COVID-19 Testing: Key Issues

COVID-19 Testing: Key Issues

April 23, 2020
COVID-19 Testing: Key Issues
The COVID-19 pandemic is affecting communities
carry out the large-scale clinical diagnostic testing needed
throughout the United States, with the country reporting the
during a pandemic response, and demand outstripped
highest number of cases and deaths from the disease
supply quickly as the country transitioned to community
globally. Containment and mitigation efforts by federal,
spread. The commercial sector—including commercial
state, and local governments have been undertaken to
laboratories and commercial test kit manufacturers—as well
“flatten the curve”—that is, to slow widespread
as clinical laboratories in hospitals and at universities are
transmission that could overwhelm the nation’s health care
seen as critical to achieving the scope of testing needed
system.
during the COVID-19 public health emergency. Despite
ramping up capacity across U.S. laboratories of all types,
Diagnostic testing is a critical part of the clinical
the country’s network of laboratories continues to face
management of COVID-19, caused by the SARS-CoV-2
challenges meeting the unprecedented demand for testing,
virus. In addition, both diagnostic and serology testing at
in terms of volume, speed, and accuracy. Currently the
scale may be a key component of efforts to ease mitigation
country performs approximately 150,000 tests per day, and
measures prior to the development, manufacture, and broad
a significant increase in capacity would likely require
distribution of a vaccine or effective therapeutic. Efforts in
additional infrastructure (more testing platforms, standing
the United States to rapidly develop, scale up, and
up additional laboratory facilities), in addition to
disseminate testing for COVID-19 have faced challenges,
maintaining testing at full current capacity.
including supply chain issues; a shifting regulatory
landscape; a lack of consensus around federal coordination
Types of COVID-19 Tests
of or strategy for testing; concerns with the accuracy of
Testing for COVID-19 currently involves both molecular
both molecular and serology tests; an early lack of data on
tests and immunoassays. Diagnostic testing for COVID-19
test results and capacity; and a delayed ramp-up by
generally relies on molecular tests that use nucleic acid
commercial laboratories and test manufacturers of both
amplification techniques such as polymerase chain reaction
centralized and point-of-care testing. In addition,
(PCR) to detect viral genetic material. These tests identify
manufacturing and quality issues with the nation’s initial
viral nucleic acid in samples taken from individuals’ noses
test—developed by the Centers for Disease Control and
or throats using swabs. This type of test is technically
Prevention (CDC)—resulted in significant delay in early
complex but well-characterized, generally requiring both
access to testing throughout the country. For more
specific instruments and highly trained laboratory
information, see CRS Report R46261, Development and
personnel. PCR tests may be high-throughput, so many
Regulation of Domestic Diagnostic Testing for Novel
samples may be run simultaneously, but the run time is
Coronavirus (COVID-19): Frequently Asked Questions.
generally several hours. PCR tests may be laboratory-
developed tests (LDTs), test kits, or point-of-care tests.
U.S. Laboratory Infrastructure
Point-of-care tests are usually faster and simpler to run, but
Public health testing may be used to help identify and
often only run a single or a few samples at one time.
contain the spread of a novel pathogen early in its
introduction into the country, as well as to detect and
COVID-19 testing may also be carried out using
monitor ongoing outbreaks. This testing relies on the CDC
immunoassays. This type of test detects immune system
and the U.S. network of state and local public health
proteins made by the host (antibodies) or viral components
laboratories, including some Department of Defense and
that stimulate the host’s immune response (antigens). Tests
international laboratories. In contrast, clinical diagnostic
that detect antibodies in the blood are called serology tests,
testing is carried out by a number of facilities, including
and they generally indicate either late active infection or
private commercial laboratories (e.g., LabCorp); hospital
exposure to and recovery from prior infection. Serology
and other clinical laboratories; and laboratories in academic
tests are not generally used alone for diagnosis of disease;
medical centers and universities. These two systems, while
rather, they may sometimes be used in combination with a
overlapping and connected, have distinct purposes. Clinical
molecular test for diagnosis. Serology testing also may be
testing may be centralized—a sample is collected and sent
used to identify individuals who can donate convalescent
to a central laboratory for testing—or decentralized, or
plasma as a possible therapeutic; to help guide development
occurring at or near the patient or point of care, commonly
of a vaccine; and to determine the extent and spread of
referred to as point-of-care testing.
COVID-19 in the general population, as well as the
infection fatality rate. Rapid antigen tests—which have not
Diagnostic testing for COVID-19, in part because it is
yet been authorized for use in the United States for COVID-
caused by a novel pathogen, was initially carried out by the
19—can detect viral antigens, generally in a throat or nose
country’s network of public health laboratories. However, it
swab. These tests are usually point-of-care, low-cost, easy
is generally not the role of the public health laboratories to
to use, and used for diagnostic purposes. However, these
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COVID-19 Testing: Key Issues
tests in particular tend to have lower accuracy than
(ability to detect a true negative); their accuracy may vary
molecular diagnostic tests.
based on the prevalence of the infection in the tested
population. In addition, technical issues such as cross-
FDA Emergency Use Authorization
reactivity with antibodies from commonly circulating
(EUA) Guidance for COVID-19 Testing
coronaviruses can return false positives. Serology tests are
Through guidance, the Food and Drug Administration
allowed to be marketed and used without an EUA, creating
(FDA) has allowed for modifications to the usual EUA
further unknowns about performance of these tests. The
process to facilitate a more rapid scale-up of testing. On
FDA is working with other federal agencies to provide
February 29, FDA announced a policy which allows
voluntary validation for these tests.
laboratories that have developed and validated their own
COVID-19 diagnostics to begin using the tests prior to
Supply Chain and COVID-19 Testing
receiving Emergency Use Authorization, as long as the
Supply chain issues related to COVID-19 diagnostic testing
laboratory notifies FDA and submits EUA materials within
have affected access to testing nationally. As the FDA has
15 days. This guidance was updated on March 16 to apply
granted EUAs for more LDTs and test kits—including
similarly to commercial test kit manufacturers, allowing
point-of-care tests—and testing volume has increased,
them to market test kits prior to receiving EUA. The agency
laboratories across the country have reported shortages in
also allowed tests to be used and marketed without EUA in
necessary supplies. PCR testing involves sample collection,
two cases: (1) where states have authorized laboratories to
nucleic acid extraction, and testing to identify presence of
carry out testing within the state and (2) for serology tests
the SARS-CoV-2 virus. Supplies needed for each of these
where the manufacturer notifies the agency and labels the
steps have been in shortage, including swabs needed for
test as required by the guidance. The agency reports that
sample collection; viral transport media needed to stabilize
more than 100 serology tests are currently being marketed
and store the sample after collection and during transport;
without EUA; serology tests may also be brought to market
RNA extraction kits and reagents needed to extract viral
under an EUA, and several have been. In addition, any at-
RNA from the sample prior to testing; and instruments, test
home test or self-collection of a specimen at home would
kits, and testing reagents needed to amplify and detect viral
need to have authorization prior to marketing. The agency
nucleic acid. Personal protective equipment (PPE) needed
has not yet authorized any at-home COVID-19 test. It did
during sample collection has similarly been in short supply.
grant authorization for the first at-home self-collection kit
for use with LabCorp’s PCR test.
These shortages have been anecdotally reported by
laboratories, and were documented in an April 3 report by
CLIA and the COVID-19 Pandemic
the Department of Health and Human Services Office of the
All clinical laboratories in the U.S. need to receive CLIA
Inspector General addressing hospitals’ experience
(Clinical Laboratory Improvement Amendments)
responding to COVID-19. The report notes that “severe
certification in order to test human samples for purposes of
shortages of testing supplies and extended waits for test
clinical diagnosis and treatment. Many questions have
results limited hospitals’ ability to monitor the health of
arisen during the COVID-19 public health emergency about
patients and staff.” FDA has worked with industry to try to
possible flexibilities in CLIA requirements, for example,
identify and mitigate shortages through modifications to
with respect to the certification process or personnel
test EUAs that allow for the use of alternate supplies when
qualifications, as well as the use of temporary testing sites.
carrying out a test and the establishment of an industry
The Centers for Medicare & Medicaid Services (CMS) has
hotline for device shortages. However, shortages reportedly
issued guidance to provide some flexibility with respect to
persist due to global demand and the unprecedented level of
CLIA requirements using its enforcement discretion. In
testing, as well as a lack of coordinated ascertainment,
particular, CMS clarifies that testing may be performed at
production, and allocation of supplies, and the FDA does
designated overflow sites and that laboratories may begin
not have the authority to allocate or distribute supplies.
testing upon receiving a CLIA number, but prior to
receiving a paper certificate.
Serology Testing to Determine COVID-
19 Spread in the United States
Accuracy Concerns with COVID-19
Many cases of COVID-19 are reportedly mild or
Testing
asymptomatic, and therefore go undetected. As such,
Accuracy concerns have arisen with respect to both
widespread serology testing would help to characterize the
molecular diagnostic and serological COVID-19 testing. It
scope and extent of the disease in the United States. CDC
has been reported that PCR tests for COVID-19 may return
reported in late March that the agency is in the early stages
as many as 30% false negatives (a negative result, where
of beginning serosurveys—surveys that measure the
the individual is a true positive). While no diagnostic test
proportion of a population that has antibodies to an
performs with perfect accuracy, certain issues may result in
infection—to gauge the spread of COVID-19. The first of
lower accuracy. PCR-based tests are generally very
these studies is already underway in six major metropolitan
accurate, but problems can occur with sampling technique,
areas, including New York City and Seattle, and it aims to
storage and transport, and the extraction step. In addition,
“monitor how many people develop SARS-CoV-2
viral load varies during the course of an infection and can
antibodies over time.” NIH also recently reported it has
affect the amount of virus in a collected sample.
undertaken a large serosurvey to determine how many
healthy adults have been exposed to COVID-19.
Serology tests authorized by FDA generally have high
sensitivity (ability to detect a true positive) and specificity
Amanda K. Sarata, Specialist in Health Policy
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COVID-19 Testing: Key Issues

IF11516

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