Review: COVID-19 Diagnostics

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Among other measures, large-scale diagnostic testing for COVID-19 might have helped contain the disease in the U.S., as it did in Hong Kong, Singapore and Taiwan. In Science Translational Medicine, Ralph Weissleder, MD, PhD, director of the Center for Systems Biology, attending clinician in Interventional Radiology at Massachusetts General Hospital and radiologist at Mass General Cancer Center, Hakho Lee, PhD, director of the Biomedical Engineering Program at the Center for Systems Biology and Hostetter MGH Research Scholar, and Mikael J. Pittet, PhD, director of the Cancer Immunology Program at the Center for Systems Biology at the Massachusetts General Hospital Research Institute and Samana Cay MGH Research Scholar 2015-2020, and colleagues review the utility and challenges of current diagnostics for COVID-19.

Nucleic Acid Tests

In nucleic acid tests, a sample of viral RNA is reverse transcribed into DNA, which is then amplified through polymerase chain reaction (PCR). Nucleic acid tests are the most widely used tests for detecting SARS-CoV-2 and are increasingly run on automated platforms that can be completed in several hours.

The sensitivity of nucleic acid tests varies according to the duration of illness, the specific clinical COVID-19 syndrome, the site of specimen collection, the quality of specimen collection and the viral load. False-negative SARS-CoV-2 tests have been reported to occur in ~30% of patients with COVID-19 (range, 10%–40%). If a patient's symptoms or imaging results suggest a high probability of COVID-19, testing should be repeated after a single negative result.

With point-of-care PCR kits, test results are known within about 30 minutes or, in the case of one commercial test, about 15 minutes. The rapid tests typically are not yet automated and are more expensive.

Serologic Tests

Serologic tests assess one or more antibodies (IgG/IgM) and, for some tests, other proteins that indicate a host response to SARS-CoV-2. The uses of serologic tests include:

• Assessing an individual's immune status
• Researching the duration of immunity
• Determining previous viral exposure in a population for retrospective assessment of the efficacy of control measures
• Evaluating surrogates of immunity for vaccine development

The accuracy of serologic tests can be near 100% when samples are acquired 20 days after SARS-CoV-2 infection or first symptoms of COVID-19. At earlier times, the sensitivity and specificity are lower because the immune response is evolving.

Between mid-March and mid-April, 2020, the FDA allowed companies to sell antibody tests without submitting proof that they work. Now the companies must submit evidence of efficacy, but there is still a need to verify the accuracy of serologic tests in the field. The Infectious Disease Society of America recently released guidelines for verification, and two global efforts are underway to evaluate SARS-CoV-2 antibody tests.

Managing COVID-19 Within Populations

When carried out broadly and repeatedly, the results of nucleic acid tests diagnose pre-symptomatic and asymptomatic carriers of SARS-CoV-2 and thus help define infection rates across populations. Similarly, frequent and widespread serologic testing could help determine what fraction of the population may be immune to SARS-CoV-2 and which individuals may safely rejoin the workforce.

The lack of longitudinal testing in the U.S. is problematic because it is inhibiting the ability to understand the evolution of COVID-19.

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