COVID-19 is revealing itself to be an unpredictable disease
as is the novel coronavirus that causes it.
Why do some people who get infected show no symptoms
but others become critically ill and die?
Why do some people who recover make antibodies
but others don’t?
Likewise, there are many questions about testing.
Who should be tested for the virus and when?
What’s the best sample type to use for testing?
And why, after more than half a year into this pandemic
are there still shortages of testing kits and supplies
that create bottlenecks for clinical laboratories
that perform these critical tests?
These and other questions
make the accuracy of testing all the more urgent.
By now the medical community is aware
that PCR tests performed in an accredited laboratory
are highly accurate,
but test results are influenced by many variables
that people may not realize.
Physicians and their patients likely do not fully appreciate
the impact of all the steps in the total testing process.
In the laboratory, we divide the testing process
into three phases:
pre-analytical (those are the things that happen
before the sample gets to the lab),
the analytical phase (which is the actual testing process),
and then the post-analytical phase
(which are the things that happen
after the test result is reported).
Today, I want to talk about the pre-analytical process
because it’s the source of most errors in patient testing.
Why is that the case?
Well, in short, it’s human error.
This is especially true with incredibly sensitive
and accurate tests like PCR tests
for the coronavirus where even small errors
can have profound effects on test results.
Let’s start at the sample collection step.
What type of sample is to be collected?
Nasopharyngeal, nasal, sputum, oral fluid?
Each of these has their pros and cons.
A nasopharyngeal sample requires a healthcare worker
with personal protective equipment
to obtain the sample
while nasal and oral fluid samples
can be self-collected.
But patients aren’t usually accustomed
to collecting their own samples
so that’s one possible source of error.
Another variable is the timing of collection
relative to infection.
Collect too early and the test result may be negative
because there’s just not enough virus to be detected.
Likewise, a nasopharyngeal sample
collected late after infection
may also produce a negative result
because the virus can no longer be isolated
from that source
and has migrated down into the lungs.
Serial testing from positive patients
has revealed prolonged viral shedding
that is intermittently detected:
results are positive, negative, and then positive again.
The bottom line is that testing
is just one piece of a bigger puzzle
and test results have to be interpreted
in light of other information.
Where is the sample being collected?
In a hospital or clinic
or at a high-throughput, drive-through location?
Healthcare workers are overwhelmed
and under pressure
and are often working in unusual
and uncomfortable circumstances.
And those conditions can certainly influence
the quality of sample and, therefore,
the actual test result.
Errors or lack of understanding
in the pre-analytical steps
can lead to false-positive or false-negative test results.
Don’t forget that PCR tests
can’t differentiate between organisms
that are infectious or not.
Unfortunately, errors in sample collection
are not always transparent to laboratorians.
While some preanalytical issues
can be detected by the laboratory, many cannot.
And we rely on our clinical colleagues
to provide us with quality samples
so we can provide them with quality results.
We know that sample collection errors
continue to need our attention
based upon studies of similar collection methods
for other viral diseases.
It’s also a reason that AACC
and other scientific organizations
have concerns about patient-collected samples
for in-home testing, particularly those collections
that are not observed by a healthcare worker.
Other types of pre-analytical errors that
can occur include misidentifying
the patient or the sample;
a poor-quality sample;
and the improper storage of samples before testing.
After samples are collected
they have to be transported to the lab.
And the time required for transport, the temperature,
and the transport media the sample is placed into
are among many factors
that can affect the test result.
Even as nurses, physicians,
and clinical laboratory professionals
continue their heroic efforts to the pandemic,
our teamwork must also include
the same passion for quality
that ensures reliable testing during normal times.
Proper specimen collection and transport,
training, and clear communication
among every professional on the healthcare team
are essential as our complex healthcare systems
rise to meet the challenge of this pandemic.