We also identified 2

recently published studies that compared COVID-19 positivity on paired saliva samples and

nasopharyngeal swabs tested by PCR. The studies reported that saliva samples had an overall

agreement between 94% and 99% for detecting coronavirus nucleic acids when compared with

simultaneously collected nasopharyngeal swab samples.26,27

As of March 2021, FDA has granted EUA to 16 saliva-based nucleic acid assays for use in

CLIA-certified laboratories to diagnose COVID-19:

• Advanta Dx SARS-CoV-2 (Fluidigm Corp, South San Francisco, California)28

• Ambry COVID-19 (Ambry Genetics, Aliso Viejo, California)29

• Clarifi COVID-19 (Quadrant Biosciences, Inc, Syracuse, New York)30

• covidSHIELD (University of Illinois, Urbana, Illinois)31

• CRL Rapid Response (Clinical Reference Laboratory, Inc, Lenexa, Kansas)32

• DxTerity SARS-CoV-2 (DxTerity Diagnostics, Inc, Rancho Dominguez, California)33

• Express Gene 2019-nCoV (Express Gene, LLC, Palmetto Bay, Florida)34

• Gravity Diagnostics SARS-CoV-2 (Gravity Diagnostics, LLC, Covington, Kentucky)35

• Infinity BiologiX TaqPath SARS-CoV-2 (Infinity BiologiX, LLC, Piscataway, New

Jersey)36

• NeuMoDx SARS-CoV-2 (NeuMoDx Molecular, Inc, Ann Arbor, Michigan)37

• P23 TaqPath SARS-CoV-2 (P23 Labs, LLC, Little Rock, Arkansas)38

• Phosphorus COVID-19 (Phosphorus Diagnostics, LLC, Secaucus, New Jersey)39

• Rheonix COVID-19 MDx (Rheonix, Inc, Grand Island, New York)40

• SalivaDirect (Yale School of Public Health, New Haven, Connecticut)41

• TRUPCR SARS-CoV-2 (3B Blackbio Biotech India, Ltd, Somerset, New Jersey)42

• Wren Laboratories COVID-19 (Wren Laboratories, Inc, Branford, Connecticut)43










Even though nasopharyngeal swab testing is considered the standard of care, mass testing

requires a large quantity of supplies and trained personnel, which results in an economic and

planning burden at testing sites. Swabbing also causes discomfort to patients, and significant

septum deviation is a contraindication that might discourage some people from getting tested.25

Saliva is a viable noninvasive specimen because it contains liquid, cells, oral bacteria, and

viruses from the oral mucosa and upper airways; however, its occasional stringy and thick

consistency might interfere with test results.25

Similar to nasopharyngeal swab–based tests, saliva-based tests might help triage patients. For

most EUA tests, saliva samples can be collected at home without the supervision of a health care

worker. This might reduce the risk of transmitting the coronavirus to medical staff and other

patients while easing the burden at centers with limited testing supplies and personal protective

equipment.25 The adoption of saliva-based tests might improve patient willingness to undergo

testing, thus increasing testing rates, including among infected patients who are not yet showing

symptoms.26,27


Between August 31, 2020, and October 5, 2020, five ECRI stakeholders—reflecting allied

health, health care generalist, health systems, nursing, and research perspectives—provided

comments and ratings on this topic. The list below summarizes key stakeholder perspectives.

• A clear advantage that saliva-based tests offer over nasopharyngeal swab–based tests is

that allowing patients to collect a specimen at home reduces the exposure of health care

workers to infected patients.

• Because collecting a saliva sample is noninvasive and more convenient than collecting a

nasopharyngeal swab sample, saliva-based testing could improve patient outcomes by

increasing testing rates and reducing COVID-19 spread.

• Although similar in accuracy, saliva-based tests are expected to cost less than

nasopharyngeal swab–based tests, which might reduce disparities and improve care

process and delivery.

• The adoption of saliva-based tests might be hampered by numerous authorized tests and

public test fatigue. It is also unknown whether the assays can detect viral nucleic acids at

all stages of infection.


Dual Point-of-Care Nucleic Acid Assays to Diagnose COVID-19 and

Influenza



that dual point-of-care nucleic acid assays to

diagnose COVID-19 and influenza could

have a moderately high impact on patient-



Highlights

• The infection symptoms that the coronavirus and influenza virus initially cause can be

similar, yet clinicians must be able to differentiate between the 2 respiratory infections to

properly manage patients.

• Point-of-care (POC) nucleic acid–based assays (ie, tests that detect RNA and DNA) have

been developed to diagnose COVID-19 and influenza within an hour.

• FDA has granted Emergency Use Authorization (EUA) to cobas SARS-CoV-2 &

Influenza A/B Nucleic Acid Test and Xpert Xpress SARS-CoV-2/Flu/RSV under a

Clinical Laboratory Improvement Amendments of 1988 (CLIA) certificate of waiver,

which allows these tests to be performed outside of CLIA-certified laboratories.

• Stakeholders commenting on this topic thought that dual POC tests that can rapidly rule

out or identify COVID-19 and influenza could help health care workers manage patients

soon after testing, leading to improved health outcomes.

Description

The flu season in the Northern Hemisphere usually begins in the fall, peaks between

December and February, and tapers around May. Because symptoms for coronavirus and

influenza virus infection can be similar, clinicians must be able to differentiate between the two

to properly manage patients.44

Dual reverse transcription polymerase chain reaction (RT-PCR) assays have been developed

that can diagnose both COVID-19 and influenza. FDA has granted EUA to cobas SARS-CoV-2

& Influenza A/B Nucleic Acid Test (Roche Molecular Systems, Inc, Branchburg, New Jersey)45

and Xpert Xpress SARS-CoV-2/Flu/RSV (Cepheid, Inc, Sunnyvale, California).46 These assays

are intended for use in POC settings, including temporary screening facilities, physician office

laboratories, urgent care, and long-term nursing facilities.

A patient’s nasal or nasopharyngeal sample is loaded into a single-use cartridge or tube that

contains the reagents needed for nucleic acid extraction, amplification, and detection of

coronavirus and influenza virus. The cartridge or tube is placed in an analyzer that controls the

reaction and reports whether viral nucleic acids have been detected. The manufacturers claim

that their assays require a small sample volume and minimal hands-on time to yield accurate

results in less than an hour.47,48



In a study conducted in 375 nasopharyngeal samples, the dual cobas test had a positive

percent agreement (PPA) of 100% and a negative percent agreement (NPA) of 97.4% compared

with a standard-of-care RT-PCR test.49

Although we found no data specific to the performance of Xpert Xpress SARS-CoV-

2/Flu/RSV, we identified 2 multicenter studies suggesting that single-virus and multipanel

versions of Xpert Xpress perform with similar accuracy. These studies compared Xpert Xpress

SARS-CoV-2 with several standard-of-care RT-PCR tests in 483 nasopharyngeal and 88 upper

respiratory tract samples and reported a PPA of 99.5% to 100% and an NPA of 95.8% to

100%.50,51


• Health care delivery






Even before the beginning of the COVID-19 pandemic, respiratory infections caused by

influenza virus and respiratory syncytial virus (RSV) were the leading causes of sickness and

death worldwide in young children, pregnant women, older adults, and patients with other

illnesses.52 As the pandemic continues to overlap with the flu season, it is extremely important to

correctly identify the virus causing a respiratory infection because this will help clinicians

determine a patient’s optimal management.44

Rapid detection of respiratory viruses using POC tests has the potential to decrease the

overall time it takes to receive test results, testing costs, and number of hospitalizations. Accurate

identification of the infectious agent might also decrease the need for follow-up diagnostic

imaging and treatment for opportunistic infections.46 More importantly, rapid testing might allow

health centers to triage infected and uninfected patients on the same day they are tested and

promote early isolation to prevent further spread of the viruses.52-54


Between October 20, 2020, and October 27, 2020, five ECRI stakeholders—reflecting

clinical engineering, health care generalist, health systems, physician, and research

perspectives—provided comments and ratings on this topic. The list below provides a summary

of key stakeholder perspectives.

• Even though mask wearing and social distancing have the potential to lower respiratory

infections, there was an uptick in COVID-19 cases congruent with the beginning of the

flu season. Dual POC tests to distinguish between coronavirus and influenza virus are

critical tools for triaging patients soon after being tested.


• Dual POC tests can pinpoint the infectious agent responsible for a patient’s respiratory

symptoms. This identification might have an enormous impact on population health

because early treatment for the appropriate virus might lead to improved management of

symptoms and fewer hospitalizations.

• Because RSV is responsible for many respiratory infections in children, Xpert Xpress’s

ability to also detect RSV might lead to appropriate care in this cohort. Clear test results

might reduce anxiety in children who might otherwise worry that they have COVID-19

while waiting for subsequent follow-up test results.

• Some concerns exist that manufacturing delays or constraints might limit the availability

of these dual POC tests to a few larger health centers. The adoption of these tests might

also be limited by pandemic fatigue and the availability of many other COVID-19 tests.

Existing FDA-Authorized Nucleic Acid–Based Tests With Potential to

Help Identify the SARS-CoV-2 B.1.1.7 Variant



existing FDA-authorized nucleic acid–based

tests with potential to help identify the SARS-

CoV-2 B.1.1.7 variant could have a moderately

high impact on patient-oriented health care

relative to COVID-19 in the United States


Highlights

• The SARS-CoV-2 B.1.1.7 variant, initially identified in the United Kingdom, might be

more infectious than previous coronavirus strains and might avoid immune responses.

• FDA has identified 2 nucleic acid–based tests with potential to identify individuals likely

to be infected with B.1.1.7. However, possible B.1.1.7 infections will have to be

confirmed by using extensive genetic sequencing.

• Tests that screen for B.1.1.7 infections assess multiple viral genes, but positive cases with

loss of the S gene signal might suggest the presence of the variant.

• Stakeholders commenting on this topic thought that the use of tests to identify possible

B.1.1.7 outbreaks might help health departments prevent spread and guide vaccination

efforts. However, manufacturing capability of these tests is limited, which might decrease

their effect on current testing and prevention measures.



Description

In December 2020, a genetic variant of SARS-CoV-2 with higher transmissibility, B.1.1.7,

was identified in the United Kingdom. It has subsequently been detected in countries around the

world.55

Eight of the 17 mutations accumulated in B.1.1.7 occur in the spike protein–encoding S gene.

Two of these mutations raise potential health concerns: N501Y might increase infectivity, and

69-70del might help the strain evade immune responses. Only sequencing can detect B.1.1.7, but

no tests have been specifically developed to detect B.1.1.7.55,56 FDA has identified 2 authorized

nucleic acid–based tests (Linea COVID-19 Assay Kit [Applied DNA Sciences, Inc, Stony

Brook, New York]57 and TaqPath COVID-19 Combo Kit [Rutgers University, Piscataway, New

Jersey]58) with the potential to identify possible B.1.1.7 infections.59

The S gene mutations in B.1.1.7 lead to loss of an S gene signal from these tests. However,

because the tests assess multiple viral genes, they produce positive signals from other viral

sequences and appropriately detect SARS-CoV-2. This pattern of results (negative for S gene,

positive for other genes) might serve as an indicator of a potential B.1.1.7 infection.60 However,

because variants affecting S gene amplification are not unique to B.1.1.7 (eg, B.1.351 variant

identified in South Africa, P.1 variant identified in Brazil), follow-up testing by more extensive

genetic sequencing is required to confirm the presence of B.1.1.7.56,60








Even though the B.1.1.7 variant was first described in December 2020, evidence suggests

that it had been spreading through the United Kingdom since September 2020. These data,

together with computer modeling, suggest that B.1.1.7 is 70% more transmissible than previous

dominant SARS-CoV-2 strains. The mutations B.1.1.7 has accumulated do not appear to

significantly affect the performance of most FDA-authorized tests. However, proper

identification might be pivotal for preventing B.1.1.7 from spreading and becoming the

coronavirus’s dominant strain.60,61

Early evidence suggests that B.1.1.7 is associated with an increased risk of COVID-19-

related death.62 The use of Linea and TaqPath and similar COVID-19 tests that report the loss of

S gene signal in positive cases to screen for, but not confirm, B.1.1.7 might help suppress the

spread of this variant by predicting possible outbreaks, thereby decreasing COVID-19-related

hospitalizations and deaths. This approach to screen for B.1.1.7 might also cost less than more

extensive sequencing.59



Between January 18, 2021, and February 2, 2021, five ECRI stakeholders—reflecting health

care generalist, health systems, physician, and research perspectives—provided comments and


• Tests such as Linea and TaqPath provide an easy and quick way to identify individuals

who are likely to be infected with B.1.1.7, which will allow time-consuming full

sequencing to be allocated to these specific cases.

• Screening for B.1.1.7 might help local and state health departments provide guidance to

prevent its spread. Identifying possible B.1.1.7 outbreaks might also help direct

vaccination efforts in communities surrounding the outbreak to contain the virus and

prevent it from mutating into new variants.

• The Linea and TaqPath assays are 2 of many tests central laboratories use to diagnose

COVID-19. The companies that manufacture and distribute these tests might have limited

production capabilities, meaning they will be unable to supply laboratories with enough

tests to meet the demand.

• As vaccines continue to roll out, current testing and prevention measures are unlikely to

shift dramatically toward the use of tests that can screen and subsequently confirm

infections with the B.1.1.7 variant.


Chapter 4. Systems and Management

Chapter Summary


systems and management topics. Twelve of these topics are listed in the January 2021 PCORI


Volume 2, Issue 1; the remaining 13 topics were added to the system subsequent to that report.

All 25 topics were sent for comment to internal ECRI stakeholders, and each received at least 5

sets of ratings and comments from stakeholders between May 18, 2020, and March 12, 2021.

One topic included in the previous High Impact Report, Contact tracing software systems to

mitigate coronavirus epidemic scenarios, was archived after stakeholders re-reviewed the topic

and rated it as having low potential for impact; the topic was not considered for inclusion in this

report. From among the remaining 24 topics, 8 topics have been selected that internal ECRI

stakeholders thought have moderately high to high impact potential relative to COVID-19-

related patient-oriented health care in the United States within the next 12 months.



received, on average, moderately high to high impact ratings and demonstrated high consensus

among stakeholders, as evident in the ratings and comments. Topics are arranged first in

descending order by potential impact score and second in ascending order alphabetically by topic

title.

Table 4.1. Included Systems and Management Topics


Post-COVID-19 recovery programs 3.5

COVID-19 vaccine allocation planner 3.4

Drive-through COVID-19 vaccination clinics 3.4

Mobile health clinics to increase access to COVID-19 health services 3.4

Statewide surge line for patient load management during the coronavirus pandemic 3.3

Multidose vials to strengthen vial supply chain during COVID-19 3.2

Phone applications to manage COVID-19 vaccine communications and scheduling 3.2

Surveillance programs to identify and follow the spread of emerging SARS-CoV-2

variants

3.2




considered by most stakeholder reviewers to have high impact potential or were not considered

by most stakeholders to be likely to have an impact within the next 12 months. Topics are

arranged first in descending order by potential impact score; topics with the same score are listed


Table 4.2. Systems and Management Topics Considered but Not Included


Artificial intelligence (AI)-assisted radiographic image assessment for determining

COVID-19 prognosisa

3.2

Drive-through prenatal care model to reduce COVID-19 exposure 3.1

3D-printed face shields to protect against COVID-19 infection 3.0

COVID-19 Testing Impact Calculator 3.0

Emotional PPE Project to facilitate health care worker access to mental health

services

3.0

Machine learning to predict the spread of COVID-19 3.0

Pandemic response strategies to mitigate mental health effects of the COVID-19

pandemic

3.0

Support phone lines to alleviate emotional burden on health care workersb 2.8

Waived insurance copayments, coinsurance, and deductibles to facilitate patient

access to mental health servicesb

2.8

Machine learning algorithm to predict spikes in COVID-19 casesb 2.7

Mental health applications to alleviate mental health effects of COVID-19b 2.7

Public-private partnerships to fast-track COVID-19 treatment and vaccine

developmentb

2.7

Recharge rooms to reduce stress in frontline health care workersb 2.7

Temporary field hospitals to increase capacity during the COVID-19 pandemicb 2.7

Pediatric-specific risk scoring systems to prioritize surgical proceduresb 2.4

Contact-tracing software systems to mitigate coronavirus epidemic scenariosb 2.0

SMART Health Cards to provide digital COVID-19 immunization recordsb 2.0

a Although this topic received a moderately high impact score, it was not included because stakeholders agreed that it would

not likely have an impact in the next 12 months. This topic will be reconsidered for the next report.

b Topic was recently archived.


Topic Summaries




Post-COVID-19 Recovery Programs



that post-COVID-19 recovery programs

could have a moderately high to high impact


COVID-19 in the United States within the

next 12 months.

Highlights

• Multidisciplinary clinical rehabilitation programs might help facilitate recovery from the

long-term effects of COVID-19.

• Several hospitals across the country are setting up post-COVID-19 recovery programs to

accommodate the growing need for continued care in patients experiencing postacute

sequelae of SARS-CoV-2 infection.

• Some programs provide recovery from specific side effects (eg, neurological effects);

other programs have multidisciplinary teams comprising primary care physicians,

pulmonologists, neurologists, mental health professionals, and others.

• Stakeholders commenting on this topic thought that these recovery programs, if carried

out correctly, might improve patient outcomes and provide data for better managing

growing cases of long-term effects of COVID-19.

• Stakeholders expressed concern that these recovery programs may not be covered by

insurance, which might increase financial burden on patients with long-term effects and

their caregivers.

Description

Some individuals who have recovered from COVID-19 have an increased risk of long-term

health problems because of permanent damage to their lungs, heart, kidneys, and brain.63-66 Even

with no detectable damage to these organs, some patients still report lingering and debilitating

symptoms months after clearing the infection. The National Institutes of Health has launched an

initiative to study postacute sequelae of SARS-CoV-2 infection.67

Many hospitals across America are setting up post-COVID-19 recovery programs to

accommodate the growing need for continued care in patients experiencing long-term side

effects from COVID-19.68,69 As of March 2021, more than 67 million people have recovered

from COVID-19.70 Ongoing post-COVID-19 medical, psychological, and rehabilitation

programs may help ensure a full recovery from COVID-19.



Patients who have cleared the viral infection but are still experiencing symptoms can go to

postinfection programs with or without a referral, where they will be screened to identify their

clinical needs and establish a therapeutic plan. The programs consist of multidisciplinary teams

comprising primary care physicians, pulmonologists, neurologists, mental health professionals,

physical/occupational/speech therapists, and others. Some recovery programs address specific

areas such as neurological effects, long-term symptoms in pediatric populations, or respiratory

recovery.71-73 Some programs have implemented new therapeutic approaches to accommodate

the precautions needed to minimize the risk of viral spread, such as negative-pressure rooms for

patients in need of inpatient rehabilitation and isolation as well as therapy through

telemedicine.74






Post-COVID-19 recovery programs might improve management of long-term sequelae from

COVID-19 while increasing knowledge about the long-term effects of COVID-19. These

programs might increase health care costs if clinic visits are not covered by insurance. Patients

might face long wait times due to the lack of recovery programs and increased demand for these

services.


Between November 10, 2020, and November 17, 2020, six ECRI stakeholders, reflecting

health systems and research perspectives, provided comments and ratings on this topic. The list

below provides a summary of key stakeholder perspectives.

• Post-COVID-19 recovery programs might improve health outcomes for patients who

continue to have persistent symptoms after the main course of COVID-19.

• Centralized data collection at these recovery centers can improve understanding of the

long-term effects of COVID-19 and help assess the effectiveness of various treatments.

• Insurance coverage might not be available for patients with postacute sequelae of

COVID-19, which could significantly increase health care costs for patients who may be

unable to work at their previous capacity and their families or caregivers.

• Health care disparities might be reduced if the multidisciplinary recovery programs help

manage various postacute symptoms in one center; however, disparities might increase

due to the lack of recovery programs across the United States.

• Although full recovery from COVID-19 is an important goal for those who have had the

disease, many more recovery programs are desired to expand access to basic care (eg,

maternal health care, mental health) in the general population.


COVID-19 Vaccine Allocation Planner



the COVID-19 Vaccine Allocation Planner

could have a moderately high impact on

patient-oriented health care relative to


next 12 months.

Highlights

• The COVID-19 Vaccine Allocation Planner was created to help state and local officials

and health care leaders plan and implement fair vaccine distribution plans with limited

vaccine availability.

• The standardized tool lets users estimate achievable local vaccine coverage based on

vaccine supplies, vulnerability of local populations, and other variables.

• Some large information technology companies are also starting to offer their own vaccine

allocation planning tools, which could complicate a coordinated national vaccine rollout

strategy if multiple approaches take hold.

• Stakeholders reviewing this topic thought the COVID-19 Vaccine Allocation Planner

could offer a valuable tool for equitable vaccine distribution at the state and local level,

provided that local leaders embrace the planning tool and put its recommendations into

practice.

• Stakeholders also thought the usefulness of this planning tool has diminished over time as

vaccine production and distribution has improved since the shortages seen during the

early vaccine rollout phase.

Description

Early supplies of COVID-19 vaccines are limited. To help with orderly and equitable early

distribution of coronavirus vaccines, researchers at Ariadne Labs (Boston, Massachusetts) and

the Surgo Foundation (Washington, DC) developed the COVID-19 Vaccine Allocation

Planner.75 It is intended to help state and county decision makers distribute early vaccines to the

13 priority populations identified in the Framework for Equitable Allocation of COVID-19

Vaccine guidelines, created by the National Academies of Sciences, Engineering, and

Medicine.76 The vaccine planning tool purportedly lets users obtain estimates of the size of high-

priority populations in their respective geographic regions and consider other factors, such as

community vulnerability, to assign relative weights to groups when considering which groups

should have the highest priority. The allocation planner also helps users estimate the number of

vaccine doses available and the percentage of vaccine coverage achievable under different

scenarios.

Several large information technology companies, including Google (Mountain View,

California), Microsoft (Redmond, Washington), and IBM (Armonk, New York), are reportedly

launching their own digital tools intended to support users with COVID-19 disease forecasting,



vaccine allocation planning, and supply chain logistics.77,78 Multiple approaches could

complicate a smooth national vaccine rollout if a lack of coordination produces overlap or

confusion.

In a related report that has not yet undergone peer review, Massachusetts Institute of

Technology researchers developed a computational model suggesting that optimized COVID-19

vaccine allocation could reduce US deaths by 10% to 25%, or 10 000 to 20 000 deaths, over 3

months.79






The COVID-19 Vaccine Allocation Planner might improve equitable distribution of vaccines

to vulnerable populations by giving local officials tools to implement a more standardized

approach. By providing more transparency early in the vaccine distribution process, the COVID-

19 Vaccine Allocation Planner might increase public acceptance of vaccine distribution plans. If

the allocation planner can help provide for fair distribution during initial vaccine rollouts to

highest-risk groups, the tool might offer a foundation for continued equitable vaccine distribution

among the wider population.


Between November 10, 2020, and April 20, 2021, ten ECRI stakeholders, reflecting

physician, research, health systems, and health care generalist perspectives, provided comments

and ratings on this topic. The list below provides a summary of key stakeholder perspectives.

• A standardized tool to equitably distribute limited vaccine supplies is highly desirable

and could help alleviate disparities, provided the data informing the system are timely,

verifiable, and reliable.

• Comprehensive and effective planning is imperative for equitable and efficient

vaccination efforts that maximize patient access and minimize waste.

• State governments and health care leaders will need to take ownership of the process to

ensure accountability for entering data into the system, using the tools effectively, and

acting accordingly on the results.

• Pressure from outside groups seeking vaccine preference or expressing vaccine

reluctance could complicate vaccine rollout efforts despite good planning.

• With increased vaccine production and distribution after early shortages, the usefulness

for such a planning tool has diminished, especially as eligibility has expanded to age 16

years. However, this model might be helpful for the COVID-19 booster vaccinations

likely needed in the coming months.


Drive-through COVID-19 Vaccination Clinics



that drive-through COVID-19 vaccination

clinics could have a moderately high impact



next 12 months.

Highlights

• Drive-through vaccination sites could accelerate the effort to vaccinate all eligible and

interested individuals now that multiple COVID-19 vaccines are being distributed across

the country after receiving Emergency Use Authorization (EUA) from FDA.

• Several states have begun constructing drive-through vaccine clinics, and some have

already begun administering COVID-19 vaccines to individuals based on their risk

allocation determined by local guidelines.

• Different storage and handling guidelines for the authorized COVID-19 vaccines could

contribute to vaccination site errors, leading to efficacy concerns and poor population

health outcomes.

• Stakeholders thought that drive-through vaccination clinics would speed up vaccination

rates while promoting social distancing to reduce the risk of transmitting COVID-19.

• Stakeholders shared concerns about the limited supply of vaccines, inadequate staffing,

bottlenecks due to a 30-minute postvaccination observation period to monitor adverse

effects, and traffic congestion.

Description

Multiple COVID-19 vaccines have received EUA from FDA and are being distributed across

the United States.80 Drive-through vaccination sites could accelerate the vaccination effort to

meet the nation’s goal of vaccinating all persons who want to be vaccinated. This model was

previously utilized during the swine flu (H1N1) outbreak in 2009 to deliver about 19 000 vaccine

shots in 1.5 days in Louisville, Kentucky.81 The Centers for Disease Control and Prevention has

published considerations for planning drive-through clinics for routine vaccinations, which may

also be useful for distribution of COVID-19 vaccines.82

Several states have begun constructing drive-through clinics. For example, a site in

Montgomery County, Pennsylvania, has a 10-lane carport and has retrofitted shipping containers

for vaccine and medical equipment storage.83 Some other sites across the country have already

begun administering COVID-19 vaccines to individuals based on their risk allocation in mass

drive-through clinics. For example, states like Texas and California have been adding mass

drive-through sites as vaccines are made available.84,85










Drive-through vaccination sites might increase access to vaccination, potentially contributing

to reaching the threshold for herd immunity faster. They might ease the burden on health care

facility resources (eg, personal protective equipment needs) and medical staff since these drive-

through centers would have a different staff pool. There might be efficacy concerns due to the

lack of consistency in storage and handling requirements for the authorized COVID-19 vaccines.

If these vaccination centers are not run well, inefficiencies or errors might lead to poor

population health outcomes.


Between March 4, 2021, and March 8, 2021, five ECRI stakeholders, reflecting health

systems and research perspectives, provided comments and ratings on this topic. The list below

provides a summary of key stakeholder perspectives.

• Drive-through vaccination clinics, if run well, could streamline vaccine administration;

however, the limited supply of vaccines, inadequate staffing, and the 30-minute adverse

effects observation period after vaccine delivery could create bottlenecks.

• This initiative could reduce the risk of COVID-19 transmission since people will not

need to stand in lines, which could reduce health care costs by lowering incidence of

severe illness.

• Drive-through vaccination centers might also decrease health disparities and increase

access for the elderly or those with disabilities who are unable to walk into indoor

vaccination sites.

• These sites may be more feasible to run even in poor weather conditions and might help

reduce appointment cancellations or no-shows, limiting wasted vaccine doses.

• Drive-through clinics would supplement current vaccination centers rather than replace

them and could be useful for disseminating variant boosters; however, they might not be

practical for routine vaccinations after the pandemic.


Mobile Health Clinics to Increase Access to COVID-19 Health Services



mobile health clinics to increase access to

COVID-19 health services could have a




Highlights

• Mobile health clinics—customized motor vehicles that travel to communities to provide

health care—might help meet shortages in COVID-19 health services, including access to

testing, vaccinations, and treatment.

• Aardvark’s health vehicles have 2 to 4 testing windows where staff can administer up to

400 tests a day, comparable to drive-through testing facilities, which are inaccessible for

some people.

• Ease of movement and setup of mobile health clinics might improve implementation of

testing and vaccination initiatives in scattered or harder-to-reach populations.

• Stakeholders commenting on this topic thought that mobile health clinics might benefit

rural areas where COVID-19 cases are surging and health facilities are lacking.

• Stakeholders also thought that the use of mobile clinics depends on the availability of

health care workers to staff these units, costs associated with running the clinics, and the

decision makers who select which areas to serve.

Description

As the COVID-19 pandemic continues, many underserved and rural communities in the

United States still face challenges surrounding access to testing and vaccination. An estimated

2000 mobile clinics (customized motor vehicles that travel to communities to provide health

care) are active and may be able to help meet needs for COVID-19 health services.86

In addition to the existing mobile clinic infrastructure, various companies are offering mobile

clinics. For example, Aardvark Mobile Tours, LLC (Conshohocken, Pennsylvania), offers mobile

health trucks that are equipped with both positive and negative air pressure and the ability to be

Certified Laboratory Improvement Amendments of 1988–certified up to biosafety level 2.87 The

vehicles can be used for rapid testing, vaccinations, and health screenings. The trucks offer a

self-contained space with air conditioning and heating that takes 15 minutes to set up. The easily

sterilized areas and partitions, which separate the nurses conducting the tests from the individuals

receiving them, help maintain the safety of all involved.87 Two to 4 testing windows allow nurses

to administer up to 400 tests a day, similar to drive-through testing facilities, which are

inaccessible to people relying on public transportation. The company supplies an experienced

driver, maintenance, insurance, logistics management, and a program manager so the states

maintain focus on delivering care.87



Additionally, a mobile vaccination clinic in North Carolina expanded its vaccination efforts

to include farmworkers who do not reside in that state.88 Other pilot programs (eg, Curbside

Care) have also begun vaccinating eligible individuals in mobile clinics in rural parts of

Michigan.89









Mobile health clinics might increase access to COVID-19 testing in underserved hot spots

and rural communities, which would improve patient and population health outcomes while

reducing disparities. These clinics might lead to faster implementation of testing initiatives in hot

spots and rural communities, which would inform future public health guidelines. Although the

mobile health clinics would benefit harder-to-reach populations, they might lead to long wait

times if the mobile testing/vaccination site is overwhelmed.


Between December 10, 2020, and January 6, 2021, seven ECRI stakeholders, reflecting

health systems, nursing, physician, and research perspectives, provided comments and ratings on

this topic. The list below provides a summary of key stakeholder perspectives.

• Such direct-to-consumer services might add convenience for populations they serve and

help boost the economy by reducing missed school days, lost wages, and other factors.

• Mobile health clinics might increase access to COVID-19 health services; however, the

usability of mobile clinics hinges on the availability of health care workers to staff these

units, who are at risk of shortages and burnout.

• Economic incentives or resistance to unconventional medical care in rural areas might

influence decision makers’ views on promoting the use of mobile health units in urban

areas, increasing disparities in rural areas.

• These mobile health centers may be able to supplement the shortfalls of the health care

system during the COVID-19 pandemic; however, they may not be sustainable post-

pandemic because of operational costs.


Statewide Surge Line for Patient Load Management During the

Coronavirus Pandemic



the statewide surge line for patient load

management could have a moderately high

impact on patient-oriented health care relative

to COVID-19 in the United States within the

next 12 months.

Highlights

• A statewide patient load balancing system (ie, a surge line), such as the Arizona Surge

Line, can facilitate interfacility transfer of critically ill patients with presumed or

confirmed COVID-19. It might also assist with effectively distributing new staffing

placements from out of state.

• The Arizona system comprises a 24/7 toll-free call line with transfer agents who review

critical care availability for each hospital in the state and transfer calls to a site with

appropriate bed and ventilator capacity.

• Statewide hospital resource utilization hubs might inform public health authorities on

strategies to enhance emergency protocols in future hospital crisis situations.

• Stakeholders commenting on this topic thought that the surge line system had potential to

significantly improve patient care while avoiding staff burnout during COVID-19 surges.

• Stakeholders also thought that some transfers might not be covered by insurance, which

could prevent optimal use of the system and increase costs of care for some patients.

Description

The Arizona Department of Health Services (ADHS) has launched a statewide patient load

balancing system (ie, surge line) to help with transferring patients between facilities during the

COVID-19 public health emergency.90 ADHS hopes that the system will help accommodate

potential surges in the number of COVID-19 cases, which have led some hospitals to cancel or

postpone elective procedures.91

The Arizona Surge Line is a 24/7 toll-free call line for health care providers. For each call, a

surge line transfer agent reviews critical care availability for each hospital in the state and

transfers the call to the appropriate destination, thereby assisting with interfacility transfer of

patients with presumed or confirmed COVID-19 or transfer of patients to post–acute care

facilities.90 The surge line can assist with effectively distributing new staffing placements from

out of state.92 It may also provide clinical consultation if a transfer is declined or delayed.90

Other states (eg, Illinois, Minnesota, Oregon) have created similar statewide hubs with real-

time visibility into bed and ventilator availability across health care systems.93-95

As of December 2020, the Arizona Surge Line had transferred more than 4000 COVID-19

cases to higher levels of care across more than 130 hospitals in Arizona. A 4-month satisfaction



survey suggested that the program successfully expedited transferring patients with COVID-19,

load-balanced patients across Arizona hospitals, improved patient outcomes, and safeguarded the

state’s health care system.96 These results might encourage other states to create

similar programs.









A statewide surge line might help optimize interfacility transfer of presumed or confirmed

COVID-19 patients and could enable health care staff to manage time more effectively by

reducing time to find the right level of care for their patients. These systems might lead to

improved patient outcomes if patients are able to receive appropriate care in a timely manner.

Statewide surge systems might also enhance government policies and public health emergency

guidelines.


Between February 10, 2021, and April 5, 2021, nine ECRI stakeholders—reflecting allied

health, engineering, health care generalist, health systems, physician, and research

perspectives—provided comments and ratings on this topic. The list below summarizes key

stakeholder perspectives.

• Surge line systems could significantly improve patient load management in hospitals,

streamline critical care operations, and enable effective coordination and resource

management among hospitals.

• A statewide surge line system would support optimal care of COVID-19 patients in

critical condition and could therefore improve patient outcomes and reduce risk of

death.

• This system might reduce health care disparities since patients from underserved

locations would have the ability to receive care as well as transportation assistance

postdischarge.

• Interfacility transfer might increase financial burden on families based on insurance

coverage for in-network vs out-of-network hospitals.

• Similar statewide hubs can be developed for improved resource utilization for future

public health emergencies or other situations when the health care system is strained.


Multidose Vials to Strengthen Vial Supply Chain During COVID-19



that multidose vials to strengthen the vial

supply chain during COVID-19 could have a


health care relative to COVID-19 in the


Highlights

• The global demand for vaccinations, combined with an anticipated shortage of medical-

grade glass vials, has prompted vaccine developers to package COVID-19 vaccines in

multidose glass vials containing 8 to 15 doses each.

• Some health experts caution that switching to multidose vials during mass vaccination

programs may increase safety risks for patients and health care providers who administer

vaccinations.

• Stakeholders commenting on this topic thought use of multidose vials increases risk of

infection and improper dosing to patients and risk of injury to providers delivering

vaccinations.

• Stakeholders also thought many providers would likely require refresher training on safe

use of multidose vials since use of these vials for vaccinations has largely been

abandoned in the US health care system.

Description

Drug developers are quickly advancing coronavirus vaccine candidates through clinical trials

and, in parallel, readying manufacturing to prepare for deployment if their candidate proves to be

safe and effective. In the early months of the pandemic, news articles highlighted a shortage of

the medical-grade glass vials needed to distribute vaccines.97,98 A shortage of these glass vials or

syringes could create vaccine access issues for millions of people. Currently, the industry has

decided to use 10-milliliter vials that are capable of holding 8 to 15 doses of coronavirus vaccine

to conserve glass supply. Corning Inc will receive funding from the Biomedical Advanced

Research and Development Authority to accelerate the manufacturing of glass vials for COVID-

19 vaccines and treatments.99,100 Some health experts have expressed concerns about the safety

of multidose vaccine vials, both for patients and for providers giving the vaccinations.101 Single-

dose vaccine vials have a higher per-unit cost than multidose vials, but single-dose vials can

lower risk of cross-contamination and vaccine wastage from improper dosing or storage.102

As of early 2021, further news reports have provided mixed messages from glass

manufacturers regarding the current supply of medical-grade glass vials for vaccines relative to

demand, as more vaccines are now in use in several countries.103-105





• Health care delivery process



Use of multidose vaccine vials during the pandemic might increase access to COVID-19

vaccination for a larger share of the population, potentially shortening the time to achieve herd

immunity to control disease spread. The need to quickly revert to multidose vaccine vials due to

material shortages might change standards for quality and manufacturing throughput in

pharmaceutical packaging. The experience of pivoting between single-dose and multidose

vaccine vials might improve understanding of supply chain management and help inform

preparations for future public health emergencies. Finally, the use of multidose vaccine vials

might increase the risk of treatment-related illness due to cross-contamination of multidose

vaccine vials during mass vaccinations.


Between August 13, 2020, and August 28, 2020, six ECRI stakeholders, reflecting physician,

nursing, research, and allied health perspectives, provided comments and ratings on this topic.

The list below provides a summary of key stakeholder perspectives.

• In the US health care system, single-dose vaccine vials or prefilled, single-use syringes

have largely replaced multidose vials for infection control, medication safety, and

convenience purposes. Thus, many providers will likely require refresher training on

infection prevention and proper draw to measure correct vaccine doses.

• For safety reasons, multidose vials are generally restricted to delivery of multiple doses

of medications to a single patient.

• Beyond the risk of cross-contamination, the use of multidose vaccine vials raises

concerns about proper vaccine handling and storage techniques.

• Shortages of medical-grade glass are likely to affect more than mass vaccination efforts,

since medical-grade glass is used across multiple clinical areas.

• Multidose vials can increase the risk of injury to health care personnel who administer

vaccinations.

• Prefilled, single-dose syringes are the safest option for health care providers and patients

because they create the lowest risk of needlestick injuries, cross-contamination, and

improper dosing.


Phone Applications to Manage COVID-19 Vaccine Communications

and Scheduling



phone applications to manage COVID-19

vaccine communications and scheduling could




Highlights

• The recent availability of multiple COVID-19 vaccines has created a need for broad

campaigns to improve vaccine education, safety and efficacy monitoring, and

appointment scheduling.

• Multiple smartphone apps are in development to educate the public about vaccines and

help health professionals communicate and schedule COVID-19 vaccinations, thus

ensuring an orderly vaccine rollout.

• The GetWellNetwork app communicates locally with users through phones,

smartwatches, and computers to provide information about vaccines and schedule

appointments. Other apps operating at a national level, such as V-Safe, keep track of any

vaccine-related side effects, remind users about second doses, and recommend follow-up

protective measures.

• Stakeholders commenting on this topic thought that if these apps are convenient and use

technology similar to that of other health apps, they might improve vaccine uptake. But if

a large number of apps with limited features and accessibility become available, they

might increase disparities and slow down vaccine rollout.

Description

The availability of multiple FDA-authorized COVID-19 vaccines has created a need for large

public vaccine initiatives that include education campaigns, effectiveness monitoring,

appointment scheduling, and reporting of side effects.80 Several applications are in development

to help government agencies and health care professionals communicate about COVID-19

vaccines and schedule appointments. Some apps are intended to operate at a local and statewide

level, while others are intended for broader use across the country.106,107

LifeBridge Health, a regional health system in the Baltimore metropolitan area,

commissioned GetWellNetwork (Bethesda, Maryland) to develop an app that supports vaccine

distribution, education, and guidance for health care organizations within the state.106 The app

delivers patient communications through smartphones, smartwatches, and computers. It allows

users to schedule vaccine appointments, report side effects, learn more about the vaccines, and

receive reminders about second doses.108 Other vaccine-management app developers include

Skedulo Holdings, Inc (San Francisco, California), Mozzaz Corp (Philadelphia, Pennsylvania),

and RSVPify LLC (Chicago, Illinois).109-111



The Centers for Disease Control and Prevention is providing vaccine recipients access to V-

Safe, a nationwide smartphone app that uses text messages and web surveys to keep track of any

side effects experienced by COVID-19 vaccine recipients. Additionally, the app can notify

patients when it is time to go back for a second dose and remind users to remain engaged in

protective measures even after receiving their vaccinations. Information provided by users

remains confidential and private.107


• Data privacy




With an initial absence of federal protocols for managing COVID-19 vaccinations, state and

local governments have developed their own policies and procedures, using online tools to

educate the public and help administer vaccines. As vaccine rollout continues, additional

smartphone apps have been developed to manage COVID-19 vaccine communications and

scheduling.107,112

Widespread use of smartphone apps might increase public knowledge about these initiatives,

which could, in turn, improve adherence to COVID-19 vaccine dosing schedules. However, the

widespread use of smartphone apps for vaccine scheduling and follow-up could raise concerns

about patient data confidentiality.108,112

If vaccination apps are able to provide unbiased information about the risks and benefits of

vaccination, they might also help engage vaccine-hesitant communities. However, some apps

that lack transparency might support preconceived distrust of vaccines.112


Between January 12, 2021, and January 19, 2021, ten ECRI stakeholders—reflecting allied

health, health systems, nursing, physician, and research perspectives—provided comments and


• Implementation of these apps with COVID-19 vaccine rollout programs could improve

vaccine uptake, if well timed and convenient for users.

• The public might be open to adopting familiar technology for COVID-19 vaccination

efforts because similar apps (eg, appointment reminders, symptom checkers) are

increasingly common across health care networks.

• The usefulness of these apps could be limited if users disregard recommendations or

instructions. Single-language-only apps might limit vaccination efforts and increase

disparities in some communities.

• The use of multiple vaccine-related apps by different health systems or municipalities

might fragment vaccine rollout efforts and slow overall progress compared with more

centralized national health systems.


Surveillance Programs to Identify and Follow the Spread of Emerging

SARS-CoV-2 Variants



surveillance programs to identify and follow the

spread of emerging SARS-CoV-2 variants could


oriented health care relative to COVID-19 in the


Highlights

• In December 2020, three genetic variants of SARS-CoV-2 with higher transmissibility

were identified in the United Kingdom (B.1.1.7), South Africa (B.1.351), and Brazil

(P.1). These variants were subsequently detected in locations around the world.

• The variants appear to be more transmissible than the previously dominant variant, which

might lead to an increase in infections and subsequent COVID-19-related deaths.

Concerns remain that these or future variants might compromise COVID-19 vaccine

efficacy.

• The CDC is working with clinical and national laboratories, state and local health

departments, and genomic sequencing companies to expand the national surveillance

infrastructure for detecting and tracking new variants.

• Stakeholders commenting on this topic thought that surveillance programs for emerging

variants might help prevent their spread, thus improving population health, reducing

costs, and decreasing hospitalizations. However, such programs might not be established

before novel variants emerge and spread.

Description

In December 2020, three genetic variants of SARS-CoV-2 with higher transmissibility were

identified in the United Kingdom (B.1.1.7), South Africa (B.1.351), and Brazil (P.1).55,113 They

have subsequently been detected in countries around the world. The higher transmissibility of

B.1.1.7, B.1.351, and P.1 than the previously dominant coronavirus strain might lead to more

hospitalizations and an increase in COVID-19-related deaths.56,61,62 Moreover, available vaccines

might offer less-than-robust protection against other variants. One such variant is B.1.351, which

contains at least 1 mutation in a region of the spike protein that serves as a key target for

neutralizing antibodies.113 P.1 also harbors mutations in the spike protein that allow the

reinfection of individuals who have recovered from COVID-19.114

Surveillance programs are needed to support public health responses to these emerging

variants. This will require expanded testing and genomic sequencing to identify where the

variants are starting to spread, followed by contact tracing and quarantine programs to decrease

transmission.56 With support from the CDC, the genomic sequencing companies Illumina (San

Diego, California) and Helix (San Mateo, California) will expand the national surveillance

infrastructure to track the emergence and prevalence of new variants.115 The CDC has also



partnered with clinical laboratories, national laboratories, state and local health departments, and

universities to ramp up sequencing-based surveillance and contact tracing.56









The pandemic has strained health care facilities, caused financial hardship, and increased

anxiety. The emergence of variants that are more transmissible than previous SARS-CoV-2

strains might cause even more burden. Early detection of emerging coronavirus strains in

communities might help suppress their spread.56 Working side by side with vaccination

campaigns, surveillance programs can identify variant outbreaks and direct vaccination efforts in

surrounding communities to contain the spread of variants.56,116

Early characterization of these variants suggests that some shared spike protein mutations

might help the coronavirus avoid immune responses in previously infected and vaccinated

individuals.114,116 If vaccination efforts are not sufficient to slow the spread of variants,

surveillance programs might trigger lockdowns and broader restrictions to contain the spread of

variants.116


• Surveillance programs might help provide officials with data to direct the creation of new

public health guidelines that can be applied to prevent the new variants from becoming

dominant coronavirus strains. If these programs help limit coronavirus spread, they might

improve population health, decrease hospitalizations, and reduce health care costs.

• Surveillance programs combined with vaccine monitoring might help determine the

efficacy of vaccines against emergent strains and so direct the plans for targeted

vaccination campaigns.

• Stakeholders noted that the success of these programs relies on having reporting systems

that share information at a national level among the CDC, its partners, and health

officials. However, well-structured systems might not be established before novel

variants arise.

• Surveillance programs might also use resources that are already limited in the

overburdened testing process.


Chapter 5. Treatments

Chapter Summary


treatment topics. Of these topics, 21 are listed in the January 2021 PCORI Health Care Horizon

Scanning System: Horizon Scanning COVID-19 Supplement Status Report, Volume 2, Issue 1;

the remaining 13 topics were added to the system subsequent to that report. All 34 topics were

sent for comment to internal ECRI stakeholders and received at least 5 sets of ratings and

comments from stakeholders between May 18, 2020, and March 11, 2021. Additional ratings and

comments might also have been received after March 11, 2021.

Six topics included in the previous High Impact Report were excluded from this report after

stakeholders re-reviewed the topics and rated them as having low potential for impact (see

ratings in Table 5.2):

• Anakinra (Kineret) for treating COVID-19 with acute respiratory distress syndrome and

hyperinflammation

• Aviptadil (Zyesami, formerly RLF-100) for treating COVID-19

• Convalescent plasma for treating COVID-19

• GM-CSF–inhibiting monoclonal antibodies for treating COVID-19

• Losartan for treating COVID-19

• Remdesivir (Veklury) for treating COVID-19

From among the 34 topics, 7 topics have been selected that internal ECRI stakeholders

thought have moderately high to high impact potential relative to COVID-19-related patient-

oriented health care in the United States within the next 12 months.




received, on average, moderately high to high impact ratings and demonstrated considerable

consensus among stakeholders. Topics are arranged first in descending order by potential impact

score; topics with the same score are listed alphabetically by topic title.

Table 5.1. Included Treatment Topics


Dexamethasone for treating severe COVID-19 3.5

Monoclonal antibodies targeting SARS-CoV-2 spike protein receptor binding domain

for treating nonhospitalized patients with COVID-19

3.3

Nitazoxanide (NT-300) to treat mild to moderate COVID-19a 3.3

CD24Fc (MK-7110) for treating severe COVID-19a 3.2

Dociparstat for treating acute lung injury in severe COVID-19 3.2

Proteomics to identify human protein targets for treating COVID-19 3.2

TD-0903 for treating acute lung injury in COVID-19 3.2

a Topic appears for the first time in this High Impact Report.



considered by most stakeholder reviewers to have high impact potential. Topics are arranged first

in descending order by potential impact score; topics with the same score are listed


Table 5.2. Treatment Topics Considered but Not Included


Tranexamic acid for treating COVID-19 3.1

ANG-3777 to treat patients hospitalized with COVID-19 pneumonia 3.0

Auxora to treat severe COVID-19-associated pneumonia 3.0

Colchicine to treat COVID-19 3.0

CYT107 for treating hospitalized patients with COVID-19-related lymphopenia 3.0

EIDD-2801 for treating COVID-19 3.0

Hyperimmune immunoglobulin for treatment of COVID-19 3.0

Leronlimab for treating COVID-19 3.0

Lowering testosterone levels to treat coronavirus infection 3.0

MultiStem for treating COVID-19-induced ARDS 3.0

Pulmonary surfactant to treat respiratory distress in COVID-19 3.0



Losartan for treating COVID-19 2.8

Machine learning to identify drug candidates to treat COVID-19 2.8

Aviptadil (Zyesami, formerly RLF-100) to treat COVID-19a 2.6

Combination baricitinib and remdesivir to treat COVID-19a 2.6

Fenofibrate to treat COVID-19a 2.6

Prophylactic rivaroxaban anticoagulation for nonhospitalized patients with COVID-

19a

2.6

Quellor (XPro1595) for treating immune-mediated complications due to COVID-19a 2.6

Recombinant plasma gelsolin (rhu-pGSN) for treating COVID-19 pneumoniaa 2.6

SPI-1005 to treat moderate to severe COVID-19a 2.6

rNAPc2 (AB201) for treating COVID-19a 2.4

Remdesivir (Veklury) to treat COVID-19a 2.2

Anti-interleukin-6 monoclonal antibodies for treating patients hospitalized with

severe COVID-19a

2.0

GM-CSF–inhibiting monoclonal antibodies for treating COVID-19a 2.0

Peginterferon lambda-1A (Lambda) for treating COVID-19a 2.0

Anakinra (Kineret) for treating COVID-19 with acute respiratory distress syndrome

and hyperinflammationa

1.8

Convalescent plasma for treating COVID-19a 1.8


Topic Summaries




Dexamethasone for Treating Severe COVID-19



dexamethasone for treating severe COVID-19

could have a moderately high to high impact on

patient-oriented health care relative to COVID-19

in the United States within the next 12 months.



Highlights

• Dexamethasone is a corticosteroid, given orally or intravenously, that has become the

standard of care to treat severe or critical COVID-19.

• Clinical trial data suggest dexamethasone lowers risk of death in patients who require

mechanical ventilation and, to a lesser degree, in patients who require supplemental

oxygen.

• Stakeholders commenting on this topic agreed that dexamethasone has significant

potential to improve patient outcomes by reducing risk of death and is having an impact

in our health care system now.

• Stakeholders thought dexamethasone is likely to be widely used, considering it is

relatively inexpensive, already widely available, and already familiar to prescribers.

Description

Dexamethasone is an orally or intravenously administered corticosteroid that has become a

standard-of-care treatment in patients with severe or critical COVID-19. It is an

immunosuppressant that might mitigate hyperinflammation observed in patients with severe

COVID-19, which is thought to contribute to acute respiratory distress syndrome, multiorgan

failure, and death.117

The National Institutes of Health COVID-19 treatment guidelines recommend the use of

dexamethasone in hospitalized patients with various disease severity levels, including patients

requiring increasing amounts of supplemental oxygen, patients requiring high-flow oxygen or

noninvasive ventilation, and patients requiring mechanical ventilation or extracorporeal

membrane oxygenation.118 The World Health Organization (WHO) similarly recommends the

use of dexamethasone in patients with severe or critical COVID-19.119 These guidelines were

based on findings from multiple trials. Data from the 6424-patient phase 2/3 RECOVERY trial

found that dexamethasone significantly lowered 28-day mortality among those who were

receiving either invasive mechanical ventilation or oxygen alone, but not among those who were

not receiving respiratory support.120 A meta-analysis performed by the WHO before publication

of the RECOVERY data showed that systemic corticosteroids in those critically ill with COVID-

19 were associated with lower 28-day all-cause mortality in 1703 patients across 7 randomized

trials.121

In addition, several clinical trials of dexamethasone are ongoing (eg, phase 3 ACCT-4

trial,122 phase 4 trial123).

Based on available clinical trial dosing information and dexamethasone pricing, a course of

COVID-19 treatment with dexamethasone is likely to cost between $9 and $21 per patient.124







Dexamethasone reduces the risk of death in patients with severe or critical disease who

require mechanical ventilation and supplemental oxygen and might help decrease the need for

intensive care resources such as mechanical ventilation. In turn, population health outcomes

might be improved if better individual patient outcomes translate to lower overall burden on the

health care system and fewer supply shortages (eg, masks, ventilators). At an estimated cost of

less than $21 per treatment course, dexamethasone might result in overall health care cost

savings if hospitalization times are shortened and fewer intensive care resources are needed.


Between February 9, 2021, and February 26, 2021, eight ECRI stakeholders—reflecting

health systems, nursing, and research perspectives—provided comments and ratings on this

topic. The list below summarizes key stakeholder perspectives.

• Dexamethasone has become a standard-of-care treatment for severe and critical COVID-

19 and is having an impact now.

• The drug is highly likely to improve patient outcomes by reducing death, supported by

data published thus far on the intervention.

• Dexamethasone is a relatively inexpensive, widely available, and clinically known drug,

offering potential advantages compared with other treatments (such as cost savings and

prescriber familiarity) that might increase its clinical use.

• Dexamethasone might be the most promising COVID-19 treatment currently available

for improving survival.

Monoclonal Antibodies Targeting SARS-CoV-2 Spike Protein Receptor

Binding Domain for Treating Nonhospitalized Patients With COVID-19



monoclonal antibodies targeting SARS-CoV-2

spike protein receptor binding domain for

treating nonhospitalized patients with COVID-19

could have a moderately high impact on patient-



Highlights

• Monoclonal antibodies targeting coronavirus spike protein (anti-spike monoclonal

antibodies) purportedly treat COVID-19 by interfering with the interaction between the

viral spike protein and its receptor on host cells.

• Multiple randomized controlled trials of anti-spike monoclonal antibody products have

demonstrated their ability to reduce viral loads, reduce rates of hospitalization/emergency

room visits, and/or reduce death rates among nonhospitalized patients.



• Based on these data, FDA has granted Emergency Use Authorization (EUA) to 3 anti-

spike monoclonal antibody products for use in nonhospitalized patients.

• Stakeholders commenting on this topic thought that, based on initial data indicating that

anti-spike monoclonal antibodies reduce the hospitalization rate in patients with mild to

moderate COVID-19, these therapies had the potential to both improve patient health

outcomes and mitigate systemic burdens related to COVID-19 hospitalizations.

• Stakeholders commenting on this topic thought that logistical issues concerning

administering intravenous infusions to coronavirus-infected persons in the outpatient

setting would cause substantial disruption to health care systems and could limit uptake

of these therapies.

Description

Coronavirus cellular entry depends on an interaction between the viral surface spike protein

and a host cell-surface protein, angiotensin-converting enzyme 2.125 Anti-spike monoclonal

antibodies are intended to disrupt this interaction, potentially neutralizing the virus.126

Investigational anti-spike monoclonal antibody products currently under study include both

single-antibody (eg, bamlanivimab [Lilly, Indianapolis, Indiana], VIR-7831 [Vir Biotechnology,

San Francisco, California, and GlaxoSmithKline, Brentford, United Kingdom]) and dual-

antibody (eg, casirivimab/imdevimab [Regeneron, Tarrytown, New York],

bamlanivimab/etesevimab [Lilly]) agents.

Multiple randomized, placebo-controlled trials of anti-spike monoclonal antibody products

have demonstrated efficacy in treating nonhospitalized patients with mild to moderate COVID-

19. Bamlanivimab reduced the rate of hospitalizations or emergency department visits from 10%

to 3% in a 465-patient trial.127,128 Casirivimab/imdevimab reduced the rate of COVID-19-related

medical visits from 9% to 3% in a 799-patient trial.129,130 Bamlanivimab/etesevimab reduced the

rate of COVID-19-related hospitalizations or death from 7% to 2% in a 1035-patient trial.131

VIR-7831 reduced the rate of hospitalization or death by 85% in a 583-patient trial.132

Based on these data, FDA has granted EUA to 3 anti-spike monoclonal antibody products

(bamlanivimab, casirivimab/imdevimab, and bamlanivimab/etesevimab).127,129,131 These EUAs

cover the administration of these products as a single intravenous infusion for treating patients

with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older and

who are at high risk for progressing to severe COVID-19 and/or hospitalization. The products

are not authorized for patients who are hospitalized or require oxygen therapy due to COVID-19.

GlaxoSmithKline and Vir Biotechnology have indicated that they intend to submit an EUA

application for VIR-7831 in the near future.132









Anti-spike monoclonal antibodies have substantial potential to improve patient health

outcomes by reducing the rate at which mild to moderate COVID-19 progresses to more severe,

potentially life-threatening, disease. In addition to these direct effects on patient health, the

potential for these therapies to reduce the number of patients who require hospitalization could

have a positive effect at the population health level by reducing hospital occupancy levels,

potentially allowing for improved care of patients still requiring hospitalization.

Logistical issues surrounding the identification of eligible patients early in the course of their

disease and the intravenous administration of these drugs have the potential to require substantial

changes to health care delivery and processes. Additionally, while the US government has

purchased substantial supplies of these antibodies and is covering their approximately $1250 to

$1500 cost during initial rollout, patients may still be required to cover the cost of the infusion

procedure.133 These factors may have contributed to a perceived underuse of anti-spike

monoclonal antibodies.134


Between February 9, 2021, and February 27, 2021, nine ECRI stakeholders, reflecting health

systems, health care generalist, nursing, physician, and research perspectives, provided

comments and ratings on this topic. The list below provides a summary of key stakeholder

perspectives.

• Anti-spike monoclonal antibodies have substantial potential to improve health outcomes

in nonhospitalized patients at high risk of developing more severe disease. However, the

data are preliminary and may not reflect all potential treatment-related adverse events or

the treatments’ efficacy against newly emerging coronavirus variants.

• The requirement for anti-spike monoclonal antibodies to be administered by intravenous

infusion will be disruptive for health care systems. A shortage of appropriately trained

staff and/or a lack of appropriate physical spaces for isolation of a COVID-19-infected

person during treatment may limit health care facilities’ ability to offer these treatments.

• These therapies are likely to be less readily available in resource-poor communities and,

therefore, have potential to widen health disparities.

• Treatment with anti-spike monoclonal antibodies will impose a substantial cost burden on

the health care system. While these costs may be offset partially by reduced rates of

hospitalizations and associated costs, the impact of these offsets will be constrained by

the large number of patients needing to be treated to prevent a single patient from

developing more severe disease that requires hospitalization.


Nitazoxanide (NT-300) to Treat Mild to Moderate COVID-19



nitazoxanide (NT-300) to treat mild to moderate

COVID-19 could have a moderately high impact



12 months.

Highlights

• Nitazoxanide is an FDA-approved oral antiparasitic drug in development as a repurposed

treatment for mild to moderate COVID-19 in the outpatient setting.

• Nitazoxanide might treat COVID-19 through dual antiviral inhibition of the coronavirus

and the anti-inflammatory action of reducing cytokine release to mitigate

hyperinflammation.

• Stakeholders commenting on this topic thought nitazoxanide has significant potential to

prevent COVID-19 progression to severe disease, thus potentially improving patient

outcomes, reducing hospitalization and associated costs, decreasing health disparities,

and improving clinician safety.

• Stakeholders also thought nitazoxanide is likely to diffuse clinically given its relatively

low cost, established safety profile, and simple storage and administration requirements.

Description

Nitazoxanide is an antiparasitic drug approved by FDA for treating diarrhea caused by

Cryptosporidium parvum and Giardia lamblia (“traveler’s diarrhea”). An extended-release oral

formulation, NT-300 (Romark, LC, Tampa, Florida), is being developed to treat mild to

moderate COVID-19 in the outpatient setting.

Preclinical research suggests nitazoxanide exhibits broad-spectrum antiviral activity against

multiple respiratory viruses, including SARS-CoV-2, and that it suppresses the production of

proinflammatory cytokines.135 Excessive release of proinflammatory cytokines is thought to lead

to hyperinflammation in COVID-19 and correlate with severe disease and poor outcomes.136

No clinical data have been reported yet. NT-300 is being investigated in a developer-

sponsored phase 3, randomized, placebo-controlled clinical trial of 1092 participants with mild

or moderate COVID-19, which had an estimated primary completion date in February

2021.137 In clinical trials, NT-300 is taken by mouth twice daily for 5 days. Based on available

clinical trial dosing and pricing information for 500-mg tablets (300-mg tablets are taken in trials

but are commercially unavailable),138 we estimate a course of nitazoxanide to treat COVID-19

might cost less than $1300.




• Clinician safety


• Health disparities




Nitazoxanide could be the first oral treatment authorized to treat mild to moderate COVID-

19 in the outpatient setting. It might improve patient outcomes by preventing severe COVID-19,

which is associated with poor outcomes and risk of death. It might reduce health disparities

among groups that face disproportionately high rates of progression to severe disease. Less

progression to severe disease might help keep patients with COVID-19 out of the hospital and

thus reduce clinician exposure to the virus, decrease burden on the health care system, and

reduce health care costs associated with hospitalization and intensive care resources.


Between September 1, 2020, and December 8, 2020, seven ECRI stakeholders, reflecting



• Nitazoxanide’s purported antiviral and anti-inflammatory mechanisms of action are

promising and have significant potential to improve patient outcomes by treating

COVID-19 early and preventing disease progression.

• The drug could be an important COVID-19 treatment option, considering current

standard treatment focuses largely on treating patients already hospitalized with moderate

to severe disease rather than preventing disease progression in outpatients with mild

symptoms.

• Nitazoxanide could reduce hospitalizations, thus reducing transmission risk of the

coronavirus to health care personnel and reducing health care costs associated with

hospitalization.

• Aspects of nitazoxanide, including its relatively low cost, established safety profile, and

simple storage and administration requirements, are favorable for potential clinical

uptake.


CD24Fc (MK-7110) for Treating Severe COVID-19



MK-7110 for treating severe COVID-19 could




Highlights

• CD24Fc (MK-7110) is a first-in-class fusion protein that purportedly targets an immune

system checkpoint to modulate the aberrant inflammatory response in patients with

severe COVID-19.

• Clinical trial data suggest that CD24Fc has the potential to reduce time to clinical

recovery and reduce the risk of respiratory failure and death.

• Stakeholders commenting on this topic thought that initial data on CD24Fc suggested it

had substantial potential to improve patient health outcomes in patients with severe

COVID-19.

Description

CD24Fc (MK-7110) is an investigational recombinant fusion protein that consists of the

extracellular domain of mature human CD24 linked to the human immunoglobulin G1 protein.139

It purportedly targets a novel immune pathway checkpoint involving the innate immune system

and is intended to modulate the aberrant inflammatory response to SARS-CoV-2 that is thought

to contribute to disease pathology.140,141

A phase 3, randomized, placebo-controlled trial studying the safety and efficacy of CD24Fc

enrolled 243 patients hospitalized with severe or critical COVID-19.142 In this trial, patients

received an intravenous infusion of CD24Fc or placebo at day 1 in addition to standard of care,

which could include remdesivir and/or dexamethasone. Preliminary data from 203 patients

indicated that, compared with placebo, treatment with CD24Fc improved the likelihood of

clinical recovery by 60%, decreased median time to recovery from 10 days to 6 days, and

reduced the risk of death or respiratory failure by more than 50%.143

CD24Fc is being developed by Merck (Kenilworth, New Jersey), which acquired CD24Fc’s

original developer, Oncoimmune (Rockville, Maryland), in late 2020.144 In December 2020,

Merck entered into a supply agreement with the US government to supply 60 000 to 100 000

doses of the drug during the first half of 2021.145 However, in February 2021, Merck announced

that FDA had indicated a potential Emergency Use Authorization application would need data

beyond those provided by the completed phase 3 trial, likely delaying availability of the drug.146









CD24Fc might reduce risk of death in patients with severe disease and might help reduce the

need for intensive care resources such as mechanical ventilation. In turn, population health

outcomes might be improved if better individual patient outcomes translate to lower overall

burden on the health care system. As a novel biologic drug, CD24Fc is likely to be highly costly;

however, direct drug costs might be offset by reducing the length of hospital stay for some

patients and/or avoiding the need for costly mechanical ventilation.


Between November 5, 2020, and November 16, 2020, five ECRI stakeholders, reflecting



• If the signs of efficacy demonstrated in the initial phase 3 data are confirmed by further

study, CD24Fc has substantial potential to provide an alternative treatment option for

patients with severe COVID-19 and improve outcomes for these patients.

• The signs of efficacy that CD24Fc demonstrated when used in addition to standard-of-

care treatments (eg, dexamethasone, remdesivir), in addition to its ability to be used as a

combination therapy, could promote more widespread use of CD24Fc.

• Availability of a treatment with potential to reduce time to recovery and duration of

hospital stays would have a positive effect on health systems, freeing up resources and

reducing costs associated with hospitalization.

• Further study is needed to confirm the initial signs of efficacy and to identify any

potential adverse effects of the treatment.

Dociparstat for Treating Acute Lung Injury in Severe COVID-19



dociparstat for treating acute lung injury in

severe COVID-19 could have a moderately high

impact on patient-oriented health care relative

to COVID-19 in the United States within the

next 12 months. Potential Impact Score


Highlights

• Dociparstat is a derivative of the anticoagulant heparin that is being investigated as an

intravenous treatment for patients hospitalized with acute lung injury in severe COVID-

19.

• Dociparstat purportedly reduces excessive inflammation, immune cell infiltration, and

hypercoagulability associated with poor outcomes in severe COVID-19.

• Initial reported clinical data suggest treatment with dociparstat, compared with placebo,

might be associated with lower laboratory measures of inflammation and coagulability,

decreased thromboembolic events, and increased survival.

• Stakeholders commenting on this topic thought dociparstat has significant potential to

improve patient outcomes in those with acute lung injury in severe COVID-19 and might

be safer than heparin, which carries significant risk for bleeding.

• Stakeholders also thought dociparstat might be used in combination with other COVID-

19 treatments.

Description

Dociparstat is a derivative of the anticoagulant heparin that is being investigated by Chimerix

(Durham, North Carolina) as an intravenous treatment for hospitalized adult patients who have

acute lung injury associated with severe COVID-19. Hypercoagulability is commonly

observed in patients who have severe COVID-19 and is associated with worse outcomes.147 It

might occur due to damage to endothelial cells from infection with SARS-CoV-2.148 Treatment

with anticoagulants such as heparin has been linked to improved clinical outcomes and increased

survival in patients who have severe COVID-19 with coagulopathy.149,150 Dociparstat

purportedly reduces excessive inflammation, immune cell infiltration, and

hypercoagulability associated with worse outcomes in COVID-19.151 Dociparstat purportedly has

less anticoagulant activity than heparin, allowing it to be given at higher doses for larger anti-

inflammatory effects.152

Dociparstat is in an ongoing phase 2/3 clinical trial enrolling more than 500 hospitalized

adults who have acute lung injury in COVID-19 requiring supplemental oxygen or noninvasive

ventilation.153 Chimerix reported initial topline data in February 2021 from the first cohort of 12

patients (6 dociparstat, 6 placebo).154 Two deaths were reported in the placebo group (at day 2

and post day 28) compared with no deaths reported in the dociparstat group. Normal coagulation

and inflammatory laboratory parameters were observed in the dociparstat group. Two patients in

the placebo group demonstrated significant elevations in these parameters by day 5; one patient

experienced pulmonary embolism with subsequent recovery and the other developed acute

respiratory disease syndrome resulting in death.







Dociparstat might improve patient health outcomes by reducing risk of thromboembolic

events and improving survival. It might reduce hospitalization length and intensive care resource

use, thus decreasing the burden on the health care system and resulting in health care cost

savings. Population health might be improved from better individual patient outcomes and

overall decreased burden on the health care system. The development of dociparstat for treating

COVID-19 might aid in understanding anticoagulation in the treatment of COVID-19 and better

help the formulation of COVID-19 clinical guidelines.


Between June 12, 2020, and June 25, 2020, five ECRI stakeholders, reflecting health

systems, nursing, physician, and research perspectives, provided comments and ratings on this


• Dociparstat has significant potential to improve patient outcomes, considering its

purported mechanisms of action and promising preclinical data.

• If efficacious, dociparstat has potential to decrease health care costs associated with

hospitalization and COVID-19 testing and treatment.

• Dociparstat is likely to be safer and easier to titrate than heparin, which carries significant

risk for bleeding, and might have larger anti-inflammatory effects.

• Dociparstat might be used clinically in combination with medications in other drug

classes, such as biologic immune-modifying agents or antiviral drugs.

Proteomics to Identify Human Protein Targets for Treating COVID-19



proteomics to identify human protein targets for

treating COVID-19 could have a moderately




Highlights

• University of California, San Francisco, researchers have developed a protein map that

helps identify which human proteins interact with proteins in SARS-CoV-2. This tool

might make it easier and faster to identify drugs approved or in development for other

indications that could be repurposed to treat COVID-19.

• Initial findings suggest that several existing drugs, including the hormone progesterone,

antipsychotic drugs, and antihistamines, might warrant clinical trials as COVID-19

treatments.



• To further promote this drug-repurposing approach, researchers in China have created a

publicly accessible web server to explore potential COVID-19 treatments using

proteomics.

• Stakeholders reviewing this topic thought proteomics and protein mapping was a

promising approach to assess the repurposing of existing drugs that might dramatically

shorten the timeline for clinical testing and making new COVID-19 treatments available

to patients.

• Stakeholders also anticipated a large, continuing need for new COVID-19 treatments

because of the high vaccine refusal rates and the emergence of new treatment-resistant

coronavirus variants.

Description

Researchers at the University of California, San Francisco, have developed a protein

interaction map for SARS-CoV-2.155 The map might facilitate the repurposing of drugs approved

or in development for other indications to treat COVID-19. The team identified 66 druggable

human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in

clinical trials, and 28 preclinical compounds). The team then tested a subset of these compounds

for their activity against SARS-CoV-2 in the laboratory. Researchers identified 2 drug classes

with antiviral activity: messenger RNA translation inhibitors (including the investigational

cancer drugs zotatifin and ternatin-4) and predicted regulators of the sigma1 and sigma2

receptors (including the hormone progesterone, antipsychotic drugs haloperidol and

chlorpromazine, the antianxiety drug siramesine, and the antihistamines clemastine and

cloperastine). Researchers suggest these agents could result in new therapeutic approaches to

treat COVID-19 that warrant further testing, leading to clinical trials.155,156

In related work, Chinese Academy of Sciences researchers have created a publicly available

web server to explore potential COVID-19 treatments. The web server has 2 goals: to predict

protein targets for drugs or compounds observed in clinical or laboratory studies and to identify

lead compounds against potential drug targets via molecular docking.157 Further, University of

Virginia (Charlottesville) researchers proposed a computational model to predict protein

interactions between novel viruses and humans using only protein sequence information,

dramatically shortening the discovery process compared with conventional techniques.158





Identifying drugs approved for other indications that might also treat coronavirus could speed

the development of new COVID-19 treatments and benefit patients sooner. Screening existing

drugs for potential benefit against COVID-19 might also reduce drug development costs for the

new indications. Further, the protein interaction maps could expand the potential treatment

targets for new therapeutic agents in development for other indications.



Between June 5, 2020, and April 19, 2021, seven ECRI stakeholders—reflecting physician,

research, health systems, and health care generalist perspectives—provided comments and

ratings on this topic. The list below summarizes key stakeholder perspectives.

• The protein mapping approach could help shorten drug development time by years, by

identifying which existing drugs have clinically important effects on COVID-19 and

warrant further clinical testing. The proteomics approach might also help identify

compounds that could work in combination against COVID-19.

• Proteomics is well suited to help researchers learn how to neutralize viruses, because

viruses basically consist of DNA or RNA enclosed in a protein outer shell.

• Shortening the development pipeline by using available drugs with established safety

profiles could ultimately improve patient outcomes by making more treatment options

available sooner and to more patients globally.

• Repurposing approved drugs to treat COVID-19 could help alleviate supply issues that

can sometimes affect new investigational treatments.

• High rates of vaccine refusal combined with new and future coronavirus variants that are

resistant to available treatments will increase the importance of and need for rapid

discovery and testing of effective new COVID-19 therapeutics.

TD-0903 for Treating Acute Lung Injury in COVID-19


Stakeholders reviewing this topic thought that TD-

0903 for treating acute lung injury in COVID-19

could have a moderately high impact on patient-



Highlights

• TD-0903 is an inhaled janus kinase (JAK) inhibitor being investigated as a treatment for

patients with acute lung injury in COVID-19 to prevent disease progression to acute

respiratory distress syndrome (ARDS).

• Compared with placebo, initial reported phase 2 clinical data suggest numerical

improvements in several clinical outcomes in patients treated with TD-0903.

• Stakeholders commenting on this topic thought TD-0903 has potential to improve patient

outcomes and improve survival in patients with severe COVID-19 with lung

inflammation.

• Stakeholders also thought it might lead to health care cost savings from reduced

hospitalizations, intensive care resource usage, and health complications, even though it

is likely to be used in combination with other COVID-19 therapies, thus increasing up-

front treatment costs.



Description

TD-0903 (Theravance Biopharma, Dublin, Ireland) is an investigational, inhaled JAK

inhibitor intended to treat COVID-19 by preventing the progression of acute lung injury to life-

threatening ARDS. ARDS in COVID-19 is thought to be caused, in part, by a rapid influx of

inflammatory proteins called cytokines into the lungs (ie, cytokine storm). Excessive release of

proinflammatory cytokines is thought to lead to hyperinflammation in COVID-19 and correlate

with severe disease and poor outcomes.136 Intervening early to block cytokine storm in COVID-

19 pneumonia might be critical for survival.159 TD-0903 purportedly broadly inhibits the activity

of JAKs that play a central role in cytokine signaling.160 It is taken in a nebulized form to

directly target hyperinflammation in the lungs and limit systemic suppression of the immune

system.

A phase 2 study enrolling 222 hospitalized COVID-19 patients is ongoing. Primary

completion is expected in April 2021.161 In February 2021, Theravance Biopharma reported

initial clinical data from part 1 of the trial. The developer reported TD-0903 was generally well

tolerated, was related to no serious adverse events, and demonstrated numerical improvements in

outcomes, including all-cause mortality by day 28 of hospitalization, clinical status worsened

during the 7-day treatment period, survival with no respiratory failure on day 28, and average

time to hospital discharge. Data from part 2 of the trial are anticipated in the second quarter of

2021.162







TD-0903 to treat acute lung injury in COVID-19 might improve patient outcomes by

preventing disease progression to ARDS, thus potentially preventing disease complications or

death. Preventing ARDS is likely to shorten length of hospitalization and reduce intensive care

resource use (eg, mechanical ventilation), thus reducing the burden on the health care system and

potentially resulting in health care cost savings related to hospitalization and intensive care

resources. Population health outcomes might improve as a result of improved individual patient

outcomes and reduced burden on local health care systems.


Between June 1, 2020, and April 19, 2021, six ECRI stakeholders, reflecting health systems,

nursing, physician, and research perspectives, provided comments and ratings on this topic. The

list below provides a summary of key stakeholder perspectives.

• TD-0903 to treat acute lung injury in COVID-19 might significantly improve patient

outcomes and reduce mortality in patients who have severe COVID-19 with lung

inflammation.


• TD-0903’s route of administration (ie, inhalation) is promising since it targets the lungs

directly, and it might be easier to use in the acute care setting.

• TD-0903 might increase treatment cost since it is likely to be used in combination with

other drug therapies, but its cost might be offset by health care cost savings from reduced

intensive care hospital stays, mechanical ventilation, and health complications.

• If efficacious, it might change the health care delivery process by reducing the need for

mechanical ventilation for severe COVID-19 treatment.


Chapter 6. Vaccines and Prophylaxis

Chapter Summary


vaccine and prophylaxis topics. Eight of these topics are listed in the January 2021 PCORI


Volume 2, Issue 1; the remaining 2 topics were added to the system subsequent to that report. All

10 topics were sent for comment to internal ECRI stakeholders, and each received at least 5 sets

of ratings and comments from stakeholders between May 18, 2020, and March 11, 2021.

Additional ratings and comments might also have been received after March 11, 2021.

One topic included in the previous High Impact Report, AZD1222 (ChAdOx1 nCoV-19)

vaccine for preventing coronavirus infection, was excluded from this report after stakeholders re-

reviewed the topic and rated it as having only moderate potential for impact.

From among the 10 topics, 8 topics have been selected that internal ECRI stakeholders

thought have moderately high to high impact potential relative to COVID-19-related patient-

oriented health care in the United States within the next 12 months.



received, on average, high impact ratings and demonstrated considerable consensus among

stakeholders. Topics are arranged first in descending order by potential impact score; topics with

the same score are listed alphabetically by topic title.

Table 6.1. Included Vaccine and Prophylaxis Topics


Moderna COVID-19 vaccine for preventing coronavirus infection 3.8

Novavax COVID-19 vaccine (NVX-CoV2373) for preventing SARS-CoV-2 infectiona 3.7

Variant-specific vaccines for preventing COVID-19a 3.7

ARCT-021 (LUNAR-COV19) vaccine for preventing SARS-CoV-2 infection 3.6

JNJ-78436735 (Ad26.COV2-S) vaccine for preventing coronavirus infection 3.4

Pfizer-BioNTech COVID-19 vaccine for preventing coronavirus infection 3.4

Sanofi-GSK SARS-CoV-2 vaccine for preventing SARS-CoV-2 infectiona 3.4

CoVLP vaccine for preventing SARS-CoV-2 infectiona 3.2

a Topic appears for the first time in this High Impact Report.


Table 6.2 lists 2 topics considered, but not selected, for inclusion in this High Impact Report.

Excluded topics received, on average, low to moderate impact ratings and were not considered

by most stakeholder reviewers to have high impact potential. Topics are arranged first in

descending order by potential impact score and second in ascending order alphabetically by topic

title.

Table 6.2. Vaccine and Prophylaxis Topics Considered but Not Included


AZD1222 (ChAdOx1 nCoV-19) vaccine for preventing SARS-CoV-2 infection 3.0

Monoclonal antibodies targeting coronavirus spike protein receptor binding domain

for preventing COVID-19a

2.8

Topic Summaries

We present below 8 summaries on topics deemed to have high impact potential. Topics are

arranged first in descending order by potential impact score; topics with the same score are listed


Moderna COVID-19 Vaccine for Preventing Coronavirus Infection


Stakeholders reviewing this topic thought that the

Moderna COVID-19 vaccine (mRNA-1273) for

preventing coronavirus infection could have a


relative to COVID-19 in the United States within

the next 12 months.

Highlights

• The Moderna vaccine is an investigational vaccine intended to generate a protective

immune response against the coronavirus spike protein expressed on the surface of the

virus.

• The Moderna vaccine is in phase 3 development, with primary completion expected in

October 2022.

• FDA granted the Moderna vaccine Emergency Use Authorization (EUA) for preventing

COVID-19 in individuals aged 18 years and older.

• Stakeholders commenting on this topic thought that the Moderna vaccine was safe and

effective, with widespread immunization efforts pushing population health toward

achieving herd immunity; however, there is concern over the vaccine’s ability to create

an effective immune response against emerging variants.



Description

The Moderna vaccine (Moderna, Cambridge, Massachusetts) is a vaccine against coronavirus

that uses messenger RNA (mRNA) to encode the viral spike protein expressed on the surface of

the virus.163 The vaccine purportedly enters host antigen-presenting cells and induces expression

of the viral spike protein, which acts to elicit a host immune response against the virus to prevent

future infection.

Published primary efficacy data from the phase 3 randomized trial found that the Moderna

vaccine had an efficacy of 94.1%. Of the 196 confirmed cases of COVID-19 included in the

analysis, 185 cases were observed in the placebo group vs 11 cases observed in the vaccine

group, resulting in a point estimate of vaccine efficacy of 94.1%. There were 30 severe cases of

COVID-19, all of which occurred in the placebo group, leading to a point estimate of vaccine

efficacy of 100% against severe COVID-19.164

Initial studies of the vaccine’s efficacy against SARS-CoV-2 variants of concern, compared

with prior variants, found no significant impact on neutralization of B.1.1.7, first identified in the

United Kingdom. However, a 6-fold, but still significant, decrease was observed in neutralization

of B.1.351, first identified in South Africa, compared with prior variants.165

On December 18, 2020, FDA granted the Moderna COVID-19 vaccine EUA for preventing

COVID-19 in individuals aged 18 years and older.166 A phase 3 trial in 30 000 individuals is in

progress, with full data expected by October 2022.167 The vaccine is part of the US government’s

Operation Warp Speed. The company purportedly remains on track to be able to deliver

approximately 500 million doses per year beginning in 2021.168

Moderna has agreed to set the preorder price of the Moderna vaccine between $32 and $37

per dose for small quantities of the vaccine.169




• Clinicians and/or caregiver safety





In ongoing trials, the Moderna vaccine has proven effective against SARS-CoV-2. It might

improve patient outcomes as well as clinician or caregiver safety by preventing or mitigating

adverse health events caused by infection. It might also aid the development of herd immunity

among vulnerable populations, thereby decreasing negative COVID-19-related outcomes and

improving individual and population health outcomes over time. It might also help decrease the

overall cost burden to governments and the health care system. An effective vaccine against

coronavirus could also enable more relaxed social-distancing protocols.

Although most expected outcomes from an effective vaccine are positive, a vaccine shortage

could lead to increased disparities if certain populations are unable to access the vaccine.


Facilities that administer vaccines (eg, hospitals, clinics, pharmacies) might experience a

transient increase in patient volume as people seek vaccinations. In addition, currently unknown

adverse events might come to light if the vaccine is brought to market prematurely (ie, before

full safety data are available). Considering that adverse events resembling coronavirus-like

symptoms (chills, fatigue, headache, and myalgia) occurred in more than half the study

participants, a proactive information campaign regarding the benefits of immunization might be

necessary to minimize vaccine hesitancy and concerns.170,171


Between February 25, 2021, and March 2, 2021, five ECRI stakeholders—reflecting health

systems and research perspectives—provided comments and ratings on this topic. The list below

summarizes key stakeholder perspectives.

• The Moderna vaccine might substantially improve patient and population health

outcomes by preventing coronavirus infection or reducing case severity in some patients.

• The emergence of new variant strains of COVID-19 might result in lower efficacy as well

as the need for a booster or modified vaccine; however, specific vaccines against these

variants might be able to be developed in a few months due to the advancements and

funding put into RNA technology.

• Availability of the Moderna vaccine might help relax social-distancing guidelines and

economic disruptions, which could result in an improvement in overall population

psychological health.

• While analysis of the phase 3 trial said that the vaccine was safe, the long-term safety

profile is yet to be completely determined; additional adverse events are being reported in

the general population vaccinated after the vaccine was authorized.

• Since the Moderna vaccine does not require extreme refrigeration, the vaccine might be

more accessible in rural and underserved areas than other authorized COVID-19

vaccines, allowing for improved access and reduced disparities.

Novavax COVID-19 Vaccine (NVX-CoV2373) for Preventing

Coronavirus Infection



Novavax COVID-19 vaccine (NVX-CoV2373)

could have a high impact on patient-oriented



Highlights

• The Novavax vaccine is an investigational vaccine intended to generate a protective

immune response against coronavirus by mimicking the structure of the coronavirus

spike protein expressed on the surface of the virus.



• The Novavax vaccine is in phase 3 development, with primary completion expected in

March 2021.

• Novavax has begun a rolling review of NVX-CoV2373 with FDA for Emergency Use

Authorization (EUA).

• Stakeholders commenting on this topic thought that NVX-CoV2373’s efficacy data are

promising, especially against B.1.1.7, the COVID-19 variant first identified in the United

Kingdom, but there is concern regarding the vaccine’s ability to generate an immune

response that is protective against other emerging variants such as B.1.351, a variant first

identified in South Africa.

Description

The Novavax vaccine (Gaithersburg, Maryland) is a vaccine against coronavirus that uses

recombinant nanoparticles that mimic the structure of a full-length SARS-CoV-2 spike protein,

the protein expressed on the surface of the virus that is responsible for viral fusion and entry.

Immune cells in the body react to the spike nanoparticles, resulting in a host immune response

against the virus to prevent future infection. The vaccine is coadministered with Novavax’s

Matrix-M1 adjuvant to help enhance the immune response.172

Primary efficacy data of a phase 3 randomized trial involving 15 000 adults in the United

Kingdom, announced through a company press release, found that the Novavax vaccine had an

efficacy of 96.4% against the original strain of the virus and 86.3% against the B.1.1.7 variant,

first identified in the United Kingdom. Phase 2 efficacy results from the South Africa trial, where

a majority of the COVID-19 strains were the B.1.351 variant (first identified in South Africa),

found vaccine efficacy to be 55.4% among 2665 HIV-negative participants. The vaccine has an

overall efficacy of 100% against severe disease.173

NVX-CoV2373 is currently in a phase 3, randomized trial in the United States that is

enrolling 30 000 participants, with primary completion expected in March 2021.174 The vaccine

is part of the US government’s Operation Warp Speed, and the manufacturer announced plans to

produce up to 150 million doses per month globally by the third quarter of 2021.175,176 Novavax

has begun a rolling review process with FDA for EUA of NVX-CoV2373.177




• Clinicians and/or caregiver safety





If the Novavax vaccine is proved effective against coronavirus, it might improve patient

outcomes as well as clinician or caregiver safety by preventing or mitigating adverse health

events caused by infection. It might also aid the development of herd immunity among


vulnerable populations, thereby decreasing negative COVID-19-related outcomes and improving

individual and population health outcomes over time. It might also help decrease the overall cost

burden to governments and the health care system. An effective vaccine against coronavirus

could also enable more relaxed social-distancing protocols.






full safety data are available).


Between February 2, 2021, and February 26, 2021, six ECRI stakeholders, reflecting health

systems, physician, and research perspectives, provided comments and ratings on this topic. The

list below provides a summary of key stakeholder perspectives.

• NVX-CoV2373 might substantially improve patient and population health outcomes by

preventing coronavirus infection or reducing case severity in some patients.

• The Novavax vaccine’s use of nanoparticles adds a different approach to immunization

than the authorized messenger RNA (mRNA) vaccines, which might help patients who

are unable to develop immune responses from certain vaccine platforms.

• If NVX-CoV2373 is authorized, the availability of another vaccine against COVID-19

might help ease the current production and distribution bottlenecks, pushing society

toward achieving herd immunity and ending the pandemic.

• The Novavax vaccine’s high efficacy against the rapidly spreading COVID-19 UK

variant is promising, but there is concern over the vaccine’s effectiveness against the

South African and other emerging variants.

• Since the Novavax vaccine is not limited by the need for cold chain infrastructure, the

vaccine might be more accessible in rural and underserved areas than other authorized

COVID-19 vaccines, allowing for improved access and reduced disparities. However, the

2-dose regimen required by this vaccine might limit widespread use in rural and hard-to-

access areas compared with a single-dose option.

Variant-Specific Vaccines for Preventing COVID-19



variant-specific vaccines for preventing COVID-

19 could have a high impact on patient-oriented





Highlights

• Variant-specific vaccines are investigational vaccines intended to generate a protective

immune response against emerging coronavirus variants that may render current COVID-

19 vaccines ineffective.

• The variant-specific vaccines are in phase 1/2 development, with primary completion of

mRNA-1273.351 expected in August 2022.

• Variant-specific vaccines might be used to immunize individuals who have not received

any COVID-19 vaccine or be used as booster shots after vaccination with currently

authorized COVID-19 vaccines.

• Stakeholders commenting on this topic thought that variant-specific vaccines, if effective,

might be able to able to control emerging variants quickly, thereby preventing spikes in

transmission, hospitalization, and death rates caused by the disease; however, there was

concern that these vaccines might increase health disparities due to lack of timely vaccine

delivery in underserved and rural populations.

Description

Mutations in viruses are inevitable, leading to viral variants that can emerge and persist

around the world. These variants can result in faster spread and increased transmission, helping

the disease persist in the population. Due to the emergence of certain SARS-CoV-2 variants,

vaccines specific to these variants might be necessary to protect individuals from contracting

COVID-19.

Of particular concern are variants harboring mutations in the SARS-CoV-2 spike protein,

which the virus uses to attach itself to the surface of human cells and gain entry.178 Since the S

protein is the target of many of the currently available COVID-19 vaccines, changes to this

protein may affect the efficacy of these vaccines.179 Initial studies have found that the mRNA-

1273 vaccine has a 6-fold reduced neutralization against the B.1.351 variant, first identified in

South Africa.165 Neutralization of B.1.351 by BNT162b2 was reduced by two-thirds when

compared with early COVID-19 isolates.180

Moderna, the developer of mRNA-1273, has announced a phase 1 trial in 210 participants to

determine the neutralizing ability of a vaccine (mRNA-1273.351) specific for B.1.351.181

Moderna has also amended its phase 2 study of mRNA-1273 to give 60 participants previously

vaccinated with mRNA-1273 a single booster dose of either mRNA-1273.351 or a multivalent

booster candidate, mRNA-1273.111.182 Pfizer and BioNTech, the developers of BNT162b2, are

discussing the start of a study using a messenger RNA (mRNA) vaccine with a variant sequence,

which would lead to an adaptable vaccine for use against B.1.351 or other emerging variants.183











If the variant-specific vaccines are proved effective against emerging coronavirus variants,

they might improve patient outcomes as well as clinician or caregiver safety by preventing or

mitigating adverse health events caused by infection. They might also aid the development of

herd immunity among vulnerable populations, thereby decreasing negative COVID-19-related

outcomes and improving individual and population health outcomes over time. They might also

help decrease the overall cost burden to governments and the health care system. Effective

vaccines against current and emerging variants of coronavirus could also enable more relaxed

social-distancing protocols.

Although most expected outcomes from effective variant-specific vaccines are positive, a

vaccine shortage could lead to increased disparities if certain populations are unable to access the

vaccines. Facilities that administer vaccines (eg, hospitals, clinics, pharmacies) might experience

a transient increase in patient volume as people seek vaccinations. In addition, currently

unknown adverse events might come to light if the vaccines are brought to market prematurely

(ie, before full safety data are available). Misinformation about vaccines might result in the need

for proactive information campaigns highlighting the benefit of immunizations against COVID-

19 variants to minimize vaccine hesitancy in the public.


Between March 1, 2021, and March 9, 2021, six ECRI stakeholders, reflecting health

systems and research perspectives, provided comments and ratings on this topic. The list below

provides a summary of key stakeholder perspectives.

• Variant-specific vaccines might substantially improve patient and population health

outcomes by preventing coronavirus infection or reducing case severity in some patients,

especially if authorized vaccines are unable to effectively protect individuals and slow

infection.

• Public misinformation over the variant strains’ ability to escape the vaccine’s protection

and antivaccination campaigns, as well as mistakes in initial vaccine rollout, might affect

compliance of variant-specific vaccine programs.

• Since vaccine platforms that use RNA technology are new, RNA variant-specific

vaccines might cause long-term safety concerns and adverse effects by exposing

recipients to multiple doses of lipid nanoparticles.

• Variant-specific vaccines might be able to address new pathogenic variants quickly to

control transmission before the variant virus begins to spread; however, the distribution

of new variant-specific vaccines might increase health disparities for individuals living in

rural or underserved areas if they are not able to constantly obtain new or updated

vaccines.


ARCT-021 (LUNAR-COV19) Vaccine for Preventing SARS-CoV-2

Infection



that the ARCT-021 (LUNAR-COV19)

vaccine for preventing SARS-CoV-2

infection could have a moderately high to




Highlights

• ARCT-021 is a messenger RNA (mRNA) vaccine intended to generate a protective

immune response against the coronavirus spike protein expressed on the surface of the

virus.

• ARCT-021 is under study in a randomized phase 2 trial, and the developer intends to

initiate a phase 3 trial in the first half of 2021.

• Based on the low dose of vaccine required to induce immune responses, the manufacturer

claims that only a single dose might be needed for protection and plans to be able to

produce hundreds of millions of doses in 2021, if authorized by FDA.

• Stakeholders commenting on this topic thought that, if effective, ARCT-021 could

improve patient and population health while also decreasing health care disparities due to

low doses of the vaccine being easily mass produced; however, more clinical data on its

safety and efficacy are needed.

Description

ARCT-021 (Arcturus Therapeutics, San Diego, California) is a lipid nanoparticle–

encapsulated mRNA vaccine that encodes a full-length viral spike protein responsible for host

receptor binding and cellular entry.184 The vaccine purportedly enters host antigen-presenting

cells and induces expression of the viral spike protein, which elicits a host immune response that

prevents future coronavirus infection. The mRNA component of the vaccine is self-amplifying,

which purportedly increases immunogenicity. Additionally, the manufacturer has produced a

lyophilized (ie, freeze-dried) version of the vaccine that would purportedly reduce cold chain

storage requirements compared with existing mRNA vaccines that are shipped as a frozen

liquid.185

Preliminary immunogenicity data from a randomized phase 1/2 study in 106 participants

given either 1 or 2 doses of ARCT-021 (1-10 μg per injection) or placebo showed that

participants receiving doses in the range of 5 to 7.5 μg achieved neutralizing antibodies at the

low end of the range of levels found in serum from patients who recovered from COVID-

19.186,187 Participants also developed T-cell responses against the spike protein and receptor

binding domain. The vaccine had a favorable safety and tolerability profile in participants and

resulted in no moderate or severe fevers.



ARCT-021 is in phase 2 development in a 600-patient trial in the United States and

Singapore.188 The manufacturer has announced that it expects to initiate a phase 3 trial of the

vaccine using both single-shot and prime-boost (ie, 2-shot) dosing strategies in the first half of

2021.189 Pending regulatory authorization, the manufacturer plans to be able to produce hundreds

of millions of doses before the end of 2022.185









If ARCT-021 is proved effective against coronavirus, it might improve patient outcomes as

well as clinician or caregiver safety by preventing or mitigating adverse health events caused by

infection. It might also aid the development of herd immunity in vulnerable populations, thereby

decreasing negative COVID-19-related outcomes and improving individual and population

health outcomes over time. If effective after a single dose, the vaccine might confer protection

quicker and easier and aid patients with limited access to care. It might also help decrease the

overall cost burden to governments and the health care system for implementation of a

vaccination program. An effective vaccine against coronavirus could also enable more relaxed

social-distancing protocols.

Although most potential impacts of an effective vaccine are positive, a vaccine shortage







Between August 31, 2020, and April 19, 2021, six ECRI stakeholders—reflecting health care

generalist, health systems, nursing, physician, and research perspectives—provided comments

and ratings on this topic. The list below summarizes key stakeholder perspectives.

• ARCT-021 might substantially improve patient and population health outcomes by

preventing coronavirus infection; however, more safety and efficacy data are needed to

determine if the vaccine is adequate and effective at a low dose.

• A low-dose vaccine might allow for mass production, which could prevent health care

disparities if underserved communities and at-risk populations are given ARCT-021 at no

cost.


• Availability of an additional coronavirus vaccine might be significant in alleviating

vaccine shortages and in halting or slowing down the coronavirus pandemic.

• An accelerated development timeline of ARCT-021 might result in data that do not

accurately determine the extent of long-term immunity conferred by the vaccine.

• If the vaccine efficacy and safety profile of ARCT-021 is favorable, it might aid in

decreasing public vaccine hesitancy surrounding adverse events experienced with other

COVID-19 vaccines.

JNJ-78436735 (Ad26.COV2-S) Vaccine for Preventing Coronavirus

Infection



the JNJ-78436735 vaccine for preventing

coronavirus infection could have a moderately




Highlights

• JNJ-78436735 is an investigational vaccine intended to generate a protective immune

response against the coronavirus spike protein expressed on the surface of the virus.

• JNJ-78436735 is in phase 3 development, with full data expected in March 2023.

• The manufacturer hopes to produce and distribute up to 1 billion doses of the vaccine

globally beginning in 2021.

• Stakeholders commenting on this topic thought that because JNJ-78436735 was

developed using a traditional vaccine platform, it might provide a more familiar

alternative for individuals hesitant to receive COVID-19 vaccines developed through

novel mechanisms.

• Although JNJ-78436735 is an effective COVID-19 vaccine, stakeholders were concerned

regarding its ability to effectively protect against newly emerging COVID-19 variants.

Description

JNJ-78436735 (Ad26.COV2-S; Johnson & Johnson, New Brunswick, New Jersey) is a

recombinant (ie, genetically engineered) adenoviral vector vaccine against coronavirus. JNJ-

78436735 uses a shortened, weakened form of a common cold virus to carry genetic material

into special antigen-presenting cells in the patient’s body, where the genetic material induces the

production of the viral spike protein normally found on the surface of the coronavirus. The spike

protein then moves to the cell’s surface, where it stimulates an immune response intended to

prevent future infection by coronavirus.190

Topline efficacy and safety data from the randomized phase 3 ENSEMBLE trial, announced

through a company press release, found that JNJ-78436735 was 66% effective at preventing



moderate to severe disease and 85% effective at preventing severe disease 28 days after a single

dose of vaccine, with no significant safety concerns. Efficacy in preventing moderate to severe

disease across geographic regions was 72% in the United States, 66% in Latin America, and 57%

in South Africa.191 A 2-dose protocol is also being studied in the phase 3 ENSEMBLE 2 trial,

with primary completion expected in May 2022.192

On February 27, 2021, FDA granted the Johnson & Johnson COVID-19 vaccine Emergency

Use Authorization for preventing COVID-19 in individuals aged 18 years and older.193 JNJ-

78436735 is in a large phase 3 trial in 40 000 people.194 Full 12-month results on its safety and

effectiveness against coronavirus are not expected until March 2023.195 Effective April 23, 2021,

the CDC and FDA recommended that the use of the vaccine resume in the United States.

However, the agencies warn that women with low platelets younger than 50 years especially

should be aware of the rare risk of blood clots after vaccination. The US government has agreed

to purchase 100 million doses for about $10 per dose.196 The company plans to manufacture 100

million doses for the United States by end of June 2021.193









If JNJ-78436735 is proved effective against coronavirus, it might improve patient outcomes

as well as clinician or caregiver safety by preventing or mitigating adverse health events caused

by infection. It might also aid the development of herd immunity among vulnerable populations,

thereby decreasing negative COVID-19-related outcomes and improving individual and

population health outcomes over time. It might also help decrease the overall cost burden to

governments and the health care system. An effective vaccine against coronavirus could also

enable more relaxed social-distancing protocols.








Between June 25, 2020, and July 6, 2020, five ECRI stakeholders—reflecting research,

nursing, and systems perspectives—provided comments and ratings on this topic. The list below

summarizes key stakeholder perspectives.

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html


• ARCT-021 might substantially improve patient and population health outcomes by

preventing coronavirus infection; however, more safety and efficacy data are needed to

determine if the vaccine is adequate and effective at a low dose.

• A low-dose vaccine might allow for mass production, which could prevent health care

disparities if underserved communities and at-risk populations are given ARCT-021 at no

cost.

• Availability of a coronavirus vaccine might be significant in halting or slowing down the

coronavirus pandemic.

• An accelerated development timeline of ARCT-021 might result in data that do not

accurately determine the extent of long-term immunity conferred by the vaccine.

Pfizer-BioNTech COVID-19 Vaccine for Preventing Coronavirus

Infection



the Pfizer-BioNTech COVID-19 vaccine

(BNT162b2) for preventing coronavirus

infection could have a moderately high impact



12 months.

Highlights

• The Pfizer-BioNTech vaccine is a messenger RNA (mRNA) vaccine intended to generate

a protective immune response against the coronavirus spike protein expressed on the

surface of the virus.

• The Pfizer-BioNTech vaccine is in phase 2/3 development, with primary completion

expected on August 3, 2021.

• FDA granted the Pfizer-BioNTech vaccine Emergency Use Authorization (EUA) for

preventing COVID-19 in individuals aged 16 years and older.

• Stakeholders commenting on this topic thought that early data on the vaccine platform’s

safety and ability to simulate an immune response were promising; however, the

effectiveness and immune response duration of the mRNA vaccine against COVID-19

and emerging variants must continue to be evaluated in clinical trials.

Description

The Pfizer-BioNTech vaccine (Pfizer, New York, New York, and BioNTech, Cambridge,

Massachusetts) is a lipid nanoparticle–encapsulated mRNA vaccine that encodes the entire viral

spike protein responsible for receptor binding and cellular entry.197,198 The vaccine purportedly

enters host antigen-presenting cells and induces expression of the viral spike protein, which acts

to elicit a host immune response against the virus to prevent future infection.



Primary safety and efficacy analysis of the phase 2/3 trial stated that the Pfizer-BioNTech

vaccine was found to be 95% effective in preventing COVID-19 in participants without evidence

of prior infection.199 The data also reported that the vaccine was well tolerated across all

populations, with the most common adverse events being fatigue and headache, experienced at a

frequency of 3.8% and 2%, respectively. FDA granted the Pfizer-BioNTech vaccine EUA on

December 11, 2020, for preventing COVID-19 in individuals aged 16 years and older.200

A retrospective cohort study from Israel of 596 618 vaccinated people found that estimated

vaccine efficacy against documented infection at days 14 through 20 after the first dose or at 7 or

more days after the second dose was 46% and 92%, respectively.201 Initial studies of the

vaccine’s efficacy against SARS-CoV-2 variants of concern demonstrated a 3-fold decrease in

neutralization of B.1.351, a variant first identified in South Africa, compared with earlier

variants.202

The Pfizer-BioNTech vaccine is also in a large phase 2/3 trial in more than 43 000 people.

Full results on its safety and effectiveness against coronavirus are not expected until August

2021.203 Under an agreement as part of Operation Warp Speed, the US government has

purchased 300 million doses.204









In ongoing trials, the Pfizer-BioNTech vaccine has proven effective against SARS-CoV-2. It

might improve patient outcomes as well as clinician or caregiver safety by preventing or

mitigating adverse health events caused by infection. It might also aid the development of herd

immunity among vulnerable populations, thereby decreasing negative COVID-19-related

outcomes and improving individual and population health outcomes over time. It might also help

decrease the overall cost burden to governments and the health care system. An effective vaccine

against coronavirus could also enable more relaxed social-distancing protocols.






full safety data are available). Considering that adverse events resembling coronavirus-like

symptoms (chills, fatigue, and headache) occurred in more than half of the study participants, a

proactive information campaign regarding the benefits of immunization might be necessary to

minimize vaccine hesitancy and concerns.170,198



Between February 25, 2021, and March 8, 2021, five ECRI stakeholders—reflecting health

care generalist, health systems, and research perspectives—provided comments and ratings on

this topic. The list below summarizes key stakeholder perspectives.

• The Pfizer-BioNTech vaccine might significantly improve patient and population health

outcomes by preventing infection with coronavirus, mitigating disease spread, and

conferring immunity to much of the population; however, more information is needed

regarding the duration of immunogenicity as well as the vaccine’s ability to protect

against emerging variants.

• Boosters or new formulations of the Pfizer-BioNTech vaccine might need to be made to

protect against virus variants, and large-scale immunization efforts would be necessary to

prevent further outbreaks.

• The accelerated development timeline for the Pfizer-BioNTech vaccine might pose

unforeseen safety and efficacy risks when manufacturing and distributing the vaccine.

• The Pfizer-BioNTech vaccine’s temperature storage requirements might have contributed

to health disparities in areas where the vaccine could not be easily stored and

administered. However, the company has recently validated the vaccine in storage

conditions that would make the vaccine more available at a community-wide level.

Sanofi-GSK SARS-CoV-2 Vaccine for Preventing SARS-CoV-2 Infection



the Sanofi-GSK SARS-CoV-2 vaccine for

preventing SARS-CoV-2 infection could have a




Highlights

• The Sanofi-GSK SARS-CoV-2 vaccine uses a recombinant version of the SARS-CoV-2

spike protein to generate a protective immune response against COVID-19.

• The Sanofi-GSK SARS-CoV-2 vaccine does not have the same deep-cold storage

requirements of some other COVID-19 vaccines, potentially easing distribution

challenges.

• A vaccine formulation error in early trials caused a lower than desired immune response

in older adults, slowing vaccine development and delaying possible US regulatory

authorization until at least late 2021.

• Stakeholders commenting on this topic thought that, if safe and effective, the Sanofi-GSK

SARS-CoV-2 vaccine could reduce disparities and help improve access to vaccinations in

underserved populations domestically and globally because it has less burdensome cold-

storage requirements than other available COVID-19 vaccines.



Description

GlaxoSmithKline (GSK) plc (Brentford, United Kingdom) and Sanofi (Paris, France) are

jointly developing an adjuvanted, recombinant protein–based vaccine that is intended to generate

a protective immune response against SARS-CoV-2.205 The Sanofi-GSK SARS-CoV-2 vaccine

consists of a recombinant SARS-CoV-2 spike protein, which is expressed on the surface of

SARS-CoV-2 and is responsible for viral fusion and entry.206 The vaccine is expected to engage

the immune system in a manner similar to that of other recombinant protein vaccines (eg,

hepatitis B vaccine, human papillomavirus vaccine).207 The recombinant protein vaccine is

formulated with an adjuvant intended to boost the immune response to the vaccine, thereby

requiring less antigen to stimulate a response. Using less antigen per dose potentially allows

more total vaccine doses to be produced in less time.205,206 In clinical trials, the vaccine is given

as 2 injections spaced 21 days apart.208

The vaccine is part of the US government’s Operation Warp Speed and is in a phase 1/2

randomized trial in 440 adults with estimated completion in November 2021.209 Due to

inadequate results in older adults caused by a vaccine formulation error in the phase 1/2 trial, the

company has pushed back its target date of a request for regulatory authorization to the second

half of 2021.208 Unlike vaccines further in development that are based on messenger RNA

(mRNA) platforms and need to be kept frozen before use, the Sanofi-GSK vaccine is intended to

be stable in liquid form at refrigerator temperatures.206,210









The Sanofi-GSK SARS-CoV-2 vaccine might reduce the general risk of coronavirus

infection and lessen the need for social distancing if it is authorized for clinical use. If safe and

effective at reducing infections, the vaccine could improve patient outcomes and reduce costs for

treating severe COVID-19 infections. Distributing the Sanofi-GSK vaccine might be easier and

less costly since the vaccine can be stored at normal refrigerator temperatures, thus lowering the

cold chain burden for vaccine providers. As with other vaccines during the pandemic, limited

production capacity of the Sanofi-GSK vaccine might result in vaccine shortages, depending on

its demonstrated level of effectiveness and market demand. However, the accelerated approval

process might mean that the vaccine does not achieve the desired level of protection against

COVID-19. Further, rapid approval also raises concerns that unexpected or undetected adverse

events related to the vaccine could arise after the vaccine reaches widespread use.



Between November 20, 2020, and January 20, 2021, five ECRI stakeholders, reflecting

physician, nursing, research, and health systems perspectives, provided comments and ratings on

this topic. The list below provides a summary of key stakeholder perspectives.

• A COVID-19 vaccine that does not have the deep-cold storage requirements of some

other COVID-19 vaccines could improve vaccine access to underserved populations

domestically and globally.

• If safe and effective at preventing COVID-19, another vaccine option might help

overcome global shortages, potentially reducing disparities. Broad access to and

acceptance of vaccination globally could speed economic recovery, possibly restoring

employment opportunities in hard-hit industrial sectors.

• Proposed proof-of-vaccination requirements for travel or large gatherings could

encourage more individuals to seek COVID-19 vaccinations. The availability of more

vaccine options could make such vaccination requirements somewhat less burdensome.

Large-scale vaccination programs could be very costly to implement. However, the benefits

of a healthy population and economy unhindered by pandemic fears could offset the costs of

widespread vaccinations.

CoVLP Vaccine for Preventing SARS-CoV-2 Infection



Coronavirus Virus-Like Particle (CoVLP) vaccine

for preventing SARS-CoV-2 infection could have a

moderately high impact on patient-oriented health

care relative to COVID-19 in the United States


Highlights

• The CoVLP vaccine is designed to mimic the shape of the SARS-CoV-2 virus to

stimulate an immune system response without using infectious genetic material from the

virus.

• The 2-dose CoVLP vaccine is in phase 2/3 trials scheduled for completion in December

2021, and it has FDA Fast Track designation.

• Results of a phase 1 trial suggested patients vaccinated with CoVLP vaccine showed

neutralizing antibody responses up to 50 times higher than those seen in individuals who

had recovered from COVID-19 infection.

• Stakeholders commenting on this topic thought that if safe and effective at reducing

COVID-19, the CoVLP vaccine could be an important addition to expand global

vaccination programs, helping to end the pandemic and improve global public health.



• Stakeholders also thought the CoVLP vaccine might require special handling and

shipping requirements because virus-like particles (VLPs) tend to be more fragile than

whole viral particles.

Description

GlaxoSmithKline (GSK) plc (Brentford, United Kingdom) and Medicago Inc (Quebec City,

Quebec, Canada) are jointly developing the adjuvanted, plant-based CoVLP vaccine against the

novel coronavirus.211 The CoVLP vaccine mimics the shape and dimensions of the virus,

displaying the SARS-CoV-2 spike protein on the surface of VLPs (assemblies of viral proteins

that present antigens in a manner similar to the native virus but do not incorporate genetic

material and, therefore, are noninfectious).211,212 By presenting viral antigens in a manner similar

to the virus, VLPs purportedly elicit a balanced immune response that is both antibody- and cell-

mediated.213,214

FDA has granted the CoVLP vaccine Fast Track designation. CoVLP is in a phase 2/3

randomized trial in 30 918 adults, with estimated completion in December 2021.215,216

Participants will receive 2 doses of placebo or 3.75 µg of CoVLP with AS03 adjuvant given 21

days apart. Results from a phase 1 randomized trial found that almost all of the patients receiving

both doses of adjuvanted CoVLP developed neutralizing antibody responses that were 10- to 50-

fold higher than levels seen in individuals recovering from COVID-19 infection. Pain at the

injection site, headache, and fatigue were the most common reactions, and most adverse events

were mild to moderate and of short duration.212









If found to be safe and effective for preventing COVID-19, the CoVLP vaccine might reduce

infection risk and improve health outcomes in the general population. If the vaccine helps

prevent severe COVID-19 infections, it could also reduce costs arising from treatment of severe

infections and related complications.

More broadly, another effective vaccine option could allow local leaders and health officials

to relax social-distancing protocols. If found to be safe and effective at preventing COVID-19,

the CoVLP vaccine could expand the knowledge base regarding the effectiveness of plant-based

manufacturing technology. Depending on its effectiveness and subsequent demand, shortages of

the CoVLP vaccine could emerge due to limited production capacity.



Between January 25, 2021, and February 26, 2021, six ECRI stakeholders, reflecting nursing,

research, health systems, health care generalist, and clinical engineering perspectives, provided

comments and ratings on this topic. The list below provides a summary of key stakeholder

perspectives.

• The availability of several safe, effective COVID-19 vaccines both domestically and

globally is a major requirement for successful vaccination programs intended to slow and

then halt the pandemic.

• Although funding worldwide vaccination programs will remain a challenge, the

emergence of more safe and effective COVID-19 vaccines could shorten global wait

times to receive a vaccine, potentially reducing disparities and improving global

population health.

• Long-term safety concerns about CoVLP remain because its specific development

technology has not been used before to produce vaccines.

• VLPs tend to be more fragile than whole viral particles, potentially making them more

susceptible to constant movement and drastic temperature changes that can occur during

transit. Thus, safe transportation and handling of CoVLP vaccine might require additional

precautions.


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