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As the development of serological testing moves forward, lab to clearly state that the test has not been FDA cleared
it will be critical to use well-defined standard references as or approved, that it is authorized by FDA under an EUA,
part of diagnostic assay validation in order to standardize and that it is only authorized for use for the duration of the
assays developed by different labs to better understand declaration that circumstances exist justifying emergency
correlates of immune protection. In the interim, the choice use. Full FDA approval has not been granted to any lab,
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of the most appropriate test falls to the individual labs and test, or product for SARS-CoV-2. Labs claiming that they
clinicians using those labs to ensure validity. have “FDA approval” are doing so in contradiction of their
EUA status.
There are still a number of unknowns, such as: As per the FDA website on April 20, 2020, labs that
perform antibody testing are temporarily not required to
• Are individuals infected with SARS-CoV-2 who possess an FDA EUA. The FDA encourages, but does not
recover protected either fully or partially from require, labs that offer this testing to submit an EUA
future infection? 2 application. The FDA states that validation studies are
• Do all immunocompetent individuals mount an important in judging the quality of a test and will be
antibody response to all the viral proteins? required for an EUA. Therefore, we recommend that,
• How long do immunocompromised individuals ideally, clinicians use antibody tests that have an FDA
experience intact viral shedding? EUA but, in the absence of such, ensure that quality
• Will future viral mutations change the sensitivity validation studies were done.
and specificity of testing and the development of The astute clinician understands that while there is a
immunity? certain amount of regulatory oversight with EUA, it does
• Does having antibodies prevent community spread? not constitute formal federal review and approval of the
• Does having antibodies confer immunity and test or of the validation process. Manufacturers of tests
prevent recurrence? and the labs that utilize them are being given a level of
• How long might protective immunity last? trust that is needed and hopefully justified.
A study done in rhesus macaques sheds some light on Summary of Antibody Testing
the question of immunity. These animals show similar
patterns of infection and COVID symptoms from Samples • Whole blood, plasma, or serum.
SARS-CoV-2 as humans. Viral replication in the nose, Methods • Send to lab with EUA and validated ELISA
pharynx, lung, and gut, as well as interstitial pneumonia, or lateral flow membrane testing.
were seen after primary infection. Once symptoms • Point-of-care testing is not currently
resolved and they demonstrated a positive Ab test, the FDA-approved (as of April 20, 2020).
monkeys were re-challenged with the same dose of SARS- Timing • Higher sensitivity begins seven days after
CoV-2. No signs of infection, including viral replication in symptom onset.
any of the tissues, were seen in the re-exposed animals one Type • Testing for both IgM and IgG antibodies
month later. This gives some basis for the assumption measuring multiple viral proteins will
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that infection followed by positive antibody titers very increase both sensitivity and specificity.
likely confers some type of immunity, although this has yet
to be proven in humans. Some short term immunity is Interpretation
likely, but the length of that immunity is a very important If the clinician has a high index of suspicion that a
questions that remains unanswered. patient is likely to be or has been infected with
SARS-CoV-2, and testing returns a negative result, the
Regulations following questions may help to determine whether the
The current COVID-19 pandemic is a public health test should be repeated.
emergency and justifies the declaration of emergency use
authorization (EUA) of in vitro diagnostics for the If negative NAA:
detection and/or diagnosis of SARS-CoV-2. Labs seeking
EUA for their test must be CLIA certified in order to make • Was the swab collected correctly?
a submission to the FDA. After expedited review, the FDA • Was a sputum, saliva, or NP sample collected?
can grant EUA for a test when there is reasonable belief • Is the patient symptomatic?
that the test may be effective in diagnosing COVID-19, • Does the patient have a known exposure to a
that the known or potential benefits of using the test person with a positive test?
outweigh the potential risks, and that there are no • Where is the patient in the time course of the illness
adequate, approved, alternatives. (i.e., are they beyond the first week, when viral
BUYER BEWARE: The FDA outlines a number of RNA levels decline)?
conditions when it grants EUA, including requiring the

Messier—Primer on SARS-CoV-2 Testing Integrative Medicine • Vol. 19, No. S1 • Epub Ahead of Print 51