Clinical Landscape of COVID-19 Testing: Difficult Choices
Darshan Gandhi, Sanskruti Landage, Joseph Bae, Sheshank Shankar, Rohan Sukumaran, Parth Patwa, Sethuraman T V, Priyanshi Katiyar, Shailesh Advani, Rohan Iyer, Sunaina Anand, Aryan Mahindra, Rachel Barbar, Abhishek Singh, Ramesh Raskar
CClinical Landscape of COVID-19 Testing: DifficultChoices
Darshan Gandhi ∗ , Sanskruti Landage ∗ , Joseph Bae ∗† , Sheshank Shankar ∗ , Rohan Sukumaran ∗ , Parth Patwa ∗ ,Sethuraman T V ∗ , Priyanshi Katiyar ∗ , Shailesh Advani ∗ , Rohan Iyer ∗ , Sunaina Anand ∗ , Aryan Mahindra ∗ , Rachel Barbar ‡ ,Abhishek Singh ‡ , Ramesh Raskar ∗‡∗ PathCheck Foundation , ‡ MIT Media Lab
Cambridge, MA, USA † Renaissance School of Medicine
Stony Brook, NY, USACorresponding Author: [email protected]
Abstract —The coronavirus disease 2019 (COVID-19) pandemichas spread rapidly across the world, leading to enormousamounts of human death and economic loss. Until definitivepreventive or curative measures are developed, policies regardingtesting, contact tracing, and quarantine remain the best publichealth tools for curbing viral spread. Testing is a crucial compo-nent of these efforts, enabling the identification and isolation ofinfected individuals. Differences in testing methodologies, timeframes, and outcomes can have an impact on their overallefficiency, usability and efficacy. In this early draft, we drawa comparison between the various types of diagnostic testsincluding PCR, antigen, and home tests in relation to theirrelative advantages, disadvantages, and use cases. We also lookinto alternative and unconventional methods. Further, we analyzethe short-term and long-term impacts of the virus and its testingon various verticals such as business, government laws, policies,and healthcare.
Index Terms —COVID-19, Testing, RT-PCR, Privacy, Quaran-tine, Sensitivity, Specificity, Molecular testing, Serological testing,Unconventional testing
I. I
NTRODUCTION
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as a novel type of coronavirus afterthe outbreak in the Wuhan region of China in late 2019.On March 11, 2020, the World Health Organization (WHO)declared COVID-19, the disease caused by this RNA virus,as a pandemic. COVID-19 is a disease with a relatively hightransmission rate, and is spread primarily by person-to-personcontact through respiratory droplets. As of November 5th2020, COVID-19 has led to more than 48 million cases and1 million deaths globally. Diagnosis of COVID-19 amongpatients involves testing through laboratory testing, clinicalexamination and diagnostics (X-ray, Chest-CT and others).Early positive test identification enables isolation of infectedpatients in order to reduce transmission [24]. Notably, a largegroup of individuals identified as infected with SARS-CoV-2 are asymptomatic. This suggests the necessity for frequenttesting of all individuals in a population, which in turn requiresmore cost efficient and rapid testing platforms . Presently, reverse transcription polymerase chain reaction(RT-PCR) assays are the most widely used method of COVID-19 detection. RT-PCR identifies the existence of viral RNA inbiological specimens from patients [19]. In RT-PCR testingthe most time-consuming steps are purification of RNA andreverse transcription. Because it detects viral RNA, RT-PCRis extremely sensitive and specific for SARS-CoV-2 infectiondetection. Rapid antigen tests are another common form oftesting in the setting of COVID-19, and detect viral proteins inpatient samples. These tests are much cheaper, faster, and moreconvenient than RT-PCR tests, but are generally less sensitive.Although less sensitive, antigen tests can be used to identifythe most infected patients in the affected region to control thespread of COVID-19 [37].In this early draft, our goal is to address the currentscenario of COVID-19 testing methodologies and summarizethe implementation, cost and production estimates, and finallyeffects on different sectors of society of these tests. Relevantrelated work in surveys, comparative studies and methodsto mitigate the COVID-19 crisis is discussed in the RelatedWork section. We then move to an in-depth discussion ofthe various current testing methods stratified by molecular,serological and alternative/unconventional approaches in theNative Methodologies in Clinical Testing section. We furtherdive deeper to understand the implications of testing and theimpacts it has on privacy, communication, the economy, etc.in the Effect of Testing section.II. R
ELATED W ORK
Fig 1 elaborates on temporal patterns of viral shedding in94 patients with laboratory-confirmed COVID-19 and modeledCOVID-19 infectiousness profiles from a separate sample of77 infector–infectee transmission pairs. They observed thehighest viral load in throat swabs at the time of symptomonset, and inferred that infectiousness peaked on or beforesymptom onset. The authors have estimated that 44% (95%confidence interval, 30–57%) of secondary cases were infectedduring the index cases’ presymptomatic stage, in settings a r X i v : . [ q - b i o . O T ] N ov igure 1. Symptom profiles and patient behaviours appropriate for variousCOVID-19 testing methodologies.Figure 2. Estimated serial interval distribution (top left), inferred infectious-ness profile (top right) and assumed incubation period (bottom middle) ofCOVID-19 (waiting for permission) [30] with substantial household clustering, active case finding andquarantine outside the home. Disease control measures shouldbe adjusted to account for probable substantial presymptomatictransmission [30].Tang Wi et al. discusses the current landscape of COVID-19 in different windows, namely pre-analytical, analytical,and post-analytical. The pre-analytical window discusses theimportance of collecting the right specimen at the right timein COVID-19 infection. The analytical window seeks to weighthe relative advantages of different testing approaches includ-ing RT-PCR and antigen tests. Finally the post-analytical land-scape discusses how tests might be understood with relevantmolecular or serological bottlenecks. Our paper aims to gofurther in providing a comprehensive analysis of both thevarious tests available as well as their relative advantagesin different use cases. We also discuss various secondaryand alternative testing methods in addition to serologicalapproaches [44].Mina et al. examines the current testing scenario to explainthe flaws in the current testing landscape. They primarily claimthat the more accurate RT-PCR tests used may be primarily Figure 3. Human to Human Transmission: Temporal dynamics in viralshedding and transmission of COVID-19 (waiting for permission) [30] detecting non-infectious individuals with low viral loads. Minaet al. also suggests that a low sensitivity test done at morefrequent intervals might be more efficient in understandingviral spread than limited, high sensitivity tests might be ableto do [36].Marac et al. does a comprehensive review on molecularand serological tests and also talks about the need to upscalein-vitro diagnostic assays. The paper also shows that thesedifferent tests could help inform healthcare providers andpolicy makers, especially in understanding the efficacy of testsand in making efficient policy decisions [34].Ngyun, T Thanha discusses the AI methods that are madeto understand and fight against the ongoing pandemic. Thepaper is a survey of methods in image analysis, text under-standing and information extraction, data analytics, IoT, etc..An overview of the relevant data sources and a description of13 sub groups of problems where AI and relevant methodscan potentially be useful are also presented [38].III. N
ATIVE M ETHODOLOGIES OF C LINICAL T ESTING
A. Need for Testing
Given that many people infected with COVID-19 continueto be asymptomatic and potential carriers of the virus, testingplays a crucial role in identifying these individuals to preventfurther spread through contact tracing and isolation. Testingcan be carried out to identify infected cases, most importantlyhelping to identify individuals who are infected and isolatethem. With the availability of numerous testing practices, thereare many methods with different analytical performances interms of sensitivity and specificity. Because viral load is oftencorrelated with the probability of a test, patients with an earlyinfection may often not be detected. After 3-4 days follow-ing infection, there is an exponential increase in viral load,generally seeming to result in symptom development. Thesecan range from mild infection to adverse and serious eventsnvolving lung disease, acute respiratory distress syndrome(ARDS), and other non-pulmonary manifestations.
B. Diagnostic Tests
Testing for SARS-CoV-2 can be largely classified intotwo broad categories: diagnostic testing attempts to identifyviral presence, whereas antibody/serological tests identify theimmune response generated to the virus [17].The gold standard method for diagnostic testing involvesthe use of reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR tests identify viral genomic material from hu-man samples typically taken from the nasopharyngeal cavity,throat, saliva, and so on. Specimens obtained from patientsmust therefore be sent to centralized laboratories for storageand testing [11], [29]. The results of these tests can be obtainedin a few hours after specimens arrive at the laboratory, butthe total turnaround time to patients is often between 3-7days. The test is highly sensitive and specific in nature and isgenerally the gold standard at the moment. Reliable methodsof evaluating the objective accuracy, sensitivity, and specificityof RT-PCR tests have not been developed, but it is assumedthat in ideal laboratory conditions these tests are able to detectSARS-CoV-2 genetic material with high degrees of sensitivityand specificity [33], [35], [41], [43].
Figure 4. Steps in the RT-PCR test: a) A patient specimen is obtained(commonly through nasopharyngeal swab) b) viral RNA is retrieved and c)reverse transcription is used to create complimentary DNA (cDNA). d) DNAprimers are then affixed to cDNA and are used for amplification. Fluorescenceis created following degradation of specialized DNA probes which increaseas copies of the viral cDNA are made. e) Once the detected fluorescence levelcrosses a threshold, a positive test is identified (waiting for permission) [18].
Rapid Antigen Detection Tests (RADT) is a rapid way oftesting to detect the presence or absence of SARS-CoV-2 ina point-of-care setting. These tests identify the presence ofvirus-specific proteins (antigens) in collected specimens frompatients. Specimens are generally collected from the same regions as those used for RT-PCR (nasopharyngeal, nasal,throat, etc), but testing can be done in a rapid manner and isoften done on-site rather than at specialized laboratories [25].Specimens are analyzed via immunological assays for viralparticles and can be done in many non-specialized laboratorysettings. Results for RADT can be obtained as quickly as30-60 minutes, but the sensitivity of these tests is generallylower than RT-PCR (84-97% when compared with RT-PCRresults). However, these tests are considered very specific (90-98% when compared with RT-PCR). Because of this, a patienttesting positive by RADT will generally be considered to beinfected with the virus whereas a patient testing negative maybe referred to an RT-PCR test if there is suspicion of infection.Due to their speed and cost-effectiveness, RADT can be usedin point-of-care settings (doctors, hospitals) and can also beused as a public health intervention for rapid detection andestimation of disease burden in a community setting.
Figure 5. Diagram briefly describing the function of medical diagnosticdipsticks (waiting for permission) [9].
Lateral flow assay (LFA) antigen tests are another exampleof rapid point-of-care testing. The test analyzes plasma, blood,or other patient samples and is capable of detecting viralantigen. These tests do not require laboratory analysis and canbe performed in any clinical setting. These tests have relativelylow sensitivities but are both fast and cost-effective. Due tothese reasons, these sometimes serve as an alternative and auseful tool in identifying the prevalence of COVID-19 spreadin a community [29].The RT-PCR test employs the amplification of smallamounts of viral RNA particles in patient specimens.
CycleThresholding (CT) [15] is the concept of amplifying the virus‘x’ number of times, where ‘x’ can be any number in orderto understand the viral concentration (viral load). Lower CTvalues mean that fewer amplification cycles were required todetect viral RNA, indicating that the patient sample had a highviral load. Alternatively, high CT Values indicate that the viralload is comparatively low and hence additional amplificationsare required for detection.There is no definite threshold forclearing the individual for the risk of spreading the virus.Some research has indicated that CT values can be correlatedto infectivity, with higher values indicating a lower chancethat a person might transmit COVID-19. CT values also differ igure 6. LFA Strip architecture where the analyte is detected in the test line,and red control line indicates the test was performed (waiting for permission)[28]. based on parameters such as age, gender, the prevalence ofcomorbidities, or concurrent infection [20].
Figure 7. Stages for RT-PCR Post Run Analysis (waiting for permission)[15].
Rethinking the Test Sensitivity : When considering therelative advantages and disadvantages of the various diagnosticCOVID-19 tests approved by the FDA for emergency use, it isimportant to understand the intended use case of the test. Minaet al. [36], suggests that low sensitivity, low price tests suchas LFA antigen tests might most effectively be used in publichealth scenarios in which the desired outcome is outbreaksuppression. By testing each individual in a community dailywith these tests, Mina et al., argues that patients with highviral loads (and therefore potentially higher infectivity) willbe immediately recognized by low sensitivity tests and canthen be quarantined to prevent disease spread. While this doesseem to be an attractive testing policy for reducing outbreaks, it relies on an increased understanding into the relationshipbetween viral load, infectivity, and symptom manifestationin the setting of COVID-19. Further, it is likely that thistesting paradigm would still need to be supplemented byhigher sensitivity testing in vulnerable populations where evenlow viral load COVID-19 infection could result in severeoutcomes.
Figure 8. Virus Kinetics within the Individual (waiting for permission) [36]
C. Antibody Tests
Antibody tests are done after recovery from COVID-19 tocheck whether a patient has developed immunity to COVID-19through measurements of IgM or IgG antibodies against thevirus. Antibodies are a physiological immune response againstSARS-CoV-2 infection, and their presence might indicate thatan individual has recently been infected with the virus or hasdeveloped long term immunity to the same. The informationprovided by antibody testing is highly variable from patientto patient and depends significantly on when the test wasacquired relative to infection with SARS-CoV-2. Antibodyresponses can take up to weeks to be detectable following viralinfection, and some patients might not have detectable levelsdespite a previous infection. Alternatively, there is evidencethat positive test results can be observed for patients withoutrecent SARS-CoV-2 infection due to the presence of antibodiesto similar viruses. These tests are not meant to be diagnosticin nature. Instead, antibody testing is often done to determinewhether an individual had previously been infected by SARS-CoV-2. This can be useful in the setting of determining eligibleplasma donors for COVID-19 treatments, or in other similarscenarios [4], [23], [33].
D. Current Scenario of Testing
Testing guidelines have varied over the course of theCOVID-19 pandemic, generally dependent on the availabilityof tests. Initially, testing supply shortages in the United Statesnecessitated strict rationing of testing kits to only those whoare sick and mandating that individuals be recommended bya physician in order to receive a test. Currently, the CDC rec-ommends that individuals with symptoms of infection, recent igure 9. Comparison between Native Testing MethodologiesFigure 10. Comparative Analysis Between Native Testing Methodologies contact with someone with COVID-19, or a recommendationfrom a healthcare provider be tested for infection with SARS-CoV-2. Additionally, workplaces require essential workers andother non-essential workers to have repeat COVID-19 testsbefore arriving at their workplace. Molecular tests includingRT-PCR are recommended for diagnosis of COVID-19, asthese are known to provide the most specific and sensitiveresults.Errors in testing can have dramatic effects. False-negativeresults might delay the quarantine of an individual, increasingthe likelihood of disease spread. False-positive results mightcause undue stress for a patient and cause loss of access toeconomic, social, and personal support in lieu of quarantine.It is important to note that comparative analysis between thevarious testing methodologies with respect to their accuracy,false negative rate and costing are not completely dependablesince there are many players in the market who manufacturethe testing kits to be used for the process and also the inherentdisparity that can be observed in the laboratory vs clinicalperformance of a test.Home test kits are a recent development and are becomingincreasingly prevalent. The majority of home tests collectsamples of either saliva (in a collection tube) or nasal swabs(through cotton swabs). Using these kits, an individual can shiptheir samples to testing labs directly from their house. Afterthe sample is received by the lab, results are typically deliveredwithin 48-72 hours [5]. Although these tests generally suffer from lower accuracies than RT-PCR, they are attractive due totheir convenience and relatively low price point.There remains a need to develop strict guidelines for socialdistancing and mobility including use of PPE and masks whenvisiting public places.
E. Activity-Feeling Guide
Getting tested is not a binary decision. There are manydecisions that need to be made for uninformed user-specificguidance, such as an Activity-Feeling Matrix, which is ahelpful tool. It is important to promote low friction home testsfor low-stakes situations and drive behavior to optimal risk-anxiety levels.For example, depending on the individual’s level of activity(i.e. work from home vs working in the community) level andfrequency of tests might vary in terms of intensity and followup. There can be an observed shift from the less accurate testssuch as home tests to the far more accurate ones like the RT-PCR if an individual wishes to attend social functions or hasa need for travel.
F. Assessment of Risks and Incident Prevention
Risk management is a highly understood field, and well-established strategies make use of multi-layer interventions inorder to prevent undesirable outcomes.
Figure 11. Swiss cheese model of process safety (waiting for permission)[12] his same approach can be adopted in the setting ofCOVID-19, in which multiple interventions can be simulta-neously leveraged to reduce disease spread. These strategiesmight include maintaining social distancing practices, employ-ing effective ventilation systems in buildings, wearing masks,washing and sanitizing hands at regular intervals, havingquicker and efficient testing procedures, and improved contacttracing procedures in order to quickly contain outbreaks of thedisease. Further, strict follow-up of individuals who are eitherquarantined due to positive test or exposed to a COVID-19positive individual remains crucial for successful reduction inthe burden of COVID-19.
Figure 12. Swiss Cheese Respiratory Virus Pandemic Defense (Swiss CheeseRespiratory Virus Pandemic Defense) (waiting for permission) [1]
IV. A
LTERNATIVE T ESTING M ETHODS
A. Introduction
It is integral to expand testing capabilities to manage thefurther spread of COVID-19. Along with this expansion, thereis a need for developing alternative strategies to identifyand isolate asymptomatic and presymptomatic individuals.Efficient pipelines for specimen collection and analysis arecrucial.A variety of factors must be considered when selecting aCOVID-19 test including cost, accuracy, availability, dissem-ination, and speed of testing results. Depending on the usecase, each of these factors might be weighted in a differentmanner. There is an increase in alternative testing methods asemergency use authorizations have been provided by the FDA,enabling multiple community-level testing strategies to controlCOVID-19.
B. Pool Testing
In pooled tests, several samples are mixed together in abatch in order to test specimens from multiple individualssimultaneously. This allows for greater testing capabilitieswithout using more resources. In this process there is anincreased chance of positive sample dilution, potentially de-creasing test sensitivity. According to FDA guidelines, testperformance following the pooling of samples should have apositive predictive agreement (PPA) of greater than 85% whencompared with tests run on individual samples [14]. This type of testing substantially reduces the costs of testing and is afaster method for testing multiple individuals. This enablesestimations of COVID-19 prevalence in group settings such asinstitutions or communities. The ideal use case for these testsis in the setting of relatively sparse COVID-19 positivity/lowprevalence [11], [46].
C. Wastewater Testing
Experiences with other viral diseases have shown that mon-itoring wastewater enables effective surveillance of COVID-19 by tracing pathogen levels in sewage. This can effectivelyshow the presence of pathogens in an entire community,providing a sensitive signal to detect whether the transmissionis increasing or declining.Wastewater testing could have many benefits with regardsto the detection of COVID-19 as it is cost-effective to surveythe dynamics of communities. Other forms of epidemiologicalindicator biases are effectively avoided and it enables thecollection of data even from people who don’t have accessto healthcare.After excretion in feces, the virus collects in municipalwastewater channels. Monitoring of this wastewater at treat-ment plants can be achieved by detecting viral RNA.V. U
NCONVENTIONAL T ESTING M ETHODOLOGIES
A. COVID-19 and Animals
In most research works related to healthcare and medicineanimals are very essential segment of the cycle, especiallyin zoonotic viruses such as SARS-CoV-2. However, thoroughtesting on animals has not been performed yet; only a fewspecies (such as ferrets, dogs, birds, cats, hamsters and minks)have shown to be susceptible to the virus. Preliminary researchhas shown high interspecies transmission rates in ferrets,cats, and golden hamsters, but significantly lower rates indogs. Furthermore, animals such as ducks, chickens, miceand pigs do not seem to be able to contract or transmitthe virus [3]. Further experiments can be performed in thesespecies to understand the mechanisms by which other animalsmight recover from infection, potentially informing treatmentdevelopment for humans [6].
B. Reverse transcription loop-mediated isothermal amplifica-tion (RT-LAMP)
Researchers from the Journal of Science TranslationalMedicine proposed the use of a technique called reverse tran-scription loop-mediated isothermal amplification (RT-LAMP)[27] carried out at a constant temperature with a different set ofreagents than those used in RT-PCR. Here, simple equipmentlike plate scanners with spectrophotometric quantification,mobile phone cameras, copy machines, or office scanners canbe used for immunofluorescent detection. Expensive specialequipment such as thermal cyclers with real-time fluorescencemeasurements is not required for an RT-LAMP assay to per-form, because within 30 minutes after the start of incubation(at 65°C), positive samples can be determined by a colorchange from red to yellow [29], [33].his testing is less sensitive than a quantitative RT-PCR,however, it could be beneficial in the testing of large groupsof people because of its potential to be a simple, scalable, andbroadly applicable testing method.
C. SalivaDirect
SalivaDirect is a testing method that relies on a similarmolecular process as RT-PCR. Compared to RT-PCR, thismethod is less expensive and places less stress on the sup-ply chain. In addition, RT-PCR requires a trained personto collect nasopharyngeal (NP) swabs, not only adding alogistical barrier, but also putting the performer at risk ofgetting infected. Saliva samples are easier to collect and lessuncomfortable, encouraging people to get tested frequently.However, saliva tests were found to have lower sensitivity thana nasopharyngeal swab test [26].
D. LamPORE
LamPORE combines barcoded multi-target amplification,real-time nanopore sequencing, and 15-minute barcode librarypreparation [31]. It enables a larger number of samples to berapidly tested/screened for the presence or absence of SARS-CoV-2, the virus causing COVID-19. Starting with extractedRNA, results for 12-96 samples can be obtained in less than2 hours [27].This method not only fits both large-scale and small-scalelaboratory environments, but can also potentially analyze thou-sands of samples daily using a single instrument. LamPOREis dependent on up-to-date workflow, including automatic han-dling of all samples and an amalgamation with the informationmanagement systems of the laboratory.VI. E
FFECT OF THE T ESTINGS
A. Quarantine
Generally, an individual takes a COVID-19 test because theyare either showing symptoms of the virus, or due to mandatedworkspace regulations. Until test results are received, the indi-vidual must stay isolated. If an individual receives a negativeresult from a lower sensitivity point-of-care or home test, itis recommended that they seek another negative result viaRT-PCR if infection is still suspected. During quarantine, thepatient should keep away from others, wear a face covering,follow strict hand-hygiene, and make an effort to utilizedifferent utensils, instruments and tools from other membersof his/her household [24].In case of an emergent need for the patient to breakquarantine, they should maintain at least 6 feet distance fromothers. In addition, caretakers and family members exposed toan individual with COVID-19 should follow similar guidelines(including testing, quarantine, and preventive techniques).
B. Privacy
COVID-19 testing practices involve the collection and dis-tribution of a significant amount of personal information. Oftenan individual’s name, race, location, travel history, and pasthealth records are collected. This dependence on sensitive patient data provides many potential privacy concerns relatedto COVID-19 testing. For example:1) To schedule a test, a user has to share their name, email,phone number, ethnicity, country of birth, and recenttravel history. Although it differs based on the testingsite and country, this personally identifiable informationoften sits on web servers or in handwritten forms attesting campsites.2) Some private testing companies collect extensive userinformation about the user despite its irrelevance toCOVID-19 testing. This can vary significantly betweentesting sites and countries. The use of anonymous ran-domized identifiers can reduce these risks.3) Contact tracing is the single public health interventionthat has been most effective in identifying potentially in-fected individuals. These efforts often neglect thoroughsafeguards of individual privacy.4) COVID-19 results are often conveyed to users on web-sites that require no more than name and birthdate tolook up the results, an obvious privacy concern.The privacy breaches outlined above can form the basis formore significant invasions of patient privacy [25], allowingdisingenuous parties to track patient schedules, economicstatus, and social contacts. The potential misuse of this infor-mation can dramatically impact patient safety and well-being.
C. Communication
Testing and contact tracing remains crucial to the publichealth workforce around the world in identifying, assessing,and managing individuals to contain the spread of COVID-19. But for many people, coming forward to get tested andrevealing the personal information of friends, family, and closeassociates remains a challenge due to privacy reasons. TheCOVID-19 upsurge has given rise to discriminatory behaviorstowards anyone discerned to have been in contact with thevirus [24]. This social stigma discourages individuals fromreceiving COVID-19 tests, adding another layer of complexityto public health policies and data collection efforts surroundingthe pandemic.
D. Economy
The impact of COVID-19 on the economy has been sig-nificant. Due to COVID-19, several small and large-scalebusinesses have been negatively affected. The virulent andrapid spread of COVID-19 has required many organizationsto change their work and marketing strategies. Small casebusinesses have been most significantly affected [22]. 43%of businesses were temporarily shut down in earlier stagesof the pandemic, and the employment rate dropped downby 40% in the United States. This has raised questionsabout the financial stability of small businesses as many haveneeded to acquire additional debts, temporarily cut downor furlough their workforce, and ultimately shut down inmany cases. A recent analysis [7] has provided 3 potentialfuture economic scenarios in the setting of COVID-19: globaleconomic slowdown, global recession, or a quick reformationf the economy. The last relies upon the implementation ofpublic policies including widespread testing, mandated facecoverings, social distancing, and new sanitization standardsin order to facilitate a return to normalcy for the economy. Inscenarios in which transmission of the virus cannot be curbed,economic slowdowns and recessions are far more likely.VII. F
UTURE POSSIBILITIES FOR T ESTING
Researchers are in the preliminary phases of exploringmultiple novel methods, focused on improving the accuracy,speed, cost and complexity of COVID-19 tests. One such ini-tiative based on various biological innovations is STOPCovid[32], working to offer rapid at-home tests with simpler kits.Researchers are also exploring testing methods that leveragemachine learning to detect COVID-19 from signals such ascough noises, lung and respiratory performance, and vocalcord strength [38]. These methods have the potential to sub-stantially simplify the testing process, allowing for increasedaccessibility and mass population testing.VIII. D
ISCUSSION AND C ONCLUSION
As the COVID-19 pandemic continues to rapidly grow inthe United States and across the world, new testing method-ologies will continually be developed. In this early draft, wepresent a detailed review of the clinical landscape of COVID-19 testing and establish the metrics by which future tests mightbe measured and understood. Test sensitivity is only one factorthat must be considered in combination with a test’s cost,speed, diagnostic potential,Using this framework, we describe the current mainlinediagnostic and serological testing methodologies available aswell as their relative advantages and use cases. Further, weextend our analysis to novel, unconventional, and alternativemethods of testing, which could reduce the time and costinvolved to obtain results.We also discuss the potential privacy concerns relevantto current testing approaches. Given the tradeoffs betweenbenefits vs harms of testing, the landscape remains open tonew testing strategies, especially those that minimize the riskto an individual’s privacy. New testing methods and tools, suchas STOPCovid and Cosware, might be used to supplementcurrent COVID-19 testing strategies while maintaining userprivacy. A
CKNOWLEDGEMENTS
We are grateful to Riyanka Roy Choudhury, CodeX Fel-low, Stanford University, Adam Berrey, CEO of PathCheckFoundation, Dr. Brooke Struck, Research Director at TheDecision Lab, Canada and Vinay Gidwaney, Entrepreneurand Advisor, PathCheck Foundation for their assistance indiscussions, support and guidance in writing of this paper.R
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