By Joseph Constance
As the nation reopens businesses and moves toward a version of “normalcy,” there continue to be concerns over COVID-19 testing, and how testing will impact reopening.
Molecular (PCR) tests, antigen tests, and serology tests all play significant roles in determining who has been infected with the coronavirus, and who has antibodies and immunity. PCR assays detect viral RNA, and diagnose active infection with SARS-CoV-2.
An alternative to PCR tests are antigen tests that detect the presence of viral proteins in saliva or tissue swabbed from the nasal cavity. Antigen tests are less expensive, and yield results in minutes, indicating if there is an active infection. Serologic, or antibody, tests look for the presence of antibodies in blood, which indicate a previous infection with SARS-CoV-2.
But much testing has been beset with credibility issues. For example, several rapid antibody test kits approved by the FDA do not have the required regulatory approval from China and the US.
As of June 15, the U.S. Food and Drug Administration (FDA) has removed more than 40 coronavirus antibody tests from the market, which the agency deemed not trustworthy.
And we still don’t know how long a person’s immunity will last. There also are concerns about how to combat false-positive and false-negative test results, as they can mislead on the road to recovery.
Meanwhile, clinical laboratories generally have struggled to meet the demand for testing, according to survey results from the College of American Pathologists (CAP). Among the labs’ challenges is their ability to obtain supplies necessary for COVID-19 testing.
Of those laboratory directors responding to the survey:
- 69% had difficulty in acquiring test kits to conduct COVID-19 testing;
- 66% reported difficulty in acquiring nasopharyngeal swabs;
- 62% found difficulty in acquiring viral transport media-universal transport media to conduct the tests.
A New Normal
What will be the new normal for the labs? They face uncertain times: loss of revenue, emergency loans, and dealing with remote working to keep lab employees safe from exposure to the coronavirus.
“The new normal is going to involve making do with less revenue,” said Dr. Carmen Wiley, president of the American Association of Clinical Chemistry (AACC). In an interview, she explained this will be a major challenge faced by clinical labs. “Both hospital and commercial laboratories have suffered significant losses in revenue due to the pandemic because of a lower demand for non-COVID-19 services. Some labs reduced employee hours or furloughed employees who were not needed,” she explained.
The AACC has identified certain challenges that it believes must be addressed, notably by the federal government, to fully and safely reopen the country:
- The federal government should develop a testing strategy that establishes a common terminology, identifies challenges, specifies necessary resources, sets forth a plan for acquiring and distributing needed materials, and creates benchmarks and timelines for measuring progress;
- The federal government should ensure that supplies are manufactured and distributed to labs in a timely manner;
- Congress should continue to provide funding to CDC so that it can build the public health infrastructure to address the pandemic crisis;
- The federal government should reimburse laboratories sufficiently for accurate antibody tests to facilitate access to them;
- The government should continue to grant financial aid to all healthcare facilities to offset financial losses from the pandemic.
Wiley said that current distribution pathways are not effectively distributing supplies where needed. “So in addition to laboratories using (supplies) being supplied to their states, they also are working through their regular distributors to get the supplies they need, including reagents, collection supplies, and the like.”
As a backup plan, some AACC member laboratories are establishing relationships simultaneously with different test manufacturers so the labs can be assured of having a reliable inventory. If one manufacturer cannot supply its test, a lab could shift to the other supplier and continue to offer testing in their community, according to Wiley.
Another important issue: Labs should have a plan in place to address false-positive test results. False results usually occur when a sample is collected incorrectly. “But it’s very hard for a lab to know if a sample was collected improperly,” explained Wiley.
A lab can minimize the number of false-positive results by confirming initial positive results by testing the sample using a different method, often another supplier’s test, to see if that test also returns positive. That would enable the lab to determine if the initial results were a true-positive or a false-positive, according to Wiley.
In May, the U.S. Centers for Medicare and Medicaid Services (CMS) announced new Healthcare Common Procedure Coding System (HCPCS) codes for testing patients for SARS-CoV2. Reimbursement for various tests ranges from $35.91 to $45.23.
But Wiley is concerned that that the COVID-19 reimbursement structure be appropriate for labs. “We need to make sure that reimbursement takes into account the true cost of testing,” she explained. For example, regarding false-positive test results, “If a lab has to do a new additional test, let’s make sure that the additional test is covered in the reimbursement,” she added.
Antibody Testing Challenges
Wiley raised concerns about using the results of antibody testing to determine the level of COVID-19 exposure in the community. “Until we know more about the prevalence of COVID-19, the results of surveillance studies that use antibody tests alone shouldn’t be used to make public health policy decisions,” she said.
“Antibody tests cannot determine precise immunity to COVID-19. We don’t know how many antibodies are required for a person to be immune, and for how long that immunity lasts, and there are problems with false-positive test results. The coronavirus is still so new that we don’t know everything about it. We don’t want to make broad, sweeping public health decisions until we’re able to truly understand the benefits and limitations of doing this testing specifically for COVID-19,” she explained.
In addition, the U.S. Centers for Disease Control and Prevention (CDC) has reminded us about the limitations and unknowns concerning serologic antibody testing. As the CDC states, “Serologic testing may play a role in a back-to-work strategy provided it can be shown that serologic testing can reliably infer immunity.”
Investigators at Imperial College London concur that little is known about coronavirus and how long immunity may last. In research published in the Journal of General Virology on May 20, they wrote that most people infected with SARS-CoV-2 display an antibody response between 10 and 14 days after infection. In some mild cases, detecting antibodies requires a long time after symptoms, and in a small number of cases, antibodies are not detected.
They add that there is little data regarding the longevity of the antibody response to SARS-CoV-2. Antibodies may disappear over time, so reinfection of previously mild SARS-CoV-2 cases is a realistic possibility that should be considered in models of a second wave and the post-pandemic era.
With the number of confirmed cases of the coronavirus passing 8 million worldwide and 2 million in the US, the key to reopening safely appears to lie in the successful development of a COVID-19 vaccine. Such a vaccine might not be ready for clinical use before this pandemic has ended. However, it will be vital if there is a second wave. And just as importantly, it should be equitably available worldwide.