[Download PDF (Español)]
There is broad recognition that the unprecedented COVID-19 pandemic requires clinical laboratory
testing as part of the worldwide response to this health crisis. To detect SARS-CoV-2—the virus that causes
COVID-19—in infected individuals, the primary laboratory tool has been molecular diagnostic tests. While
these tests inform clinicians of individuals who are currently infected by identifying the presence of SARS-CoV-
2 genetic material, there is a need to gain insight into the prevalence of SARS-CoV-2 in the general
public. Serologic testing, which looks for antibodies specific to SARS-CoV-2, can identify individuals who
have been infected and may assist in epidemiologic initiatives and contact tracing. Clinical laboratory
professionals are invaluable for the evaluation, use, and interpretation of these clinical tests and can help
policy makers and public health officials develop strategies to constrain the pandemic.
Utility of Serology Testing in COVID-19
Serology tests are blood-based tests that can be used to determine whether people have been
infected by particular pathogens. The immune system recognizes pathogens as foreign and mounts a
protective response involving the development of antibodies. The presence or absence of SARS-CoV-2
specific antibodies can determine whether a person has been infected by the virus.
Diagnosis and management
Serologic testing may play a role in vaccine development and identification of recovered patients who
can donate blood to help others fight the infection. Serologic testing may also be a useful diagnostic
tool in patients who have a longer (i.e. greater than 1-2 week) history of COVID-19 symptoms but have a
negative molecular test. In such cases, the patient may have stopped producing virus and therefore may
no longer be infectious. Serologic testing may be complementary to PCR-based diagnostic testing for
management of SARS-CoV-2 infection.
Surveillance and prevalence
Serologic testing has limited utility for surveillance and identification of the prevalence (i.e. the percent of
people infected within a population) of disease. The time required for antibody production after infection
by SARS-CoV-2 must be considered when surveillance testing is utilized. While serologic testing can
provide insight into the level of SARS-CoV-2 exposure within our communities, there are limitations for its
use, and test results must be interpreted judiciously.
Limitations of Serology Testing
Serologic testing should not be used as a primary method of diagnosing an acute infection or
exclusion of SARS-CoV-2 infection when a patient is experiencing symptoms. SARS-CoV-2 can be
detected in infected individuals before antibodies are detected. While research into the course of SARS-CoV-
2 infection is ongoing, it is known that antibodies take time to be produced by the immune system.
Serology tests that are performed too early during infection will likely be negative, despite the presence of
Most importantly, it is unclear whether the antibodies produced after infection by SARS-CoV-2 result
in lasting protective immunity. Research is underway to elucidate the protective effects of SARS-CoV-2
antibodies and duration of immunity.
SARS-CoV-2 Testing Performance
Serologic test performance, like all laboratory tests, can be evaluated using the following metrics:
Ideally, serological tests detect only the antibodies for the particular virus being tested, in this case SARS-CoV-
2. However, there are many viruses, including other coronaviruses, that people may have been
infected with in the past. Some serological tests may not be able to distinguish between antibodies
produced against these viruses versus the antibodies specific to SARS-CoV-2. This phenomenon is
called cross-reactivity and can cause false positive results. Clinical laboratories play a critical role in the
evaluation of serological tests to safeguard against these limitations and minimize false positive results that
may undermine disease prevention strategies.
Sensitivity and Specificity
The sensitivity of a test refers to how frequently a test correctly identifies the presence of antibodies
following infection (i.e. does detect the antibodies when they are there). Specificity indicates the frequency
with which a test correctly identifies the absence of antibodies in a person who has not been infected (i.e.
does not mistakenly detect antibodies that are not there). A test that has high sensitivity may have reduced
specificity, resulting in some degree of false positive results.
Positive and negative predictive values are two essential calculations that provide insight into the
accuracy of positive or negative test results within the population tested. These values are based on the
test sensitivity and specificity, but also incorporate and are dependent on the prevalence of SARS-CoV-2 in
Positive predictive value (PPV) indicates the number of positive cases that a test accurately identifies out
of the total number of positive cases within a given population. Negative predictive value (NPV) defines
the accurate detection of negative cases. PPV increases with increased disease prevalence, whereas NPV
decreases with increased disease prevalence.
Serology tests are manufactured by many companies that report a wide range of sensitivity and specificity
values. If a serologic test that is 95% sensitive and 95% specific is used to test a population of 10,000 people
in which 20% (2000) of individuals have antibodies, the test would correctly identify antibodies in 1,900 of
those 2000. However, it would incorrectly identify antibodies in 400 people of the remaining 8000 who do
not have antibodies. If that same test is used to test a population of 10,000 people in which only 5% (500)
have antibodies, the test would correctly identify antibodies in 475 of those 500. However, it would also
incorrectly identify the presence of antibodies in 475 people among the 9,500 individuals who do not have them. In the first situation out of the 2300 people who tested positive, 82% would actually have antibodies,
whereas in the second situation, out of the 950 who tested positive, only half would have antibodies.
Until a clear picture emerges regarding prevalence, serologic test results should not be used as the sole
basis for clinical or public health policy decisions.
Clinical laboratory tests are regulated to ensure that they provide accurate results. A number of
commercially produced serological tests for SARS-CoV-2 antibodies have received FDA Emergency Use
Authorization (EUA) for clinical use and some laboratories are now beginning to use these tests. Other
laboratories are choosing to develop their own serologic assays as laboratory developed tests (LDTs). It
is the Association for Diagnostics & Laboratory Medicine’s (ADLM) position that clinical laboratories should only use assays that have received an EUA by the
FDA, or LDTs that have been developed and clinically validated by a laboratory certified to perform
high complexity testing. Clinical laboratories are responsible for validating and implementing all tests,
regardless of FDA EUA status or LDT and ADLM does not support at-home serology testing at this time.
There is significant interest in using rapid response tests broadly in hospitals, clinics, and physicians’ offices,
particularly in medically underserved areas. In these settings, a test performed at the point of care (near
patient) by non-laboratory personnel requires designation as a waived test. As of May 5, 2020, there are no
FDA EUA serologic tests for SARS-CoV-2 that may be used in a waived setting. At this time, all rapid response
tests must be performed within a moderate or high complexity setting of a certified clinical laboratory.
In summary, serology testing is complementary to molecular diagnostic testing in managing the COVID-19
pandemic. It may play an important role in assessing the prevalence of the disease and may support
epidemiological efforts such as contact tracing while research into anti-viral therapies and vaccines
continues. Although there are many various serologic tests coming to market, their accuracy, reliability,
and interpretation must be evaluated by laboratory medicine professionals before these tests can be
used effectively. The FDA continues to adapt its guidelines based on real-world experience and new data
to balance the risks and benefits of granting test authorization. ADLM commends the FDA for its continued
diligence in holding manufacturers accountable for their tests and marketing practices.
Our understanding of COVID-19 and the tests used to detect and manage infection will increase as
our global scientific and clinical communities work together to understand this novel virus. Laboratory
professionals play an indispensable role in developing and performing diagnostic and serologic tests and
providing guidance in their proper use and interpretation.
ADLM supports the efforts to expand testing in an evidence-based manner as this pandemic continues to
unfold. The association advocates for vigilance in implementing serologic testing to provide better patient
care through laboratory medicine.