key: cord-350473-f47i7y5h
authors: Sen-Crowe, Brendon; McKenney, Mark; Elkbuli, Adel
title: COVID-19 laboratory testing issues and capacities as we transition to surveillance testing and contact tracing
date: 2020-05-27
journal: Am J Emerg Med
DOI: 10.1016/j.ajem.2020.05.071
sha: 
doc_id: 350473
cord_uid: f47i7y5h

nan

J o u r n a l P r e -p r o o f As of May 19 th , 2020, 11,834,508 COVID-19 tests have been performed in the US resulting in 1,523,534 (12.9%) confirmed cases 1 . The actual number of infected Americans is much larger. Antibody seroprevalence testing in Santa Clara County, California, estimates those infected between 2.49%-4.16% implying actual infections 50-85-fold larger than confirmed cases 2 . Another study concluded that undiagnosed COVID cases represent the infection source of 79% of documented cases 3 . Accurate testing will be crucial to controlling and understanding this pandemic. Estimation relies on testing kit accuracy (sensitivity/specificity). Low sensitivity will underestimate disease prevalence, while low specificity will overestimate. 2 Testing comes in two broad types, testing for nasopharyngeal viral RNA and serologic testing for antibodies, which occur in response to the disease. RNA testing is done with polymerase chain reaction (PCR) is cost-effective, easy to perform, and now available 4 . However, the PCR test has accuracy issues. Sensitivity of FDA-approved viral RNA tests range from 63%-95% (Table 1) [5] [6] [7] [8] . Sensitivity of RNA tests is dependent on the site of specimen collection. Sensitivity was highest in bronchioalveolar lavage (93%), then sputum (73%), nasal swab (63%), feces (29%) and blood (1%). 5 Another study found that patients with pneumonia often have negative nasopharyngeal samples, but positive lower airway samples 9 . The sensitivity of PCR tests have been estimated at 71%, resulting in ~30% of infected patients having a negative finding. Another drawback is the presence of viral RNA does not mean the virus is live, therefore, detection does not necessarily mean the virus can be transmitted 9 . RNA-based tests are limited to the setting of acute illness. Saliva-based tests offer promising results as a non-invasive and non-aerosol generating method of specimen collection 10 . Compared to nasopharyngeal tests, saliva specimens have high sensitivity (84.2% 10 ) and can be self-administered. 10 One study reported greater sensitivity in saliva samples as compared to nasopharyngeal swabs and less variability. 11 Reduced variability in samples taken from self-administered tests is helpful for mass testing because it preserves collection reliability and allows patients to send in their own samples from the comfort of their home.

The second type of test is serologic, which detects immunoglobulins (IgG and IgM) specific for SARS-CoV-2 and provides an estimation of population virus exposure 4 . One drawback of serologic testing is the lag period between symptoms and antibody formation-one analysis found patients do not begin to seroconvert until 11-12 days post-symptom onset 12 .The sensitivity and specificity of FDA-approved serologic tests ranges from 61.1%-98% and 90%-100% 13 . Many FDA-approved serologic tests have high sensitivity and specificity. For example, Cellex Inc. developed a rapid diagnostic test with 93.8% sensitivity and 95.6% specificity. Bio-Rad manufactured an ELISA test with sensitivity and specificity of 98% and 99%, respectively (Table 1) 13 .

There are also clinical associations with confirmed COVID-19 patients. An analysis of 119 patients with COVID-19 at from Wuhan University revealed an association with low urine specific gravity and increased pH 14 . In addition, the urine glucose and proteinuria correlated with severe/critical cases compared to mild/moderate 4 . The results imply that certain urinalysis profiles can be used to predict the severity of disease and possibly testing of asymptomatic patients that could be quarantined until a definitive test can be completed 14 .

To address the development of a reliable test, the Department of Health & Human Services (HHS) provided funding for the development of Simplexa COVID-19 Direct Assay and to QIAGEN to accelerate development of their RPS2 test 15 . Additionally, HHS is purchasing the ID NOW COVID-19 rapid point-of-care test (Abbott Diagnostics Scarborough Inc.) for public health labs (Table 1) 16 . The FDA is issuing Emergency Use Authorizations to expedite distribution 17 . States have differing amounts of laboratories authorized for testing ( Figure 1 ). The targeted distribution of tests to areas of high density (Figure 1-black diamonds) is paramount to ensure that resources are not undersupplied.

The road back to normalcy is contingent on accurate tests, allowing suppression of spread. When a localized outbreak occurs, it will be important to have reliable testing methods to promptly contain it. Random serologic testing can be used to surveil populations at high-risk for an outbreak. PCR tests can be used to assess those with active infection who may be asymptomatic.

Targeted distribution of tests needs to be to areas where COVID is more prevalent and where people are at higher risk. In addition to distribution, the quality of the tests require improvement. Many prospective tests in development report promising results in under 60 minutes, such as Mammoth Bioscience's CRISPR-based lateral flow assay (sensitivity:90%, specificity:100%) and United Biomedical's kit (sensitivity:100%, specificity:100%) (Table 1) . 13, 18 In the present era, technology allows diagnostics to be readily available. Understanding the current disease state in communities' plays a role in the acceptance of control measures that require individual actions. Now is the time to ensure systematic and coordinated efforts between the clinical, commercial and public sectors to leverage the power of testing to address the pandemic at our door.

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Diagnostic Testing for Severe Acute Respiratory Syndrome-Related Coronavirus-2: A Narrative Review

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2020;/j/cclm.ahead-of-print

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