A systematic review comparing at-home diagnostic tests for SARS-CoV-2: Key points for pharmacy practice, including regulatory information.

BACKGROUND: Home-based rapid diagnostic testing can play an integral role in controlling the spread of coronavirus disease 2019 (COVID-19).
OBJECTIVES: This review aimed to identify and compare at-home diagnostic tests that have been granted Emergency Use Authorizations (EUAs) and convey details about COVID-19 diagnostic tests, including regulatory information, pertinent to pharmacy practice.
METHODS: The Food and Drug Administration (FDA) online resources pertaining to COVID-19 tests, EUAs, and medical devices were consulted, as were linked resources from FDA's webpages. Homepages of the 9 COVID-19 home tests with EUAs were comprehensively reviewed. PubMed literature searches were performed, most recently in May 2021, to locate literature about the identified home tests, as were searches of Google Scholar, medRxiv, and bioRxiv. Studies were included if they were performed at home or if subjects self-tested at study sites. Samples were collected by a parent or guardian for patients under 18 years of age. Positive percent agreement (PPA) and negative percent agreement (NPA) for the clinical diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was evaluated.
RESULTS: Limited data have been published for these home tests given that they are available through EUAs that do not require clinical trials. Fifteen studies were located from searching the literature, but only 2 met the inclusion criteria. Review of the home tests' websites yielded a single study for each test, with the 3 BinaxNOW platforms using the same study for their EUAs. The 9 COVID-19 home tests with EUAs as of May 7, 2021, include 3 molecular tests and 6 antigen tests. These tests had similar performance on the basis of PPA ranging from 83.5% to 97.4% and NPA ranging from 97% to 100%.
CONCLUSION: The 9 SARS-CoV-2 home tests demonstrated satisfactory performance in comparison with laboratory real time reverse-transcription polymerase chain reaction tests. The convenience and ease of use of these tests make them well-suited for home-based rapid SARS-CoV-2 testing.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening and diagnostic tests are a critical tool to help reduce disease transmission, and there is a crucial need for widely available rapid diagnostic tests for consumer use.

Several test types have been utilized under Emergency Use Authorizations (EUAs), including molecular, antigen, and serology tests.

Findings

Nine diagnostic tests have been granted EUA for at-home use, including 3 molecular tests: Lucira coronavirus disease 2019 (COVID-19) all-in-one test kit, Lucira CHECK-IT COVID-19 test kit, and Cue COVID-19 test for home and over-the-counter (OTC) use; and 6 antigen tests: BinaxNOW COVID-19 Ag card home test, BinaxNOW COVID-19 antigen self-test, BinaxNOW COVID-19 Ag card 2 home test, QuickVue at-home COVID-19 test, QuickVue at-home OTC COVID-19 test, and Ellume COVID-19 home test.

The 9 at-home tests currently available under EUAs show high positive percent agreement and negative percent agreement for identifying SARS-CoV-2.

Feelings of being unprepared and overwhelmed rippled throughout the world in the early days of the coronavirus disease 2019 (COVID-19) pandemic. As infections rapidly spread, scientists struggled to develop and distribute reliable diagnostic tests and establish meaningful testing protocols. In a scramble to develop diagnostic tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the Food and Drug Administration (FDA) expanded its Emergency Use Authorization (EUA) process to allow for more applicants to seek approval for tests. Even with these measures, unacceptable delays in testing continue and have furthered the confusion and panic caused by the pandemic.

Although vaccines are being administered in many countries, it is recognized that the world will need to contend with SARS-CoV-2 for the foreseeable future. With this reality, a critical need remains to diagnose COVID-19 quickly and accurately. Until more is known about immunity durability after infection and vaccination, tests allowing for minimal interaction of symptomatic individuals with others are needed. Several testing platforms have been utilized over the first year of the pandemic to improve testing access and reduce disease transmission risks (e.g., drive-thru testing centers). Although these services allow for high-volume, socially distanced testing, these models are somewhat inconvenient for patients and usually rely on polymerase chain reaction (PCR) tests that may have unacceptably long turnaround times. , To improve convenience, diagnostic laboratories have developed at-home collection kits allowing individuals to collect specimens at home to then send to a designated laboratory for testing, with 50 having EUAs as of May 7, 2021. Although these kits provide convenience and social distancing, their turnaround times are suboptimal. Since November 2020, multiple manufacturers have received EUA for complete at-home testing platforms. , In theory, these tests offer optimal efficiency and convenience while maintaining maximal social distancing. These home tests are a dramatic shift from early pandemic testing models, so little is known about them. The purpose of this systematic review is to identify at-home diagnostic tests for SARS-CoV-2 that currently have EUA in the United States and evaluate their diagnostic accuracy. Regulations impacting testing and key considerations that clinicians should be familiar with regarding these home tests are also discussed.

Regulatory matters

The Clinical Laboratory Improvement Amendments of 1988 (CLIA) established national quality standards for nonresearch laboratory testing performed on human-derived specimens. Under these regulatory standards for laboratory tests performed for the purposes of health assessment or for “diagnosis, prevention, or treatment,”7, 8, 9 CLIA defines roles for the Centers for Disease Control and Prevention (CDC), Center for Medicare and Medicaid Services (CMS), and FDA in supporting laboratory testing. Under CLIA, CMS is responsible for certifying laboratories and other facilities, including pharmacies, and ensuring compliance with testing standards. , CDC is responsible for technical oversight, developing technical standards, and maintaining laboratory quality. In this role, various guidelines are issued to ensure safety and quality. CDC’s Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens for COVID-19 provides critical information for health care providers offering point-of-care (POC) testing and specifies that pharmacists are considered health care providers under this guidance. FDA reviews and approves medical devices brought to the market. Once a medical test receives FDA approval, it is categorized on the basis of the complexity of methods required to run the test. Numerous factors are considered when assigning test complexity, including user interpretation requirements, calibration and quality control requirements, degree of independent judgment needed, difficulty of performance calculations, intricacy of methodologies, and degree of training needed to operate and run the test. On the basis of these elements, many tests are assigned moderate or high-level complexity and can only be run by laboratories certified to run tests of these complexities. A company may apply for a waived complexity status (i.e., CLIA-waived) if they believe that their test is simplistic enough, does not require training other than review of a product insert to perform, requires no or minimal interpretation or judgment, and presents little risk of erroneous results. By obtaining CLIA-waived status, a test may be performed in a nontraditional laboratory setting in possession of a CMS Certificate of Waiver, with pharmacies demonstrating a surge in these waivers since the pandemic began. In addition, manufacturers of CLIA-waived devices may seek clearance for home-use.

Typically, the approval process for a new test takes about 3-7 years. Section 564 of the Federal Food, Drug, and Cosmetic Act enables the FDA Commissioner to allow unapproved medical products or unapproved uses of approved medical products to be used in emergency situations. This process is referred to as EUA and allows FDA to facilitate the availability and use of medical measures needed during public health emergencies. , Granting EUA is different from FDA approval of a device. EUA may only be granted after a declaration by the U.S. Department of Health and Human Services (HHS) Secretary that circumstances exist justifying the authorization. In addition, FDA must determine that the following statutory criteria have been met: (1) use “for a serious or life-threatening condition,” (2) “evidence of effectiveness,” (3) favorable “risk-benefit analysis,” and (4) “no alternatives” exist. For FDA approval, a high standard of proof of effectiveness is required. For EUA, the standard of “may be effective” is considered; therefore, data from controlled clinical trials need not be available. For in vitro diagnostic devices, performance data to support the intended use may be derived from testing “fresh, contrived, banked, or archived specimens.”

All devices granted EUA are only authorized for use while the emergency declaration exists. Once an EUA declaration is terminated, all devices authorized during the emergency declaration are no longer available for use and must be removed from the market. However, after EUA termination, the device manufacturer may continue or initiate an FDA review for device approval.

Under the Public Readiness and Emergency Preparedness (PREP) Act, the HHS Secretary issued an emergency declaration for COVID-19 that provides “limited liability for activities related to medical countermeasures against COVID-19.” Included in this are EUA devices. Following this emergency declaration, as of May 2021, FDA has issued 370 EUAs for qualifying in vitro diagnostics tests targeting SARS-CoV-2. As of May 7, 2021, 270 of the tests are molecular tests, and 13 meet criteria for CLIA-waived status; 24 are antigen detection tests, and 19 meet criteria for CLIA-waived status; 76 are serology tests to detect SARS-CoV-2 antibodies, and 7 meet criteria for CLIA-waived status. , Since the initial emergency declaration, multiple amendments have been introduced, and General Counsel Advisory Opinions and Guidance documents from the HHS have been issued. Of particular significance for pharmacists are the Third Amendment and HHS Guidance documents that clarify the roles of pharmacists, pharmacy interns, pharmacy technicians, and pharmacies, which indicate that they are all covered under the PREP Act when performing POC diagnostic testing, vaccinations, and services considered SARS-CoV-2 countermeasures, provided regulatory requirements are met.21, 22, 23, 24, 25

Overview of SARS-CoV-2 test types and performance measures

In addition to understanding the regulatory matters surrounding SARS-CoV-2 testing, a basic understanding of SARS-CoV-2 test types and performance parameters is important for pharmacists who may be involved in test administration, distribution, and patient counseling. The 3 test types currently available include molecular tests, antigen tests, and serology tests.

Molecular diagnostic tests amplify and detect pathogen-specific genetic targets, detecting target SARS-CoV-2 genetic material in the case of COVID-19. For diagnosing SARS-CoV-2, PCR assays are most prevalent and typically exhibit high sensitivity, with sensitivity indicating the percentage of true positive results detected by the test [low false negative rate]. , Testing during the first few days of infection when viral loads may be small, or when there may be inadequate specimens, can lead to false negatives because there is inadequate SARS-CoV-2 genetic material for the tests to detect. A meta-analysis found an average test sensitivity of 95% for the studied rapid molecular assays. The same meta-analysis found an average test specificity of 98.9%, with specificity being the probability that a negative test result is truly negative (low false positive rate). , Although PCR-based tests have excellent sensitivity and specificity, they require expensive equipment and are prone to contamination. In addition, these tests are sometimes criticized as being too sensitive because they do not discriminate between viable pathogens and residual genetic fragments from nonviable virus. In other words, these tests can determine whether the disease is present in a patient but cannot determine whether it is contagious or not.

Antigen diagnostic tests detect proteins such as the spike protein, nucleocapsid protein, or both from viable virus. These assays are typically based on less expensive lateral flow technology. Many of these tests do not require analyzers or readers and are, therefore, less expensive and highly portable. The trade-off is that they tend to have lower analytical sensitivities, “i.e., require greater amounts of virus material to turn positive” than PCR tests. A meta-analysis found a wide range of test sensitivities for the studied antigen tests, with an average sensitivity of 56.2%. This same meta-analysis found good test specificity, with an average of 99.5% for the antigen tests studied. Even with low sensitivities, Larremore, an infectious disease modeler and proponent of frequent rapid testing for SARS-CoV-2 infection indicated, “Even low-sensitivity tests, which only catch people at the early and most-contagious stage of infection, could still be useful.” Indeed, antigen tests when administered when there are peak viral loads, when individuals are most likely to be infectious, reportedly exhibit sensitivity comparable to PCR tests.

Serologic tests detect antibodies to a virus, thus indicating whether there has been a recent or past infection. These tests, also called antibody tests, are not meant to detect active infection but rather can identify individuals who have already had the virus. Figure 1 depicts approximations of tests’ ability to detect viral infection as time progresses from infection onset through 4 weeks after infection.

Figure 1

Test method versus progression of infection. Abbreviations used: IgG, immunoglobulin G; IgM, immunoglobulin M; PCR, polymerase chain reaction; SARS-Cov-2, severe acute respiratory syndrome coronavirus 2. Image reused with permission from Spring Healthcare. Copyright 2020 Spring Healthcare. https://springhealthcare.org/sars-cov-2-antigen-rapid-test-swab/.

With the use of rapid diagnostic tests, it is essential to understand the impact of their performance characteristics as the intended use and pretest probability of disease fluctuate. When the sensitivity of a test is low and the pretest probability of disease is high, the test may return a higher rate of false negative results. This correlates with the negative predictive value (NPV) of a test or how good it is at ruling out a disease. In this scenario, one should confirm a negative test result when there is a high suspicion of disease with a more sensitive test like a laboratory-based PCR test, so a true infection is not missed. Conversely, a test with a relatively high specificity may result in a high rate of false positive tests when the pretest probability of disease is low. This correlates with the positive predictive value (PPV) of a test or how good the test is at ruling in a disease. In this case, it is prudent to confirm a positive result in an asymptomatic individual with a laboratory-based PCR test in an effort not to misdiagnose someone with COVID-19.

As the COVID-19 pandemic continues and SARS-CoV-2 continues to circulate for the foreseeable future, manufacturers have begun to expand access to tests for the general public. One solution is to enable individuals to collect and test specimens at home, allowing for complete at-home testing. Currently, 6 antigen tests and 3 PCR test have received EUAs for at-home testing.

Methods

Search strategies

FDA website documents and linked resources pertaining to COVID-19 tests, EUAs, and medical devices were consulted. Websites of the 9 COVID-19 home tests with EUAs were comprehensively reviewed. PubMed, Google Scholar, medRxiv, and bioRxiv literature searches were most recently performed in May 2021 for home tests issued EUAs. Database search details can be found in Appendix 1.

Appendix 1

Search strategies

Database/Website	Date of Most Recent Search	Search Terms	Search Limits	# of Results
PubMed	5/5/2021	(PCR or "polymerase chain reaction" or "nucleic acid amplification" or "SARS-CoV-2 nucleocapsid protein" or "molecular diagnostic" or "molecular diagnostics" or "molecular diagnosis" or "Pathology, Molecular" or antigen or nucleocapsid or "lateral flow immunoassay" or immunoassay or "RT-LAMP" or LAMP assay or viable or "non-viable" or "COVID-19 Testing" or "Diagnostic Techniques and Procedures" or "rapid diagnostic tests" or "rapid diagnostic testing") AND ("COVID 19 Testing" or "COVID-19 Testings" or "Testing, COVID-19" or "SARS Coronavirus 2 Testing" or "COVID-19 Virus Testing" or "COVID 19 Virus Testing" or "COVID-19 Virus Testings" or "Testing, COVID-19 Virus" or "Virus Testing, COVID-19" or "COVID19 Testing" or "COVID19 Testings" or "Testing, COVID19" or "COVID19 Virus Testing" or "COVID19 Virus Testings" or "Testing, COVID19 Virus" or "Virus Testing, COVID19" or "SARS-CoV-2 Testing" or "SARS CoV 2 Testing" or "SARS-CoV-2 Testings" or "Testing, SARS-CoV-2" or "Coronavirus Disease 2019 Testing" or "2019 Novel Coronavirus Disease Testing" or "2019 Novel Coronavirus Testing" or "2019-nCoV Disease Testing" or "2019 nCoV Disease Testing" or "2019-nCoV Disease Testings" or "Disease Testing, 2019-nCoV" or "Testing, 2019-nCoV Disease" or "2019-nCoV Infection Testing" or "2019 nCoV Infection Testing" or "2019-nCoV Infection Testings" or "Infection Testing, 2019-nCoV" or "Testing, 2019-nCoV Infection" or "COVID-19 Diagnostic Testing" or "COVID 19 Diagnostic Testing" or "COVID-19 Diagnostic Testings" or "Diagnostic Testing, COVID-19" or "Severe Acute Respiratory Syndrome Coronavirus 2 Testing" or "Coronavirus Disease-19 Testing" or "Coronavirus Disease 19 Testing" or "Coronavirus Disease-19 Testings" or "Testing, Coronavirus Disease-19" or "2019-nCoV Testing" or "2019 nCoV Testing" or "2019-nCoV Testings" or "Testing, 2019-nCoV") AND ("home test"[Title/Abstract] OR "home tests"[Title/Abstract] OR "home testing"[Title/Abstract] OR "home use"[Title/Abstract] OR "self-collect"[Title/Abstract] OR "self-collected"[Title/Abstract] OR "self-administered"[Title/Abstract] OR "Direct-To-Consumer Screening[Title/Abstract] AND Testing"[Title/Abstract] OR "at-home"[Title/Abstract] OR "Abbott BinaxNOW"[Title/Abstract] OR Abbott[Title/Abstract] OR "Ellume COVID-19 home test"[Title/Abstract] OR Ellume[Title/Abstract] OR "Lucira COVID-19 All-in-One"[Title/Abstract] OR Lucira[Title/Abstract] OR QuickVue OR "Cue COVID-19")	10/1/2020 -	199
medRxiv & bioRxiv	5/5/2021	∗ Searching for all proprietary names with Boolean operator OR between each proprietary name caused erroneous results [BinaxNOW OR Lucira OR Ellume OR “QuickVue At Home” OR "Cue COVID-19"] so each proprietary name was searched individually
medRxiv & bioRxiv	5/5/2021	BinaxNOW	Date Posted:	41
			10/1/2020 – 5/5/2021
medRxiv & bioRxiv	5/5/2021	Lucira	Date Posted:	3
			10/1/2020 – 5/5/2021
medRxiv & bioRxiv	5/5/2021	Ellume	Date Posted:	12
			10/1/2020 – 5/5/2021
medRxiv & bioRxiv	5/5/2021	“QuickVue At Home”	Date Posted:	0
			10/1/2020 – 5/5/2021
medRxiv & bioRxiv	5/5/2021	"Cue COVID-19"	Date Posted:	0
			10/1/2020 – 5/5/2021
Google Scholar	5/5/2021	(COVID-19 OR SARS-CoV-2) AND (BinaxNOW OR Lucira OR Ellume OR "QuickVue At Home" OR "Cue COVID 19")	Articles added in the last year	285

Inclusion criteria

To detect literature about the SARS-CoV-2 home tests with current EUAs, all PubMed, Google Scholar, medRxiv, and bioRxiv results that specifically mentioned one or more tests’ proprietary name(s) were extracted for review. Studies were included if the samples were self-collected (or collected by a parent or guardian for patients under 18 years of age) and evaluated the positive percent agreement (PPA) and negative percent agreement (NPA) for the clinical diagnosis of SARS-CoV-2 virus. Studies from the home tests manufacturers’ websites were also selected for inclusion because EUA does not require clinical trials and limited data is available for these tests.

Results

Searches of PubMed, Google Scholar, medRxiv, and bioRxiv yielded 15 unique studies after de-duplication.36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 Studies identified can be found in Appendix 2. Fourteen of the studies examined the BinaxNOW platform, and 1 examined the Cue COVID-19 Test. Two studies met inclusion criteria. , Seven studies were identified in the manufacturers’ EUA labeling.51, 52, 53, 54, 55, 56, 57, 58, 59 The 3 at-home BinaxNOW platforms all used the same study for their EUA.51, 52, 53 Data from all 7 manufacturers’ studies were included in the qualitative systematic review.51, 52, 53, 54, 55, 56, 57, 58, 59

Appendix 2

Published studies and preprint studies examining home tests’ platforms

Author(s), Year, Publication Status	Test Platform	Included/Excluded	Inclusion/Exclusion Reason
Aranda-Diaz et al.1, Preprint	BinaxNOW COVID-19 Antigen Card	Excluded	Not self-collection of test samples
Donato et al.2, Published	Cue COVID-19 Test for Home and Over The Counter (OTC) Use	Excluded	Not self-collection of test samples
Forde and Ciupe3, Published	BinaxNOW COVID-19 Antigen Card	Excluded	Modelling study
James et al.4, Published	BinaxNOW COVID-19 Antigen Card	Excluded	Not self-collection of test samples
Kuo et al.5, Published	BinaxNOW COVID-19 Antigen Card	Excluded	Samples from previously frozen specimens
Okoye et al.6, Published	BinaxNOW COVID-19 Antigen Card	Included	Self-collection of test samples
Peng et al.7, Preprint	BinaxNOW COVID-19 Antigen Card	Excluded	Not self-collection of test samples
Perchetti et al., 2020, Published	BinaxNOW COVID-19 Ag CARD	Excluded	Used de-identified specimens at the laboratory
Pilarowski et al.8, Published	BinaxNOW COVID-19 Ag CARD	Excluded	Not self-collection of test samples
Pilarowski et al.9. Published	BinaxNOW COVID-19 Ag CARD	Excluded	Not self-collection of test samples
Pollock, Jacobs and Tran, 2021, Published	BinaxNOW COVID-19 Ag CARD	Excluded	Not self-collection of test samples
Prince-Guerra et al.10, Published	BinaxNOW COVID-19 Ag Card	Excluded	Not self-collection of test samples
Reddy and Das11, Preprint	BinaxNOW COVID-19 Ag Card	Excluded	Modelling study
Shah et al., 2021, Preprint	BinaxNOW COVID-19 Ag Card	Included	Self-collection of test samples
Sood et al.12, Published	BinaxNOW COVID-19 Ag Card	Excluded	Not self-collection of test samples

Risk of bias

Because all of the tests have been made available through EUA, the data used to obtain the EUAs were from interim analyses;51, 52, 53, 54, 55, 56, 57, 58, 59 therefore, the sample sizes were smaller, leading to issues with selection bias and potential issues with the ability to extrapolate the data to expanded populations. In addition, the clinical data have only been published in the manufacturers’ literature, so while FDA has reviewed it, it has not gone through the rigorous peer-review process that occurs when studies are published in medical journals. In addition, many of the details needed to fully assess bias are missing (e.g., missing demographic data make it difficult to know which patient populations are represented in the studies). Therefore, there is a high risk of bias in the studies included in this systematic review.

Synopsis of test characteristics

There are 9 COVID-19 home tests at the time this article was written, some of which are the same testing platform with different availabilities or indications. , 51, 52, 53, 54, 55, 56, 57, 58, 59 Three of the tests are molecular (2 Lucira and 1 Cue),55, 56, 57 and 6 are antigen-based (Ellume, 3 BinaxNOW, and 2 QuickVue).51, 52, 53, 54 , , A full comparison of the molecular tests can be found in Table 1 , and a full comparison of the antigen tests can be found in Table 2 .

Table 1

Comparison of at-home molecular COVID-19 tests51, 52, 53, 54, 55, 56, 57, 58, 59

Device characteristic	Lucira COVID-19 all-in-one test kit	Lucira CHECK-IT COVID-19 test kit	Cue COVID-19 test for home and OTC use
Emergency Use Authorization date	November 17, 2020	April 9, 2021	March 20, 2021
Manufacturer	Lucira	Lucira	Cue Health
Requires prescription	Yes	No (OTC version of Lucira COVID-19 all-in-one test kit)	No
Principle of test procedure	Qualitative molecular amplification	Qualitative molecular amplification	Qualitative molecular amplification
Specimen sample	Nasal swab	Nasal swab	Nasal swab
Authorized age for use	Self-collected: ≥14 y	Self-collected: ≥14 y	Self-collected: ≥18 y
		Adult-collected: ≥2 y	Adult-collected: ≥2 y
Requires observation by telehealth proctor	No	No	No
Indication for use	Suspected COVID-19 by health care provider	With or without symptoms or other epidemiologic reason to suspect COVID-19	With or without symptoms or other epidemiologic reason to suspect COVID-19
Instructions for use	Open kit	Open kit	Set up Monitoring System
	Insert batteries	Insert batteries	Open kit
	Insert vial into test unit	Insert vial into test unit	Insert test cartridge into reader
	Nasal swab	Nasal swab	Nasal swab with wand
	Inset nasal swab in vial	Inset nasal swab in vial	Insert nasal swab into cartridge
	Stir vial contents	Stir vial contents
	Close vial and press down	Close vial and press down
Results	Appears on display	Appears on display	Appears in mobile app
Results automatically reported to public health authorities	No	No	Yes
Differentiates between SARS-CoV-1 and SARS-CoV-2	Yes	Yes	No
Endogenous interfering substance at tested concentrations	None	None	None
Cross-reactivity with other organisms	No	No	No
Time to result	11–30 min	11–30 min	approximately 20 min
Requirements	None	None	Cue Health Monitoring System
			Mobile smart device
			Cue Health mobile app
Price	$55	$55	Not set yet
When and how available	Currently available; kit sent to home after provider submits prescription	Currently commercially available	Availability unknown
Same test available for nonhome POC use	Yes	Yes	Yes

Abbreviations used: COVID-19, coronavirus disease 2019; OTC, over-the-counter; POC = point of care; SARS-CoV-1, Severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, Severe acute respiratory syndrome coronavirus.

Table 2

Comparison of at-home antigen COVID-19 tests51, 52, 53, 54, 55, 56, 57, 58, 59

Device characteristic	Ellume COVID-19 home test	BinaxNOW COVID-19 Ag card home test	BinaxNOW COVID-19 Ag card 2 home test	BinaxNOW COVID-19 antigen self-test	QuickVue at-home COVID-19 test	QuickVue at-home OTC COVID-19 test
Emergency use authorization date	December 15, 2020	December 16, 2020	March 31, 2021	March 31, 2021	March 1, 2021	March 31, 2021
Manufacturer	Ellume	Abbott	Abbott	Abbott	Quidel	Quidel
Requires prescription	No	Yes	No	No	Yes	No
Principle of test procedure	Qualitative lateral flow immunoassay	Qualitative lateral flow immunoassay	Qualitative lateral flow immunoassay	Qualitative lateral flow immunoassay	Qualitative lateral flow immunoassay	Qualitative lateral flow immunoassay
Specimen sample	Midturbinate nasal swab	Nasal swab	Nasal swab	Nasal swab	Nasal swab	Nasal swab
Authorized age for use	Self-collected: ≥16 y	Self-collected: ≥15 y	Self-collected: ≥15 y	Self-collected: ≥15 y	Self-collected: ≥14 y	Self-collected: ≥14 y
	Adult-collected: ≥2 y	Adult-collected: ≥4 y	Adult-collected: ≥2 y	Adult-collected: ≥2 y	Adult-collected: ≥8 y	Adult-collected: ≥2 y
Requires observation by telehealth proctor	No	Yes	Yes	No	No	No
Indication for use	With or without symptoms or other epidemiologic reasons to suspect COVID-19	Suspected COVID-19 by health care provider within first 7 d of symptom onset	Screening use with serial testing in patients with or without symptoms or other epidemiologic reasons to suspect COVID-19	Screening use with serial testing in patients with or without symptoms or other epidemiologic reasons to suspect COVID-19	Suspected COVID-19 by health care provider within first 6 d of symptom onset	Screening use with serial testing in patients with or without symptoms or other epidemiologic reasons to suspect COVID-19
Instructions for use	Open kit	Open kit	Open kit	Open kit	Open kit	Open kit
	Open app/answer questions	Open app/answer questions	Open app/answer questions	Add reagent to top of card	Open tube	Open tube
	Connect analyzer to phone	Add reagent to top of card	Add reagent to top of card	Nasal swab	Nasal swab	Nasal swab
	Apply processing fluid to dropper	Nasal swab	Nasal swab	Insert nasal swab to bottom card	Insert nasal swab in tube	Insert nasal swab in tube
	Nasal swab	Insert nasal swab in card	Insert nasal swab to bottom card	Perform test twice over 3 d with 36 h between tests if serial testing	Insert test strip into tube	Insert test strip into tube
	Insert nasal swab in dropper	Scan results with app	Scan results with app		Remove test strip	Remove test strip
	Apply dropper fluid to analyzer		Perform test twice over 3 d with 36 h between tests if serial testing			Perform test twice over 2–3 days with 24–36 h between tests if serial testing
Results	Appear in mobile app	Unofficial: visual read on card	Unofficial: visual read on card	Visual read on card	Visual read on strip	Visual read on strip
		Official: appears in mobile app after outside interpretation	Official: appears in mobile app after outside interpretation
Results automatically reported to public health authorities	Yes	Yes	Yes	No	No	No
Differentiates between SARS-CoV-1 and SARS-CoV-2	No	No	No	No	No	No
Endogenous interfering substance	None	Mupirocin	Mupirocin	Mupirocin	None	None
Cross-reactivity with other organisms	No	No	No	No	No	No
Time to result	15 min	Unofficial: 15 min	15 min	15 min	10 min	10 min
		Official: approximately 20 min
Requirements	Smart phone with iOS or Android Ellume COVID-19 application	Smart phone with iOS or Android Navica application	Smart phone with iOS or Android Navica application	N/A	N/A	N/A
Price	$38.99	$50/1 test; $150/6- pack	Not set yet	$20–24	Not set yet	Not set yet
When and how available	Currently available at select CVS stores	Currently available from Optum (1) or eMed (6)	Availability unknown	Currently commercially available	Availability unknown	Availability unknown
Same test available for nonhome POC use	No	Yes	Yes	Yes	Yes	Yes

Abbreviations used: POC, point of care; COVID-19, coronavirus disease 2019; OTC, over-the-counter; SARS-CoV-1, Severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, Severe acute respiratory syndrome coronavirus; iOS, internet operating system; N/A, not applicable.

Six of the tests are available OTC, and 3 are only available via prescription.51, 52, 53, 54, 55, 56, 57, 58, 59 The BinaxNOW Ag Card, QuickVue at-Home, and Lucira All-in-One tests are only indicated for patients suspected of having COVID-19 (e.g., symptomatic), , , and the remaining 6 tests are indicated for both symptomatic and asymptomatic patients.52, 53, 54 , , All test results can be read on the test platform’s display or in their mobile application.51, 52, 53, 54, 55, 56, 57, 58, 59 Although results for Cue will appear in the mobile application, patients will need to insert the cartridge into an external reader. BinaxNOW Ag Card and Ag Card 2 also have an external step where the results will only appear in the mobile application after they have been interpreted by an outside individual, although there is an unofficial visual reader on the card. , All the tests should be stored at room temperature and can be discarded in the trash with proper disposal of the batteries for the machines requiring their use.51, 52, 53, 54, 55, 56, 57, 58, 59 Patients should not discard the external reader for the Cue test as it will be needed to read all subsequent Cue tests.

Patients can get technical support for help using the devices from the respective manufacturer.51, 52, 53, 54, 55, 56, 57, 58, 59 The selection of an at-home test will be largely dependent on availability and patient characteristics and preferences. All the tests have some limitations of use as well, which can vary depending on the type of test. False negative results can occur with all the tests, particularly if they are not performed correctly. False negatives can also occur with the antigen tests if the antigen level is below the detection level of the test. Positive test results cannot be used to rule out the presence of other pathogens. In addition, the antigen tests can detect viable and nonviable virus, so patients may test positive even if they do not have an active infection. Finally, the predictive values of the test can be impacted by the prevalence of the disease, so the reliability of the test results can be significantly different in regions where the prevalence is high compared with areas where the prevalence is low.

Synopsis of test performances

Given the current nature of COVID-19 testing and the lack of a consensus gold standard reference test, the manufacturers of these home tests used validation standards required by FDA for EUAs.51, 52, 53, 54, 55, 56, 57, 58, 59 As a result, the measures of sensitivity and specificity may not be appropriate to use in some situations. Similar statistics can be used in place of sensitivity and specificity to show that the tests were evaluated using comparable tests rather than a true reference standard. In this scenario, sensitivity is replaced with PPA, and specificity is replaced with NPA.

All manufacturers’ studies of the home test kits’ performances were prospective studies.51, 52, 53, 54, 55, 56, 57, 58, 59 The PPA for the 9 home tests ranged from 83.5% (QuickVue At-Home) to 97.4% (Cue COVID-19), and the NPA ranged from 97% (Ellume) to 100% (BinaxNOW). It is important to note that all 3 at-home BinaxNOW tests use the same platform, so the same data sets were used to receive their EUA. See Table 3 for a summary of the studies and additional statistics.

Table 3

Test performance versus laboratory molecular comparator51, 52, 53, 54, 55, 56, 57, 58, 59

Study element	BinaxNOW COVID-19 Ag card home test, BinaxNOW COVID-19 Ag 2 card home test, BinaxNOW COVID-19 antigen testa	Ellume COVID-19 home test	QuickVue at-home COVID-19 test	QuickVue At-Home OTC COVID-19 test	Lucira COVID-19 all-in-one test kit	Lucira CHECK-IT COVID-19 test kit	Cue COVID-19 test for home and OTC use
Study design	United States multisite prospective	United States multisite prospective	United States multisite prospective	United States prospective	Prospective	Prospective	United States multisite prospective
Population	Present with COVID-19 sx within 7 d of onset	All-comers study (asx and sx), age ≥ 2 y	Present with COVID-19 sx within 6 d of onset	Present with COVID-19 sx within 6 d of onset	Present with COVID-19 sx	All-comers (asx and sx)	All-comers (asx and sx), age ≥ 2 y
No. self-tested samples	53 sx pts	198 pts (64 sx, 134 asx)	161 sx pts	306 sx pts 44 asx pts	101 sx pts	404 pts	273 pts
Main efficacy results	PPA: 91.7% (95% CI 73%–98.9%)	Overall PPA: 95% (95% CI 82%–99%)	PPA: 84.8% (95% CI 71.8–92.4%)	PPA: 83.5% (95% CI 74.9%–89.6%)	PPA: 94.1% (95% CI 85.5%–98.4%)	Overall PPA: 91.7% (95% CI 85.6%–95.8%)	Overall PPA: 97.4% (95% CI 86.5%–99.5%)
	NPA: 100% (87.7%–100%)	Overall NPA: 97% (95% CI 93%–99%)	NPA: 99.1% (95% CI 95.2%–99.8%)	NPA: 99.2% (95% CI 97.2%–99.8%)	NPA: 98% (95% CI 89.4%–99.9%)	Overall NPA: 98.2% (95% CI 95.8–99.4%)	Overall NPA: 99.1% (95% CI 96.9%–99.8%)
		Sx PPA 96% (95% CI 81%–99%)				Sx: PPA: 94.1% (95% CI 85.5%–98.4%)	Sx PPA: 96.4% (95% CI 82.3%–99.4%)
		Sx NPA 100% (95% CI 91%–100%)				Sx: NPA: 98% (95% CI 89.4%–99.9%)	Sx NPA: 98.2% (95% CI 93.6%–99.5%)
		Asx PPA 91% (95% CI 62%–98%)				Asx PPA 90.1% (95% CI 81.5%–95.6%)	Asx PPA: 100% (95% CI 72.23%–100%)
		Asx NPA 96% (91%–98%)				Asx NPA: 98.2% (95% CI 95.5%–99.5%)	Asx NPA: 100% (95% CI 97.0%–100%)
Results based on days of symptoms	Self-tested: not studied	Sx: PPA 100% up to 6 d, then 96%, NPA 100% up to > 7 d	Not studied	Not studied	Not studied	Not studied	Not studied
Additional efficacy resultsb	PPV: 100% (95% CI not calculated)	Overall PPV: 87.5% (74.6%–94.3%)	PPV: 97.5% (84.7%–99.6%)	PPV: 97.6% (91%–99.4%)	PPV: 98% (87.3%–99.7%)	Overall PPV: 96% (91%–98.3%)	Overall PPV: 94.9% (82.3%–98.7%)
	NPV: 93.3% (78.8%–98.2%)	Overall NPV: 98.7% (95.3%–99.7%)	NPV: 94.2% (89.2%–97%)	NPV: 94% (90.9%–96.1%)	NPV: 94.2% (84.5%–98%)	Overall NPV: 96% (93.2%–97.7%)	Overall NPV: 99.6% (97.1%–99.94%)
	LR +: infinity	Overall LR +: 30.5 (12.8–72.4)	LR +: 97.5 (13.8–688.9)	LR +: 105.63 (26.49–421.3)	LR+: 47.06 (6.75–327.97)	LR+: 49.87 (20.89–119.02)	LR+: 113.43 (28.51–451.32)
	LR–: 0.083 (0.022–0.314)	Overall LR–: 0.06 (0.01–0.21)	LR–: 0.15 (0.08–0.3)	LR–: 0.17 (0.11–0.26)	LR–: 0.06 (0.02–0.18)	LR–: 0.08 (0.05–0.15)	LR–: 0.03 (0–0.18)
		Sx PPV: 100% (95% not calculated)				Sx PPV: 98% (87.3%–99.7%)	Sx PPV: 93.1% (77.3%–98.2%)
		Sx NPV: 97.4% (84.8%–99.6%)				Sx NPV: 94.2% (90.2%–98.9%)	Sx NPV: 99.1% (94%–99.9%)
		Sx LR+: infinity				Sx LR+: 47.06 (6.75–327.97)	Sx LR+: 53.04 (13.41–209.79)
		Sx LR–: 0.04 (0.01–0.26)				Sx LR–: 0.06 (0.02–0.18)	Sx LR–: 0.04 (0.01–0.25)
		Asx PPV: 66.7% (45.4%–82.8%)				Asx PPV: 94.8% (87.3%–98%)	Asx PPV: 100% (95% CI not calculated)
		Asx NPV: 99.2% (90.5%–98.3%)				Asx NPV: 96.5% (93.4%–98.1%)	Asx NPV: 100% (95% CI not calculated)
		Asx LR+: 22.36 (9.29–53.84)				Asx LR+: 50.02 (18.89–132.45)	Asx LR+: infinity
		Asx LR–: 0.09 (0.01–0.61)				Asx LR –: 0.1 (0.05–0.19)	Asx LR–: 0 (95% CI not calculated)

Abbreviations used: Asx, asymptomatic; LR–, likelihood ratio for negative test result; LR+, likelihood ratio for positive test result; NPV, negative predictive value; PPV, positive predictive value; Sx, symptomatic; COVID-19, coronavirus disease 2019; OTC, over-the-counter; PPA, positive percent agreement; NPA, negative percent agreement.

Because all BinaxNOW diagnostic tests are the same platform with different Emergency Use Authorizations, the same data sets were used to support each test’s Emergency Use Authorization.

Calculated using the MedCalc Diagnostic Test Evaluation Calculator (2021). https://www.medcalc.org/calc/diagnostic_test.php.

Given that the BinaxNOW tests (home and nonhome) all use the same platform, 2 studies using the nonhome version of BinaxNOW (BinaxNOW Ag Card) met inclusion criteria for this systematic review. One study evaluated the BinaxNOW Ag Card test in asymptomatic, college-aged students in November 2020. Students (n = 2638) were instructed to self-swab under the direct observation of trained individuals at a college screening event. Whereas the NPA was the same for the home tests (100%; [95% CI 99%–100%]), the PPA was significantly lower (53.3%; [95% CI 39.1%–67.1%]). This suggests that a negative test in asymptomatic patients may not be effective in ruling out the disease. Similar findings were found by Shah et al. who studied the BinaxNOW Ag Card test in a community testing site where patients were observed self-swabbing. In both symptomatic and asymptomatic patients, they found a PPA of 77.2% (95% CI, 72.4%– 81.6%) and an NPA of 99.6% (95% CI 99.2%–99.8%). The PPA for asymptomatic patients was 78.6% (73.4%–83.3%) compared with 81.9% (95% CI 76.5%–86.5%) in patients who had symptoms within 7 days of testing. In addition, they evaluated the potential benefits of serial testing in the same visit. They only found a similar PPA (81.4%; [95% CI 76.8%–85.5%]) for the repeat test, suggesting that serial testing at the same visit is not warranted (Table 3).

Discussion

Perfection is defined as “an unsurpassable degree of accuracy or excellence.” In medicine and science, we are trained to seek perfection in our instruments, analytical approach, and solutions. Unfortunately, we can become obsessed with striving for perfection and lose sight of our true goals. During World War II, Sir Robert Alexander Watson-Watt, developer of the early warning radar system used in Britain, was a believer in the “cult of the imperfect.” He was often quoted as saying, “Give them the third best to go on with; the second best comes too late, the best never comes.” This suggests that rather than waiting for the perfect, which may never come, we can succeed using an imperfect option. This idea holds true now, as we grapple with controlling the spread of SARS-CoV-2. If we wait for development of the perfect SARS-CoV-2 test, the loss of life and prevention of spread would be horrific. Therefore, we need to embrace the technologies we have at our disposal and use them to optimize their value.

Many in vitro SARS-CoV-2 diagnostic tests have received EUA since the beginning of the pandemic. These tests employ methods including PCR and antigen detection using a variety of platforms requiring a range of technical expertise, equipment, and expense. If we seek perfection, the question should be asked as to what makes a test perfect. Is perfection based on sensitivity and specificity of the assay? What if, in order to obtain analytical perfection, the procedures use an expensive analyzer and take 3 days to get results? Would that test still be considered perfect? If a comparator test had lower sensitivity and specificity but only cost $5 to perform and gave results within 15 minutes, would that test be imperfect? A companion philosophy to the cult of the imperfect that we as clinicians should embrace is the concept of situational relevancy. Simply put, situational relevancy is the realization that there is not a single correct solution to a problem with multiple variables. Rather, the correct solution for a given problem changes as the variables change. As an example, think about 2 SARS-CoV-2 testing scenarios. In the first scenario, we wish to detect SARS-CoV-2 in a limited number of hospitalized patients exhibiting symptoms of COVID-19. The goal for this scenario is to identify infected individuals for quarantine. Given these conditions, it seems that a test with high sensitivity and specificity would be important, and we may be willing to sacrifice turnaround time to improve these characteristics. In addition, because we would only be using this test on a relatively small population and given that the cost of a patient in an isolation room would be high, we may find that using a more expensive test would be cost-effective if performance characteristics were maximized. In the second scenario, we wish to screen asymptomatic individuals for SARS-CoV-2 to minimize the chance that they would infect co-workers. In this scenario, we understand that the pretest probability of having SARS-CoV-2 is low and the likelihood of detecting an individual with infection is low. In addition, people are to be screened 3 times a week before they may enter a building. Under this set of variables, being able to rule out the presence of the virus would seem more important that detecting the actual virus. Since the pretest probability of being infected with SARS-CoV-2 is low, any positive test result would likely need confirmation to rule out a false positive. Furthermore, because individuals are being tested 3 times a week, cost would be an appreciable consideration regarding the long-term application of a test system. Lastly, if a negative result is needed before a worker is allowed to go into a workspace, then speed is a critical factor in determining the utility of a test. Thus, even though the underpinning goal of detecting SARS-CoV-2 is the same in the 2 scenarios, the desirable characteristics of the “perfect” test is highly situational.

The best indicator of situational value is likely to be the PPV and NPV associated with the tests rather than their sensitivity and specificity. Sensitivity and specificity are fixed performance characteristics of each of the tests and do not account for pretest probability of the patient having or not having SARS-CoV-2. Therefore, they provide limited information on the real-world utility of the tests. Examples of the situational relevance of SARS-CoV-2 antigen tests was recently demonstrated in 2 studies examining the performance of antigen tests for SARS-CoV-2. , In both reports, the PPV and NPV were high among symptomatic individuals (high pretest probability). Similarly, the PPV decreased and NPV increased for each test among those with no symptoms. , These observations yield important information regarding use of these tests that can be extrapolated to home tests. Among symptomatic individuals, a positive test result is highly predictive of the presence of SARS-CoV-2 and can help diagnose an infection. However, because the NPV of tests under these circumstances is less than 100%, a negative test in a patient with symptoms should be confirmed with a laboratory-based PCR test. On the other hand, if a home test were to be used for screening in an asymptomatic population, their value as a diagnostic test would decrease (lower PPV). Therefore, a positive test result would likely need confirmation with laboratory-based PCR. However, in this scenario, a negative test can provide a strong indication that infection is not present, and the likelihood that the individual is infectious is low (high NPV).

Currently, some home tests are only authorized for use among those who are symptomatic or suspected of having COVID-19; they have the potential to assist in making a diagnosis. Accordingly, the use of these tests in a home environment in an asymptomatic individual would be outside the EUA of these tests. However, there is a reasonable probability that these tests may be used outside of their authorizations, not just those with EUAs for both symptomatic and asymptomatic individuals. One element that will require constant attention is the performance of these tests against emerging SARS-CoV-2 variants. Although the known variants are believed to only possess alterations in spike proteins, the impact of these changes on the performance of the current home-use tests is not fully known. Furthermore, additional structural and genetic changes are likely to occur, so constant evaluation of tests against new variants must continue to maintain the performance integrity of the tests.

Despite several possible shortcomings, home tests are likely to play a large role during the COVID-19 pandemic. There is a major convenience factor of home tests, considering the capability to purchase a test before symptom onset. Having a test readily available reduces the fear burden for vulnerable patients, those without transportation, and the risk of a long result time. The ability of individuals to run a test at home without venturing into public for testing and risking viral exposure or exposing others to SARS-CoV-2 is an important advantage of these tests. In addition, the convenience, quick results, and relatively low-cost of home tests are ideal for frequent, longitudinal screenings to clear individuals for work, school, or travel. Laboratory or pharmacy-based testing are inferior to home tests with respect to these variables. Insurance companies may reimburse patients who purchase at-home tests. With rapid changes occurring throughout the pandemic, it is too soon to recommend one test over the other. All tests have their various efficacies, and which test is chosen should be based on patient preference, ease, and symptomatology.

Because some at-home tests require a prescription and others can be purchased OTC at local pharmacies, it is important that pharmacists be familiar with these tests. Table 4 lists common questions that pharmacists may be asked regarding these tests. Because only BinaxNOW requires the user to be supervised by a telehealth proctor, many questions related to specimen collection, test interpretation, and post-test actions may arise. Pharmacists should be able to address these questions for the currently authorized tests and be prepared for the marketplace entry of more SARS-CoV-2 home tests. In addition, pharmacists should be aware of the regulatory stipulations, particularly CLIA regulations, and understand them before physically assisting with specimen collection and test interpretation. A CLIA Certificate of Waiver may be necessary to perform or assist with performing these tests, and physically assisting with these tests may be precluded, even in CLIA-waived settings, because tests authorized for home use are not automatically authorized for use in CLIA-waived settings. Finally, the pharmacist must be able help patients understand when confirmatory testing is required and where that can be completed.

Table 4

Pharmacy care model51, 52, 53, 54, 55, 56, 57, 58, 59

COVID-19 home testing pharmacy care model: Key counseling points
What are the symptoms of COVID-19?	Fever, acute respiratory illness (cough, dyspnea), chills, myalgias, headache, sore throat, loss of taste/smell, nausea and vomiting, or diarrhea
Do I need to have symptoms of COVID-19 in order to home test myself?	Lucira all-in-one, BinaxNOW Ag Card, QuickVue at-home: COVID-19 must be suspected by health care providerLucira check-it, Cue, Ellume, BinaxNOW Ag Card 2, BinaxNOW antigen self-test, QuickVue at-home OTC: with or without COVID-19 symptoms
Do I need a prescription to get a COVID-19 home test?	The current at-home tests that do NOT require a prescription are Lucira check-it, Cue, Ellume, BinaxNOW 19 Ag Card 2, BinaxNOW antigen self-test, and QuickVue at-home OTC (the tests that are available for both symptomatic and asymptomatic testing are the ones that do not require a prescription).
How do I administer a COVID-19 home test with the nasal swab?	Stick the nasal swab into one nostril. Rotate swab for about 5 seconds and repeat process within the other nostril. It is important to insert the same swab into both nostrils for an accurate sample with most tests.
I’m worried about administering a COVID-19 home test without someone’s help.	If you’re worried about doing the test alone, BinaxNOW Ag Card and Ag Card 2 require a telehealth proctor to be present to assist with proper nasal swab technique along with reading results. Feel free to also ask your local pharmacist for guidance on how to administer or look online for administration videos on the manufacturer website.
Does the nasal swab hurt?	No. The nasal swab may cause some discomfort or tickling feeling, but it should not cause puncturing or any sharp pains. Do not insert the swab any further if experiencing pain.
Which home testing device is the most efficacious?	All home testing kits with a current EUA are similar in efficacy, with QuickVue at-home having the lowest positive percent agreement rate (83.5%), and Cue COVID-19 test for home and OTC use having the highest (97.4%). Ellume has the lowest negative percent agreement (97%), and the 3 BinaxNOW home tests have the highest (100%).
How long will it take to receive results?	Results vary on the basis of test, ranging from 11–30 min.
The test is positive, now what?	Tell your health care provider and stay in contact with them throughout the illness. To avoid spreading the virus, follow CDC recommendations and isolate yourself from others. Potential for a PCR-based confirmatory test may be indicated.
The test is negative, now what?	A negative result means the SARS-CoV-2 was not found in your specimen. If you took the test while experiencing symptoms, a negative result usually means your current illness is not COVID-19. False negatives are possible, meaning you are positive for COVID-19, even though the test result stated negative. Discuss your symptoms and test results with your health care provider to determine whether follow-up testing is necessary
The test is invalid or there was an error, now what?	If the display shows invalid result or test error, the test didn’t perform properly. Refer to the package insert and contact the manufacturer for assistance

COVID-19, coronavirus disease 2019; SARS-Cov-2, severe acute respiratory syndrome coronavirus 2; CDC, Centers for Disease Control and Prevention; PCR, polymerase chain reaction; OTC, over-the-counter.

Conclusion

SARS-CoV-2 tests authorized for home use are not perfect; however, they represent a valuable resource in our effort to halt the current pandemic. The SARS-CoV-2 home tests examined in this review demonstrated satisfactory performance in comparison with laboratory RT-PCR tests. Owing to their simplicity, speed, and cost, they can help patients make informed decisions about the need to seek care and the infection risk they pose to others (Table 4).