LitCovid-sentences  

PMC:7170415 / 1962-28855 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T17 0-18 Sentence denotes Key Summary Points
T18 19-128 Sentence denotes The COVID-19 pandemic demonstrates the essential role of diagnostics in the control of communicable diseases.
T19 129-351 Sentence denotes Laboratory-based molecular assays for detecting SARS–CoV-2 in respiratory specimens are the current reference standard for COVID-19 diagnosis, but point-of-care technologies and serologic immunoassays are rapidly emerging.
T20 352-467 Sentence denotes Early, massive deployment of SARS–CoV-2 diagnostics for case finding helped curb the epidemic in several countries.
T21 468-578 Sentence denotes Urgent clinical and public health needs now drive an unprecedented global effort to increase testing capacity.
T22 580-685 Sentence denotes In December 2019, a cluster of patients with pneumonia of unknown cause was reported in Wuhan, China (1).
T23 686-848 Sentence denotes The causative pathogen was subsequently identified as severe acute respiratory syndrome–related coronavirus-2 (SARS–CoV-2) (2), a newly described betacoronavirus.
T24 849-974 Sentence denotes This virus, now recognized as the etiologic agent of COVID-19 disease, is the seventh known coronavirus to infect humans (1).
T25 975-1078 Sentence denotes Since the recognition of COVID-19, there has been an exponential rise in the number of cases worldwide.
T26 1079-1216 Sentence denotes As of 1 April 2020, the World Health Organization reported more than 926 000 cases in more than 195 countries, areas, or territories (3).
T27 1217-1505 Sentence denotes Reasons for the rapid spread include high transmissibility of the virus (4, 5), especially among asymptomatic or minimally symptomatic carriers (6, 7); the apparent absence of any cross-protective immunity from related viral infections; and delayed public health response measures (8–10).
T28 1506-1614 Sentence denotes Age and the presence of comorbid illnesses increase the risk for death among persons with COVID-19 (11, 12).
T29 1615-1786 Sentence denotes The clinical manifestations of COVID-19 in children are less severe compared with adults, yet age younger than 1 year seems to increase the risk for critical illness (13).
T30 1787-1958 Sentence denotes Current case-fatality rate estimates range from 0.6% to 7.2% by region and seem to be substantially higher than the 0.1% mortality rate of seasonal influenza (12, 14, 15).
T31 1959-2164 Sentence denotes However, current estimates of COVID-19 case-fatality rates are probably inflated because of preferential testing in many countries of persons with severe manifestations, who are at risk for death (12, 16).
T32 2165-2322 Sentence denotes In Germany and South Korea, the case-fatality rates are less than 0.5%, probably because extensive testing revealed a large denominator of mild illness (17).
T33 2323-2490 Sentence denotes It has been estimated that before the wide-scale travel restrictions in China, undiagnosed SARS–CoV-2 represented the infection source for 79% of documented cases (7).
T34 2491-2600 Sentence denotes These observations underscore the critical importance of ample, accurate diagnostic testing in this pandemic.
T35 2601-2739 Sentence denotes Here, we review the current array of tests for SARS–CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.
T36 2741-2748 Sentence denotes Methods
T37 2749-2824 Sentence denotes We searched the PubMed database for articles on SARS–CoV-2 and diagnostics.
T38 2825-3451 Sentence denotes The Medical Subject Headings (MeSH) search terms used were “Coronavirus”[MeSH]; “Coronavirus Infections”[MeSH]; “Severe Acute Respiratory Syndrome”[MeSH]; “Betacoronavirus”[MeSH]; “SARS Virus”[MeSH]; “Polymerase Chain Reaction”[MeSH]; “Reverse Transcriptase Polymerase Chain Reaction”[MeSH]; “High-Throughput Nucleotide Sequencing”[MeSH]; “Sensitivity and Specificity”[MeSH]; “Point-of-Care Testing”[MeSH]; “Antigens”[MeSH]; “Serology”[MeSH]; “Immunoglobulin G”[MeSH]; “Immunoglobulin M”[MeSH]; “Clustered Regularly Interspaced Short Palindromic Repeats”[MeSH]; “CRISPR-Cas Systems”[MESH]; and “Diagnosis, Differential”[MESH].
T39 3452-3667 Sentence denotes Non-MeSH search terms used were covid, SARS, SARS-CoV, pcr, digital droplet PCR, next generation sequencing, point-of-care test, antigen, analyte, serology, Immunoglobulin, CRISPR-CAS, Diagnos, and turn around time.
T40 3668-3766 Sentence denotes Only articles including human subjects and those published from 2003 to the present were included.
T41 3767-3832 Sentence denotes Articles in languages other than English or French were excluded.
T42 3833-3904 Sentence denotes We screened the results on title and abstract for relevant information.
T43 3905-4089 Sentence denotes Starting from the articles found in this search, we used a snowball search strategy, scanning useful references and similar articles and retrieving those that were considered relevant.
T44 4090-4152 Sentence denotes Furthermore, experts were consulted for additional literature.
T45 4153-4239 Sentence denotes Guidelines and resources from international organizations were used where appropriate.
T46 4240-4285 Sentence denotes This search was last updated on 1 April 2020.
T47 4287-4344 Sentence denotes The Role of Diagnostic Testing in the SARS–CoV-2 Pandemic
T48 4345-4534 Sentence denotes The primary goal of epidemic containment is to reduce disease transmission by reducing the number of susceptible persons in the population or by reducing the basic reproductive number (R0).
T49 4535-4716 Sentence denotes This number is modulated by such factors as the duration of viral shedding, the infectiousness of the organism, and the contact matrix between infected and susceptible persons (18).
T50 4717-4897 Sentence denotes Given the lack of effective vaccines or treatments (19), the only currently available lever to reduce SARS–CoV-2 transmission is to identify and isolate persons who are contagious.
T51 4898-4966 Sentence denotes Deployment of SARS–CoV-2 testing has varied widely across the globe.
T52 4967-5088 Sentence denotes A few Asian countries have illustrated the power of preparedness, flexible isolation systems, and intensive case finding.
T53 5089-5187 Sentence denotes South Korea dramatically slowed the epidemic by implementing an unprecedented testing effort (20).
T54 5188-5356 Sentence denotes Using innovative measures, South Korea performed more than 300 000 tests (5828.6 tests per million persons) in the 9 weeks after the first case was identified (20, 21).
T55 5357-5444 Sentence denotes Singapore used a broad case definition, aggressive contact tracing, and isolation (10).
T56 5445-5719 Sentence denotes Moreover, to identify infected persons not meeting the case definition, Singapore screened patients with pneumonia and influenza-like illnesses in hospitals and primary care settings, severely ill patients in intensive care, and deaths with a possible infectious cause (10).
T57 5720-5770 Sentence denotes Taiwan and Hong Kong used similar approaches (22).
T58 5771-5919 Sentence denotes These countries rapidly deployed resource-intensive strategies that prioritized aggressive testing and isolation to interrupt transmission (20, 22).
T59 5920-6102 Sentence denotes In the face of widespread transmission, the role of diagnostic testing is contingent on the type of testing available, the resources required for testing, and time to obtain results.
T60 6103-6326 Sentence denotes For example, rapidly identifying cases among hospitalized patients remains a high priority to properly allocate personal protective equipment and to prevent nosocomial spread with subsequent community transmission (23, 24).
T61 6327-6433 Sentence denotes Likewise, specific treatment decisions and enrollment in ongoing clinical trials require prompt diagnosis.
T62 6435-6454 Sentence denotes Diagnostic Testing:
T63 6455-6477 Sentence denotes Defining Key Use Cases
T64 6478-6672 Sentence denotes Despite the remarkable speed with which accurate diagnostic tests have been developed and made available for SARS–CoV-2 (25), current tools only partially meet several clinically relevant needs.
T65 6673-6787 Sentence denotes Figure 1 illustrates different indications for diagnostic testing among persons with proven or suspected COVID-19.
T66 6788-6899 Sentence denotes For each of these, the most important consideration is the clinical decision a test result will help to inform.
T67 6900-7367 Sentence denotes Test designs must account for several parameters, such as whether the test detects infection directly (such as the virus itself) or indirectly (such as host antibodies), test turnaround time, the ability to perform many tests at the same time (that is, throughput), the need to have a minimum number of specimens before testing (that is, batching), and the ability to perform the test in low-infrastructure settings (such as on cruise ships or in remote communities).
T68 7368-7438 Sentence denotes The potential for use at the point of care depends on test complexity.
T69 7439-7447 Sentence denotes The U.S.
T70 7448-7532 Sentence denotes Food and Drug Administration (FDA) categorizes diagnostic tests by their complexity:
T71 7533-7668 Sentence denotes Waived tests are available for use at the point of care, whereas moderate- and high-complexity tests must be performed in a laboratory.
T72 7669-7745 Sentence denotes The intended use also determines which specimen types are ideal or feasible.
T73 7746-7865 Sentence denotes Finally, it is important to recognize that the acceptable diagnostic accuracy of a test may vary according to use case.
T74 7866-8135 Sentence denotes For example, sensitivity and specificity requirements of an assay used to confirm results of a screening test need not be as stringent as those of a method used for standalone diagnosis, because the pool of persons being tested is already enriched with true infections.
T75 8136-8298 Sentence denotes The Foundation for Innovative New Diagnostics has published a detailed assessment of priority use cases to be considered by test developers and policymakers (26).
T76 8299-8308 Sentence denotes Figure 1.
T77 8310-8403 Sentence denotes Examples of use cases for diagnostic testing among persons with proven or suspected COVID-19.
T78 8404-8616 Sentence denotes A test well suited for one use case (such as epidemiologic surveillance) may be completely inadequate for another (such as rapid screening of symptomatic patients for allocation of personal protective equipment).
T79 8617-8852 Sentence denotes For test results to enable a specific clinical decision, test developers, policymakers, and clinicians need to consider each of these with respect to the intention of testing and the population being tested as specifically as possible.
T80 8853-9140 Sentence denotes For the moment, most use cases placed above the green and gray bar are best met by nucleic acid amplification tests, whereas detection of host-derived antibodies directed against SARS–CoV-2 will be crucial for surveillance, epidemic forecasting, and determination of SARS–CoV-2 immunity.
T81 9141-9210 Sentence denotes SARS–CoV-2 = severe acute respiratory syndrome–related coronavirus-2.
T82 9212-9224 Sentence denotes Who to Test:
T83 9225-9280 Sentence denotes Current Diagnostic Recommendations in the United States
T84 9281-9486 Sentence denotes In response to the rapidly evolving COVID-19 pandemic, countries have used different testing approaches depending on testing capacity, public health resources, and the spread of the virus in the community.
T85 9487-9663 Sentence denotes In the United States, diagnostic testing indications and capacity were limited at the beginning of the outbreak, largely because of regulatory hurdles for the use of new tests.
T86 9664-9800 Sentence denotes To expand access to testing, the FDA released policies to allow laboratories to use their validated assays in a more timely manner (27).
T87 9801-10005 Sentence denotes On 4 March, the Centers for Disease Control and Prevention (CDC) removed restrictive testing criteria, recommending that clinicians use their judgment to determine whether a test should be performed (28).
T88 10006-10118 Sentence denotes Because testing capacity remains suboptimal (27), the implementation of this recommendation remains a challenge.
T89 10119-10464 Sentence denotes The CDC still recommends priority for testing 3 groups: hospitalized patients with presentations compatible with COVID-19, other symptomatic persons at risk for poor outcomes, and persons who had close contact with someone with suspected or confirmed COVID-19 within 14 days of illness onset or have a history of travel in an affected area (28).
T90 10465-10553 Sentence denotes These patients should be evaluated with a molecular diagnostic test, as described later.
T91 10554-10610 Sentence denotes The CDC does not recommend testing asymptomatic persons.
T92 10612-10624 Sentence denotes How to Test:
T93 10625-10668 Sentence denotes Diagnostic Tests in Use or Under Evaluation
T94 10669-10952 Sentence denotes Although real-time reverse transcriptase polymerase chain reaction (RT-PCR)–based assays performed in the laboratory on respiratory specimens are the cornerstone of COVID-19 diagnostic testing, several novel or complementary diagnostic methods are being developed and evaluated (16).
T95 10953-11062 Sentence denotes Figure 2 depicts the adequacy of the principal assay types used or proposed for COVID-19 for 4 key use cases.
T96 11063-11221 Sentence denotes Among patients diagnosed with COVID-19, the occurrence of concomitant viral infections has been reported to range from below 6% (29) to greater than 60% (30).
T97 11222-11336 Sentence denotes As a result, it is not possible to rule out SARS–CoV-2 infection merely by detecting another respiratory pathogen.
T98 11337-11346 Sentence denotes Figure 2.
T99 11348-11430 Sentence denotes Heat map showing the adequacy of principal assay types (rows) for 4 key use cases.
T100 11431-11540 Sentence denotes * This assumes that assays in development or currently undergoing regulatory evaluation prove to be accurate.
T101 11541-11736 Sentence denotes † The utility of antibody detection assays for diagnosing acute infections is probably very limited around the time of symptom onset, when viral shedding and transmission risk seem to be highest.
T102 11737-11876 Sentence denotes Thus, although such tests may have a role among persons presenting late in the course of their infection, the potential for misuse is high.
T103 11878-11912 Sentence denotes Laboratory-Based Molecular Testing
T104 11913-12147 Sentence denotes The current diagnostic strategy recommended by the CDC to identify patients with COVID-19 is to test samples taken from the respiratory tract to assess for the presence of 1 or several nucleic acid targets specific to SARS–CoV-2 (25).
T105 12148-12322 Sentence denotes A nasopharyngeal specimen is the preferred choice for swab-based SARS–CoV-2 testing, but oropharyngeal, mid-turbinate, or anterior nares samples also are acceptable (31, 32).
T106 12323-12448 Sentence denotes Samples should be obtained by using a flocked swab, if available, to enhance the collection and release of cellular material.
T107 12449-12503 Sentence denotes Swabs with an aluminum or plastic shaft are preferred.
T108 12504-12637 Sentence denotes Swabs that contain calcium alginate, wood, or cotton should be avoided, because they may contain substances that inhibit PCR testing.
T109 12638-12774 Sentence denotes Ideally, swabs should be transferred into universal transport medium immediately after sample collection to preserve viral nucleic acid.
T110 12775-13003 Sentence denotes Samples taken from sputum, endotracheal aspirates, and bronchoalveolar lavage also may be sent directly to the microbiology laboratory for processing, and may have greater sensitivity than upper respiratory tract specimens (33).
T111 13004-13069 Sentence denotes Inadequate sample collection may result in a false-negative test.
T112 13070-13180 Sentence denotes After specimen collection, samples undergo RNA extraction followed by qualitative RT-PCR for target detection.
T113 13181-13263 Sentence denotes In the United States, the CDC has developed the most widely used SARS–CoV-2 assay.
T114 13264-13436 Sentence denotes The kit contains PCR primer–probe sets for 2 regions of the viral nucleocapsid gene (N1 and N2), and for the human RNase P gene to ensure the RNA extraction was successful.
T115 13437-13602 Sentence denotes This assay differs from the World Health Organization primer–probe sets, which target the SARS–CoV-2 RNA-dependent RNA polymerase (RdRP) and envelope (E) genes (25).
T116 13603-13836 Sentence denotes Both assays have high analytic sensitivity and specificity for SARS–CoV-2, with minimal cross-reactivity with other circulating strains of coronaviruses, and both use a cycle threshold of less than 40 as the criterion for positivity.
T117 13837-14120 Sentence denotes The CDC kit may be used by state public health laboratories, other laboratories determined by the state to be qualified, and clinical laboratories that meet the regulatory requirements of the Clinical Laboratories Improvement Amendment (CLIA) to perform high-complexity testing (27).
T118 14121-14255 Sentence denotes Dozens of laboratories have applied for Emergency Use Authorization (EUA) from the FDA for their own laboratory-developed assays (34).
T119 14256-14410 Sentence denotes The FDA also has granted an EUA for several commercial assays (35), further expanding the ability of clinical laboratories to use these platforms (Table).
T120 14411-14417 Sentence denotes Table.
T121 14418-14818 Sentence denotes The 28 Commercial SARS–CoV-2 in Vitro Diagnostic Assays Given an EUA From the FDA as of 4 April 2020 The lack of an established reference standard, use of differing sample collection and preparation methods, and an incomplete understanding of viral dynamics across the time course of infection hamper rigorous assessment of the diagnostic accuracy of the many newly introduced SARS–CoV-2 assays (36).
T122 14819-14932 Sentence denotes Serum and urine are usually negative for the presence of viral nucleic acid, regardless of illness severity (33).
T123 14933-15094 Sentence denotes Of importance, the ability of RT-PCR assays to rule out COVID-19 on the basis of upper respiratory tract samples obtained at a single time point remains unclear.
T124 15095-15343 Sentence denotes Conversely, after a patient has had a positive test result, several authorities have recommended obtaining at least 2 negative upper respiratory tract samples, collected at intervals of 24 hours or longer, to document SARS–CoV-2 clearance (37, 38).
T125 15345-15380 Sentence denotes Point-of-Care Molecular Diagnostics
T126 15381-15772 Sentence denotes Low-complexity, rapid (results within 1 hour) molecular diagnostic tests for respiratory viral infections that are CLIA waived (FDA approved for use outside the laboratory by nonlaboratory personnel) include cartridge-based assays on platforms that include the Abbott ID NOW (Abbott Laboratories), BioFire FilmArray (bioMérieux), cobas Liat (Roche Diagnostics), and GeneXpert (Cepheid) (39).
T127 15773-15893 Sentence denotes Rapid point-of-care assays for SARS–CoV-2 on instruments such as these will be critical to expand point-of-care testing.
T128 15894-16115 Sentence denotes The Xpert Xpress SARS–CoV-2 test (Cepheid) has received an FDA EUA and is performed on the GeneXpert platform, which is already widely used for tuberculosis and HIV testing, especially in low- and middle-income countries.
T129 16116-16333 Sentence denotes This capacity might be useful to scale up testing across the world as well as in settings where rapid results at the point of care would enable clinical decisions, although testing throughput may be a limiting factor.
T130 16335-16358 Sentence denotes Antigen Detection Tests
T131 16359-16615 Sentence denotes Tests that detect respiratory syncytial virus or influenza virus antigens by immunoassay directly from clinical specimens have been commercially available for decades, are of low complexity, and may provide results within minutes at the point of care (40).
T132 16616-16882 Sentence denotes Current tools for influenza and respiratory syncytial virus suffer from suboptimal sensitivity to rule out disease (41, 42); the same challenge would probably exist for SARS–CoV-2, and tests would need to be implemented with clear guidance on correct interpretation.
T133 16883-17016 Sentence denotes Prototypes of such tests for other novel coronaviruses have not received regulatory approval (43, 44) but are under development (45).
T134 17017-17180 Sentence denotes Monoclonal antibodies against the nucleocapsid protein of SARS–CoV-2 have been generated, which might form the basis of a future rapid antigen detection test (20).
T135 17182-17190 Sentence denotes Serology
T136 17191-17485 Sentence denotes Serologic tests that identify antibodies (such as IgA, IgM, and IgG) to SARS–CoV-2 from clinical specimens (such as blood or saliva), such as enzyme-linked immunosorbent assays, may be less complex than molecular tests and have the potential to be used for diagnosis in certain situations (46).
T137 17486-17661 Sentence denotes However, their utility for diagnosing acute infections is probably limited around the time of symptom onset, when viral shedding and transmission risk seem to be highest (32).
T138 17662-17744 Sentence denotes Antibody responses to infection take days to weeks to be reliably detectable (46).
T139 17745-17861 Sentence denotes Negative results would not exclude SARS–CoV-2 infection, particularly among those with recent exposure to the virus.
T140 17862-18067 Sentence denotes Cross-reactivity of antibody to non–SARS–CoV-2 coronavirus proteins is also a potential problem, whereby positive results may be the result of past or present infection with other human coronaviruses (47).
T141 18068-18280 Sentence denotes Serologic assays might be more relevant in scenarios in which patients present to medical care with late complications of disease, when RT-PCR may be falsely negative, because viral shedding drops over time (48).
T142 18281-18526 Sentence denotes The development of serologic assays that accurately assess prior infection and immunity to SARS–CoV-2 will be essential for epidemiologic studies, ongoing surveillance, vaccine studies, and potentially for risk assessment of health care workers.
T143 18527-18648 Sentence denotes Immunoassays are already on the market in some countries, but their diagnostic accuracy and optimal use remain undefined.
T144 18650-18676 Sentence denotes Ancillary Diagnostic Tests
T145 18677-18781 Sentence denotes The optimal use of diagnostic imaging, biomarkers, and other nonmicrobiologic tests is rapidly evolving.
T146 18783-18801 Sentence denotes Radiographic Tests
T147 18802-18873 Sentence denotes Many centers have evaluated the utility of chest imaging for diagnosis.
T148 18874-19031 Sentence denotes On chest radiography, bilateral pneumonia is the most frequently reported feature (range, 11.8% to 100%) and is more common than a unilateral focus (49, 50).
T149 19032-19200 Sentence denotes Computed tomography is regarded as more sensitive than radiography, with several cohort studies reporting that most patients (77.8% to 100%) had ground glass opacities.
T150 19201-19367 Sentence denotes Other features commonly reported with COVID-19 on chest computed tomography include a peripheral distribution, fine reticular opacities, and vascular thickening (51).
T151 19368-19544 Sentence denotes Compared with serial nasopharyngeal sampling, chest computed tomography may be more sensitive than an RT-PCR test at a single time point for the diagnosis of COVID-19 (52, 53).
T152 19545-19677 Sentence denotes In addition, artificial intelligence may help distinguish COVID-19 from other etiologic agents of community-acquired pneumonia (54).
T153 19678-19809 Sentence denotes However, these findings are not completely specific to COVID-19 and do not exclude a co-infection or an alternative diagnosis (55).
T154 19811-19855 Sentence denotes Biomarkers Associated With COVID-19 Patients
T155 19856-20166 Sentence denotes The most common laboratory features reported in patients with COVID-19 include decreased albumin (75.8% [95% CI, 30.5% to 100%]), elevated C-reactive protein (58.3% [CI, 21.8% to 94.7%]), and elevated lactate dehydrogenase levels (57.0% [CI, 38.0% to 76.0%]), and lymphopenia (43.1% [CI, 18.9% to 67.3%]) (56).
T156 20167-20432 Sentence denotes Other biomarkers that have been reported include increased erythrocyte sedimentation rates; elevated aspartate aminotransferase, alanine aminotransferase, and creatinine kinase levels; leukopenia; leukocytosis; and increased bilirubin and creatinine levels (57–59).
T157 20433-20643 Sentence denotes Such findings are not surprising, because these biomarkers represent an inflammatory host response to SARS–CoV-2 or are early markers of end-organ dysfunction, similar to that seen in patients with sepsis (60).
T158 20644-20826 Sentence denotes No biomarker or combination of biomarkers currently exists that is sensitive or specific enough to establish a diagnosis of COVID-19, or to pragmatically predict its clinical course.
T159 20828-20872 Sentence denotes Unmet Needs and the Diagnostic Test Pipeline
T160 20874-20913 Sentence denotes Scaling Up Access to Diagnostic Testing
T161 20914-21078 Sentence denotes In the face of a public health emergency, important first steps to expand testing capacity include relaxing and streamlining regulatory requirements and procedures.
T162 21079-21306 Sentence denotes Local public health laboratories and academic diagnostic laboratories in the United States are being rapidly enabled to perform EUA-granted commercial assays and laboratory-developed tests using research use–only reagents (61).
T163 21307-21476 Sentence denotes University research laboratories could also add capacity, although concerns exist regarding quality control and the absence of protocols for managing clinical specimens.
T164 21477-21611 Sentence denotes Flexibility regarding nucleic acid extraction methods and amplification instruments when using CDC protocols is being introduced (34).
T165 21612-21770 Sentence denotes National agencies are expeditiously making materials for test development and validation available to clinical laboratories and diagnostic test manufacturers.
T166 21771-21939 Sentence denotes Safely evaluating clinically stable persons for COVID-19 at traditional health care access points is resource intensive and slow, and risks exposing staff to infection.
T167 21940-22170 Sentence denotes Many jurisdictions are enabling innovative testing venues, such as external tents or drive-through or “phone booth” testing, as well as home assessment teams to expedite specimen collection while limiting potential exposures (62).
T168 22171-22258 Sentence denotes Telemedicine combined with at-home nasal swab self-testing also has been proposed (63).
T169 22259-22450 Sentence denotes Of importance, in jurisdictions without universal health care coverage, policy solutions must be introduced to eliminate financial barriers to testing for uninsured and underinsured patients.
T170 22451-22628 Sentence denotes Efforts to increase accessibility of testing for multiple use cases need to be coupled to appropriate public health interventions to isolate infected persons and their contacts.
T171 22630-22707 Sentence denotes Alternatives to Usual Specimen Types, Collection Devices, and Transport Media
T172 22708-22781 Sentence denotes Nasopharyngeal swabs are the recommended specimen for molecular analysis.
T173 22782-22959 Sentence denotes The sudden demand for flocked nasopharyngeal swabs and viral transport medium generated by the pandemic has put enormous pressures on supply chain capacities for these products.
T174 22960-23112 Sentence denotes As of 19 March 2020 the CDC made oropharyngeal, mid-turbinate, and nasal swabs acceptable specimen types if nasopharyngeal swabs are not available (31).
T175 23113-23292 Sentence denotes Early-morning posterior oropharyngeal saliva samples (coughed up by clearing the throat) also have been assessed as useful specimen types and would not require use of a swab (48).
T176 23293-23560 Sentence denotes The CDC has released a standard operating procedure for laboratories to create their own viral transport medium (64); other solutions also may be used if viral transport medium is unavailable, including phosphate-buffered saline, liquid Amies, and normal saline (65).
T177 23561-23700 Sentence denotes The FDA has provided guidance on its Web site for alternative materials to collect and transport samples for RT-PCR SARS–CoV-2 assays (34).
T178 23701-23792 Sentence denotes The diagnostic value of molecular testing of nonrespiratory specimens currently is unclear.
T179 23794-23843 Sentence denotes Diagnostics Pipeline in the Short and Medium Term
T180 23844-24180 Sentence denotes Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as for the accurate determination of live viral shedding among patients in the convalescence phase to inform de-isolation decisions (Figure 2).
T181 24181-24301 Sentence denotes Further, it is critical to advance solutions that require less well-equipped laboratories to curb the pandemic globally.
T182 24302-24535 Sentence denotes The Foundation for Innovative New Diagnostics (FIND) and others have created online resources to collate the rapidly evolving set of assays at various stages of development, from proof of concept to full regulatory approval (20, 53).
T183 24536-24745 Sentence denotes Simple antigen-based tests, if sensitive enough, might be useful in lower-resource and home settings to inform quarantine and spatial distancing measures for patients without severe illness and their contacts.
T184 24746-25075 Sentence denotes Novel technologies, such as Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)-based diagnostics are being used to develop rapid, simple, low-cost, portable, temperature-stable assays for deployment in the field in nontraditional and resource-limited settings, such as airports and border crossings (20, 51, 54).
T185 25076-25168 Sentence denotes Other technologies might be deployed to lower-resource settings if they can be standardized.
T186 25169-25368 Sentence denotes For example, it might be possible to leverage existing loop-mediated isothermal amplification testing networks established for other diseases, such as human African trypanosomiasis surveillance (66).
T187 25370-25390 Sentence denotes Other Considerations
T188 25391-25562 Sentence denotes Critical considerations for diagnostics used for epidemic diseases of public health importance include the quality assurance and regulatory frameworks surrounding testing.
T189 25563-25779 Sentence denotes Mature regulatory agencies have developed mechanisms to account for emergencies, such as the FDA's EUA stream, but pragmatic solutions must be found to facilitate wide-scale, independent evaluation of emerging tests.
T190 25780-25941 Sentence denotes Initially, the need for elaborate biosafety precautions and inconsistent recommendations for their application across regions severely hampered COVID-19 testing.
T191 25942-26370 Sentence denotes Although these continue to evolve, current recommendations in Canada and the United States acknowledge that nonpropagative work for molecular testing may be performed in containment level 2 conditions found in routine diagnostic laboratories and provide specific guidance on diagnostic testing of specimens conducted outside a biosafety level 2 laboratory, such as rapid respiratory testing performed at the point of care (67) .
T192 26372-26382 Sentence denotes Conclusion
T193 26383-26508 Sentence denotes The COVID-19 pandemic has dramatically highlighted the essential role of diagnostics in the control of communicable diseases.
T194 26509-26625 Sentence denotes Intensive diagnostics deployment probably contributed to the success of a few countries in controlling transmission.
T195 26626-26747 Sentence denotes Urgent clinical and public health needs now drive an unprecedented global effort to increase SARS–CoV-2 testing capacity.
T196 26748-26893 Sentence denotes Finally, the blinding speed with which COVID-19 has spread illustrates the need for preparedness and long-term investments in diagnostic testing.