COVID-19 Testing

CLICK TO EXPAND // Updates as of May 19, 2020

Since the publishing of this article, there have been some key updates to lab testing.

First, Quest Diagnostics has now begun offering patients the ability to order antibody testing themselves without the need for a doctor’s order (1). The test appears to be $119.00 to order, which is significantly more expensive than the price for doctors and with insurance coverage, but it is an option for individuals for want to get testing very quickly. Those ordering this type of test arrange a time to go to Quest draw site to have their blood drawn.

In reviewing the specific antibody tests used by Quest, it appears that they are primarily using a test from Abbott and one from Euroimmune, which have both received FDA Emergency Use Authorizations (EUAs). Overall it appears that they are using Abbott’s test primarily, which has the most impressive accuracy with regards to sensitivity and specificity of nearly any test I have seen (3). Tests like Abbott’s that are nearly 100% specific have a nearly 0% false positive rate, meaning that if you test positive with the antibody test, it is almost assuredly COVID-19 and not another coronavirus or virus altogether. While there have been some recent concerns regarding the rapid PCR test from Abbott, the antibody test appears to be a very reliable test with high specificity and sensitivity.

Second, Labcorp has started to offer an antibody test as well (4). In reviewing data presented from Labcorp, it appears that they are also utilizing the antibody tests from Euroimmune and Abbott, just like Quest. From what I can gather, for individuals receiving doctor’s order, but going through cash pay means, Labcorp’s test appears to be a little cheaper than Quest’s, in the neighborhood of $50-60 as compared to $65-75 with Quest. At this stage, with still much uncertainty regarding the numbers of individuals with COVID-19 antibodies, I believe is it prudent to utilize the most specific antibody tests available to prevent false positives. At this juncture, both Quest and Labcorp are utilizing the same highly specific antibody tests, and I would encourage anyone who wants an antibody test at this time to seek out these means if it is safe to travel to a blood draw location.

References and Links

  1. https://questdirect.questdiagnostics.com/products/covid-19-immune-response/b580e541-78a5-48a6-b17b-7bad949dcb57
  2. https://ir.questdiagnostics.com/press-releases/press-release-details/2020/Quest-Diagnostics-Begins-to-Perform-COVID-19-Antibody-Testing/default.aspx
  3. https://www.fda.gov/media/137383/download
  4. https://www.pixel.labcorp.com/blog/difference-between-covid-pcr-test-vs-serology-test
  5. SARS-CoV-2 Antibody IgG (Test # 164055) Assay Summary

Now weeks into a national lockdown, we have all likely seen reports regarding the challenges in obtaining and performing testing for patients with a suspected COVID-19 infection. Given the inadequate number of testing kits that were available as the number of known cases was increasing, many individuals who were experiencing mild to moderate symptoms that could have been related to COVID-19 were unable to obtain appropriate testing or testing on an appropriate timeline. With the wealth of information (often conflicting) that exists about testing and the number of changes that have taken place in the past few weeks, I wanted to provide you all with a brief summary about my current understanding of testing and how things will continue to evolve over the coming weeks.

Note: The topics explored in this blog are incredibly fluid with updates and changes happening daily. The material as originally presented is up to date as of Tuesday April, 21st, 2020. We will seek to provide updates to this blog after the date of publication as important information or changes arise.

Test History: Polymerase Chain Reaction (PCR) Testing

Initial testing policies and continued testing efforts for those with moderate to severe symptoms has involved the collection of human cells using a naso-pharyngeal swab (swab up the nose) or occasionally an oro-pharyngeal swab (swab in the throat). After the collection of these cells and their mixture into the testing medium, the lab would then perform a test known as a PCR (Polymerase Chain Reaction) to essentially look for evidence of the virus’ genetic material (it has RNA instead of our DNA) in the collected set of cells. As the virus replicates predominantly in tissues of the respiratory tract, finding evidence of its genetic material from cells in the respiratory tract in someone with symptoms most consistent with the best known symptom pattern of COVID-19 is arguably the best method of identifying someone who is sick with an active infection of COVID-19. While this type of testing has been and will remain critical for identifying those with active infections as well as those with more severe infections in hospital settings, for those who have had mild symptoms and have now recovered or who continue to have major challenges in accessing PCR testing, we must look to newer alternatives.

Overview of Antibody Testing

Another type of emerging test outside of the PCR (genetic) test is known as an antibody test. As part of our own immune response to external pathogens including intracellular pathogens such as a virus, we may develop antibodies to various aspects of the pathogen. Antibodies are essentially specialized proteins with two functional components. One portion of the antibody is tasked with recognizing and binding to various protein patterns such as those of a virus while the second portion is tasked with binding to our own immune cells in order to further communicate what it has recognized on the pathogen portion. Over the course of an infection, we will utilize different types of antibodies that have specialized structures and thus specialized functions, with some antibodies being more helpful and critical for the earlier stages of an infection and others being more helpful in later stages and after the infection has resolved.

Role of COVID-19 Antibody Testing

As you can likely start to see, testing individuals for antibodies to COVID-19 would be a great way to determine who is having or has had an immune response to the virus. While there is still much that we do not know about individuals who test positive on such antibody tests (for example, a) Do they have lifelong immunity? b) Are they still actively shedding the virus in a way that makes them contagious? c) Is the antibody test actually showing evidence of an immune response to COVID-19 and not just another type of more benign coronavirus?) the information antibody testing can provide will help us more quickly return to a degree of normalcy and better understand the extent of the virus’ spread. While it may feel like we should immediately begin testing everyone with antibody tests, we need to make sure we understand the information the test is actually telling us, the reliability of the information it is providing, and the clinical picture of the person we are testing in the first place.

Below I have outlined the primary scenarios where antibody testing would be the most helpful starting with the best candidates and ending with the less optimal scenarios.

1. Previously symptomatic individuals with symptoms that could have been attributed to COVID-19 with no previous PCR testing who have now recovered.

Individuals who are no longer symptomatic but previously showed symptoms such as fever, shortness of breath, chest tightness and loss of sense of smell at least 5-7 days prior to considering antibody testing are ideal candidates for antibody testing. Depending on the timeline from the first onset of potential COVID-19 symptoms, PCR testing in a “recovered” and asymptomatic individual could result in a negative test and the perception that one never had the virus. Testing for antibodies at least 5 days after the first onset of symptoms, however, can potentially identify the nature of any immune response to the virus and thus help us to discern whether one’s previous symptoms were actually related to COVID-19 or to some other cause.

2. Mildly symptomatic individuals who are unable to obtain PCR testing and have had symptoms for at least 5 days.

These individuals have been the most under-represented with most current PCR testing policies. Getting them access to a test that can be performed and resulted in a 48 hour period would be greatly helpful for determining one’s individual course of treatment and for our greater efforts at understanding infection rates.

3. Asymptomatic individuals with known (positive PCR test) close contacts who exhibited symptoms at least 2 weeks prior.

There are hundreds of thousands of individuals who are currently asymptomatic in various versions of quarantine given a known and not just theoretical exposure to someone with COVID-19. It would be helpful to understand which of these individuals indeed actually contracted the virus and have developed an immune response- antibodies to the virus. Interpreting testing results in this group does become a little more challenging, however, when one lacks symptoms, and therefore lacks a theoretical timeline for when we would normally expect to see antibodies. For asymptomatic individuals with known COVID-19 exposures, I would suggest waiting at least 10 days to 2 weeks after the date of known exposure to the positive close contact before pursuing the antibody testing. Even with this timeline, however, one could still test negative for antibodies even though one is currently in an evolving state of infection, but in a state that is too early for detecting antibodies.

4. Asymptomatic individuals with theoretical exposure to the virus.

As you likely realize, this group of individuals is both the largest, most variable and thus the most challenging to accurately assess with an antibody test. Many can make arguments for expanding and offering testing to these groups, which we will likely be doing in the coming weeks and months, but I list this group and the testing scenario at the bottom as there are just so many variables for individuals in this bucket that could alter the timing and interpretation of antibody testing. In my opinion, testing such a population should start with the most ubiquitously exposed groups- our essential workers. While many of the essential workers fall into one of the other scenarios described previously, many more are still living in a world wondering have I been directly exposed to an actively infected individual in a state of susceptibility? It makes sense to me then, for certain corporations and large companies employing individuals in areas of essential need to strongly explore these tests for their employees in order to better understand their current level of exposure and identify who may be better candidates for continuing to work in these exposed roles.

How Reliable is COVID-19 Antibody Testing?

In the last week alone there has been a huge surge of companies offering various versions of COVID-19 antibody testing kits. As you can likely imagine, there is some money to be made by companies- while not entirely unjustly, and the current FDA approval process for such tests is essentially non-existent at least in how it was formally designed outside of emergency proceedings, leading many like myself to be quite cautious in assessing the available testing landscape. At the time of writing (April 21st), there have only been 4 antibody tests that have received an officially emergency use authorization – not the same thing as a full approval, so that it can be offered in various clinical laboratories. Of the 100 or so other lab companies that have submitted testing registration information to the FDA and/or are currently marketing their antibody tests, the only requirements set down by the FDA are essentially that the test must be reliable and accurate and that the lab company cannot advertise that its test is actually diagnosing a COVID-19 infection (1).

Excerpt from an FDA Statement on April 7th

“In March, the FDA issued a policy to allow developers of certain serological tests to begin to market or use their tests once they have performed the appropriate evaluation to determine that their tests are accurate and reliable. This includes allowing developers to market their tests without prior FDA review if certain conditions outlined in the guidance document are met. The FDA issued this policy to allow early patient access to certain serological tests with the understanding that the FDA has not reviewed and authorized them.”

With all of this in mind, we must be open, but careful in the next phase of testing implementation with the various types of antibody tests that will be administered. While the antibody tests themselves are all similar in nature, the specific viral proteins to which the antibodies are developed (amidst many other testing characteristics) are quite different and their individual ability to detect the presence of COVID-19 antibodies and ability to correctly indicate when they are not present is going to be quite variable.

Given that we will not have any formally approved FDA tests during this emergency period, we will primarily have to rely on data presented by the lab technology companies and the testing labs themselves about the usefulness of specific antibody tests. While it would be easy to think that the first test that received an FDA emergency use authorization — an antibody test from the lab Cellex — is the best antibody test for patients, this would be making a logical fallacy as the Cellex test is simply the first of what will be many more tests getting the emergency use authorization moniker.

From what is published from the FDA regarding the Cellex test, it appears to have around a 93% sensitivity (ability to detect the antibodies in a sick individual) and around 96% specificity (ability to correctly determine who is not sick) [2]. As you can see, the test is still not perfect, and will occasionally not detect antibodies when someone actually has them and can even indicate that someone has the antibodies when in fact they actually do not, arguably the more problematic issue. After looking at some of the other published data from other antibody tests, most tests appear to have sensitivities around 85-95% and specificities around 93-100%

While it is impossible to get fully comprehensive data regarding all the newly marketed antibody tests, Johns Hopkins has provided a nice centralization of tests that have received FDA emergency use authorizations or tests that have been approved by similar FDA organizations in other countries (3). It should be noted that many of the tests that have been used in other countries such as China and that are listed on the Johns Hopkins site are the tests themselves than many of the lab testing companies seeking emergency use authorizations are using through specified partnerships. In addition, the FDA continues to regularly post updates about new tests, both PCR and antibody tests that are receiving emergency use authorizations that you can find from the cited reference (4).

Obtaining COVID-19 Antibody Testing

Now you may be asking: How do I get an antibody test and what will it cost? The answers to these questions will indeed be incredibly variable, but the first place to start is to contact your primary care provider or primary physician providing services for you. At this juncture with the antibody tests being so new, many practices may or may not have access to the tests themselves and/or the ability to draw your blood to perform the tests. As of the writing of this article, only one of the major clinical laboratories, Quest Diagnostics, has started to offer an IgG antibody test, however, I have not been able to see any of the test’s methodology or statistics including its sensitivity or specificity, making it very challenging to recommend as of yet. Another large clinical Labcorp does not appear to be currently performing any antibody testing, however they have just received an emergency use authorization for one of its PCR tests to be performed at home instead of at a health care provider’s office. While the testing landscape will invariably change over the coming weeks, there appears to be some initial challenges for patients and physicians to obtain reliable and authorized antibody tests.

While the testing options at this point may be limited, I am aware of a CLIA certified laboratory known as KBMO Diagnostics that has a FDA registered antibody test with adequate sensitivity and specificity that is currently available for physicians to order and for patients to have performed and resulted in around 48 hours. KBMO’s specific antibody test has been utilized in China in approximately 2 million individuals and has a sensitivity of around 87% and a specificity near 100%. The KBMO Diagnostics team has also arranged for a network of mobile phlebotomists who are able to draw the blood necessary for the test without individuals leaving their homes. The test collection kit can be ordered and drop shipped to the patient or wherever the testing is to be performed. The test itself including the rapid shipping to and from the patient is $150. The mobile phlebotomy services start at $100 per draw, but cost only $50 for subsequent draws at the same location. At the current time, payment for the testing kits must be provided at the time of ordering. While the cost of the test is not inconsequential, there is language in the previously passed CARES Act that indicates that health insurance companies (commercial) will be required to cover COVID-19 testing services including services provided from clinical labs or providers that are out of network. While there are many potential issues that could arise from this seemingly good element of the CARES Act, in the case of the KBMO antibody test, one should theoretically be able to submit paperwork (like a superbill) including testing and diagnostic codes to one’s insurance carrier after paying for and performing the KBMO antibody test even through the KBMO lab is an out of network lab facility.

When it comes to point of care or in-home antibody tests that can be performed using a finger prick to obtain capillary blood, 1 of the 4 antibody tests that have received emergency use authorizations is for an in-home testing kit (5). After reviewing the lab company and affiliates websites as well as the scientific media pieces describing the test kits approval, however, it is still unclear to me how as a provider I can actually get one of these tests ordered for my patients and at what scale these tests are being produced. As you can imagine, this process is both frustrating and evolving and I am confident over the coming days and weeks there will be greater access to authorized tests for both providers and patients.

What Does All of This Mean?

As you can imagine, everyone would love to know exactly how far the virus has spread, who precisely has been affected and do those affected with positive antibody tests now have immunity? We simply do not have answers to these questions, and while we must be tempered in our conclusions, we must be willing to strategically deploy testing to better understand the nature of this pandemic and start to more comprehensively answer these questions. A preliminary study (yet to be formally peer-reviewed) coming out of Stanford appeared to indicate, after utilizing antibody testing for a larger population of individuals within a defined geographic region, that there was evidence of positive antibodies and suspected viral exposure in 2-4% of the population tested, a 50-85 times greater number than current case estimates derived almost exclusively from PCR testing appear to indicate (6). While the hypothesis that a larger percentage of individuals (mainly asymptomatic) have been exposed and developed antibodies to the virus is strongly supported, the statistical calculations and models used in this previously mentioned study and in other similar reports are flawed in a number of ways, mainly do to the limitations in the sensitivity of the antibody tests used, the still relatively low number of cases or prevalence of antibodies and sampling bias related to the selection of participants. It is likely safe to say more people have been infected than current case data shows, with most of these unreported cases coming from asymptomatic individuals, but the exact percentages of cases within certain geography regions remains a mystery.

Conclusions

Testing for COVID-19 is an evolving process with the latest evolutions involving the new access to antibody tests looking for signs of an immune response. Despite the inclination to immediately deploy these types of tests for all Americans, the FDA has currently allowed large scale marketing of unproven antibody tests. It will be critical over the coming weeks, to balance the risks and benefits of utilizing unproven testing with the need to have some form of testing performed across large populations. While I suspect there to be improved oversight by the FDA over the coming weeks, there is currently too much uncertainty about which antibody tests are the most accurate, reliable and readily accessible. For those interested in receiving antibody testing, you should contact your local medical professional and can consider exploring the resources provided below about one of the antibody tests provided by KBMO Diagnostics.

KBMO Diagnostics Testing Information

Test Details: https://kbmodiagnostics.com/

Physician Ordering Form: https://kbmodiagnostics.com/physician-order-form-covid-19-kits/

Detailed Test Description Slides: https://kbmodiagnostics.com/wp-content/uploads/KBMO-Diagnostics-COVID-19-Rapid-Test.pdf

COVID-19 Diagnostic and Procedure Codes

Test Diagnostic Codes (7)

One Step Antibody Tests: 86328 (Ex. KBMO Antibody Test)
Two Step Antibody Tests: 86769

Potential Diagnosis Codes

R05: Cough
R06.02: Shortness of breath
R50.9 Fever unspecified
(These codes would be reasonable for people in Scenarios 1/ 2 depending on one’s symptoms)

Z03.818: Encounter for observation for suspected exposure to other biological agents ruled out.
(This code is for those with a THEORETICAL exposure -Scenario 4)

Z20.828: Contact with and (suspected) exposure to other viral communicable diseases
(This code is for those with a KNOWN exposure- Scenario 3)

Expected Reimbursement/Insurance Payment for Testing (8)

U0001 – PCR Testing : $35.91
U0002 – Antibody Testing : $51.31

Note: The rates your commercial insurance will be billed for and will pay for these tests is variable, but they typically use these rates from the CMS (Medicare) in constructing their payment and reimbursement rates

CLICK TO EXPAND // References

About Rob Abbott, M.D.

Rob Abbott, M.D. is Autoimmune Wellness's resident Medical Advisor. He is medical director and the functional physician for Resilient Roots: Functional and Evolutionary Medicine in Charlottesville, Virginia. He completed his family medicine internship with VCU-Shenandoah Valley in Winchester Virginia and is a graduate of the University of Virginia (U.Va.) School of Medicine where he served as a student ambassador for the U.Va. School of Nursing’s Compassionate Care Initiative, promoting resilience, compassion and self-care. He has completed additional training with the Institute for Functional Medicine, is a Kresser Institute ADAPT Level 1 trained clinician, and is an AIP Certified Coach. Rob approaches medicine from an evolutionary and functional perspective and practices what he calls “spiritually focused and evolutionarily informed functional medicine.” In his free time, Rob enjoys creative expression through writing, sharing blogs, poetry and podcasts through his website amedicinalmind.com.

10 comments

  • Karen Sullivan says

    PCR testing only tells us if there is a fragment of the virus not if the person has been infected or if they have developed natural immunity. Suggesting this is the best way to test is inaccurate and misleading readers and can delay more accurate serology testing for our front care workers. I only reach out as a fan of your page so please accept this comment with the spirit of kindness it is sent to you with.

    • Hey Karen

      I appreciate your message, but am struggling to understand your statement.

      This is taken from the article

      “After the collection of these cells and their mixture into the testing medium, the lab would then perform a test known as a PCR (Polymerase Chain Reaction) to essentially look for evidence of the virus’ genetic material (it has RNA instead of our DNA) in the collected set of cells. As the virus replicates predominantly in tissues of the respiratory tract, finding evidence of its genetic material from cells in the respiratory tract in someone with symptoms most consistent with the best known symptom pattern of COVID-19 is arguably the best method of identifying someone who is sick with an active infection of COVID-19.”

      In this statement I clearly state the test is looking for genetic material and ,when in the context of all the qualifiers I listed, is arguably the best test for those with active symptoms as compared to serology tests that may be better after an acute infection when PCR tests may actually become negative.

      I am not sure I understand your statement or what is misleading in the article and I also am not sure I understand what you are referring to in regards to more accurate serology tests. Are you referring to the antibody tests I have described in the article? Most individuals are indeed performing antibody tests and then depending on the institution may then do PCR tests for certain individuals with positive antibody tests.

      I hope this has helped clarified things for you, but frankly I don’t fully understand your comment so am challenged to provide a helpful response.

  • Mallory McKay says

    Thanks so much for this information! Are you able to clarify for my non science brain- would an antibody test show (within the ranges of accuracy!) antibodies if you had had the virus and it was not still in an active phase? Like if you’d had it 8+ weeks ago? Or is it more about the present time if it shows up?

    • Hey Mallory

      Thanks for your message. So indeed the antibody tests that have the IgG antibody should still theoretically be positive at that duration of time after an infection

  • Julie Cinquina says

    Just wondering what happened to my comment?

    • Mickey Trescott says

      Hi Julie! Sometimes it takes us up to a week to approve comments, but I don’t see one for you on this post. Can you resubmit? Sorry for the trouble!

  • Patrick says

    Thank you for the article. Regarding this question:
    c) Is the antibody test actually showing evidence of an immune response to COVID-19 and not just another type of more benign coronavirus?
    This is my biggest concern. Without discerning between the 7 known coronaviruses, how confident can we be with a positive test result? Do you see a way of differentiating between them, making the tests more specific?
    Thank you.

    • Hey Patrick,

      Thanks for your message and this is a really good questions. Interestingly for all of the EUA’s the FDA has indicated labs must include this information, “Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.” The coronavirus strains are typically distinguished by variations in the 4 main proteins as well as the clinical syndrome associated. While most of the antibody tests I have reviewed have shown negative results towards other classes of viruses, I have not seen compelling data comparatively with other coronaviruses, but it does appear the N (Nucleocapsid) protein and S (Spike protein) and antibody tests directed at these proteins are the most sensitive and specific of the antibody tests available.

  • Richard Cook, MD says

    As you are probably aware, Labcorp came out with their antibody test last week and also have IgA. Interestingly, their antibodies are to the S-protein.

    • Thanks for the comment, yeah I thought it was funny I got their email the day after I finalized the piece, planning to make some updates shortly. I agree the chose of S protein was rather interesting. I was just reading where I believe Quest is actually now primarily using Abbott Labs’ (no affiliation lol) antibody test that has some compelling data on the package insert, but I have not been able to determine to which proteins the IgG antibodies are directed.

Leave a Comment