In response to inquiries about Covid-19 testing, we are sharing current recommendations and available options. Note that this article was written on May 6, 2020 and that given the rapid changes as we gather more information, this information may be quickly outdated. For most up to date information, refer to the CDC website, your local Health Department and your qualified healthcare provider.
DEFINITIONS:
Covid-19 is the illness caused by the strain of coronavirus SARS-CoV-2. We have now seen that people infected with this virus may have a range of symptoms. They may be completely asymptomatic, or have a mild to severe respiratory illness. The most common symptoms include fever, cough, difficulty breathing, fatigue, muscle aches, sore throat, but can also include symptoms such as loss of taste or smell, gastrointestinal illness, or neurological symptoms.
WHAT TESTS ARE AVAILABLE FOR COVID-19?
There are tests that look at whether the actual virus, SARS-CoV-2 is present in the body (molecular or PCR testing), and there are tests that look at whether your body has mounted an immune response against the virus (antibody or serology testing).
WHAT IS ANTIBODY (SEROLOGY) TESTING?
Antibody tests may test for IgG and/or IgM antibodies. Antibodies are glycoproteins produced by your white blood cells that are used by your immune system to fight off infections. Antibody tests are commonly used to detect prior infections or immunity developed from vaccines (e.g., you may have had your MMR antibody titer checked to see if you have immunity against measles, mumps or rubella, or Hepatitis A antibody testing, to check if you have had Hepatitis A or mounted an immune response to a vaccine against it).
In the case of Covid-19, presence of IgG antibodies in a blood sample against SARS-CoV-2 suggests a prior infection, but does not exclude a current infection or recently infected patients who are still contagious, especially if IgM antibodies are also detected (IgM antibodies typically start to decline approximately one month after the onset of infection, but more studies are needed to better understand this in Covid-19). IgM antibodies suggest a current or recent infection, while IgG antibodies generally do not begin to appear until 7-10 days after infection and tend to be longer lasting.
It is unknown how long IgM or IgG antibodies to SARS-CoV-2 will remain present in the body after infection. We also don’t know whether the presence of these antibodies confers immunity from a future infection, the amount of antibodies needed to offer protection, and if there is immunity, how long this immunity lasts. Research is currently underway to answer these questions.
Furthermore, results for IgM and IgG antibodies may be falsely positive or falsely negative (more on this below). Laboratory test results should always be considered in the context of clinical observations and epidemiological data in making a final diagnosis and patient management decisions. A qualified healthcare professional should interpret results and explain them to the patient.
Sources:
https://www.cdc.gov/coronavirus/2019-ncov/lab/serology-testing.html
http://sonoranhealth.org/resources/IgM+vs+IgG+antibodies+in+Serologic+Testing+$282008$29.pdf
https://www.fda.gov/media/136623/download
WHAT ARE THE BENEFITS OF ANTIBODY TESTING?
A positive antibody test that is appropriately validated and is specific to SARS-CoV-2 virus, suggests that a patient has had a past or current Covid-19 infection. The test can also be useful on a population level and help us better understand how many people have developed this immune response to the virus.
As we continue to study SARS-CoV-2 and our immune response to this virus, we will gain a better understanding of whether individuals who have developed an adaptive immune response (have the positive antibodies) are less susceptible to future infection. It will also be helpful to know how long these antibodies will be detectable following infection. This test can also help identify individuals who may be eligible to donate their “convalescent plasma”, which is being investigated as a treatment to those who have severe symptoms of Covid-19.
WHAT ARE THE LIMITATIONS OF TESTING?
Currently, the tests that are on the market vary in accuracy. Some report to have accuracy >99% while others report lower numbers. Furthermore, only a small percentage of tests that are on the market have been granted the Emergency Use Authorization (EUA) by the FDA (more on this below) – only 12 antibody tests are listed on the FDA’s website to have EUA on May 6, 2020 (from over 150 tests that are reported to be on the market at this time!). After this emergency status has ended, these tests will not be able to continue to be used, unless they have FDA approval.
Let’s address accuracy and implications of falsely positive or falsely negative tests:
These tests are not meant to serve as diagnostic tools at this time, given that they are new, and have not been sufficiently studied. For instance, let’s say you had another strain of coronavirus several years ago, and still have antibodies against that strain. Let’s say you did not have Covid-19. You take the test and it’s positive because your antibodies against the other coronavirus strain are being detected and falsely identified as SARS-CoV-2 antibodies. This is called a false positive test – the test indicates that you had the SARS-CoV-2 infection, but you didn’t. This gives you a false reassurance that you’ve had Covid-19.
Note that 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.
What if you get a false negative result? In this scenario, you’ve had the SARS-CoV-2 infection, but when you test for antibodies, you get a falsely negative result.
Why does this occur?
There can be several reasons.
A negative serologic result may mean that the person hasn’t developed antibodies in sufficient quantities at the time of testing. It could also be that the testing was done too early in the course of Covid-19, while the amount of antibodies is still going up. It could also be that the patient is lacking an adequate immune response (e.g., due to being on immunosuppressant medications).
The above two examples are both reasons to select the test with the greatest sensitivity and specificity, but also to interpret these results very cautiously while we are gathering more reliable, larger data sets to confidently interpret the results. It is also important to discuss the results with a healthcare professional who can take into account the context of your situation, exposures and any symptoms, as well as the timeline, and use clinical judgment when discussing the meaning of the results.
It should be noted that according to CDC recommendations, antibody testing should not be used to diagnose acute infection. Negative results do not rule out SARS-CoV-2 infection, especially in those who have been in contact with the virus. Follow up molecular testing (the presence of the actual virus is being tested) should be employed to diagnose an acute infection.
Source: https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html
IS THERE A FINGER STICK ANTIBODY TEST I CAN COLLECT AND PROCESS AT HOME?
Although there are tests like this on the market, at the time this is written (May 6, 2020), the FDA has not issued any EUA’s to at home serology tests, and these are not felt to be as accurate at this time. This is an area of great interest, given that if and when such a test gains approval or EUA, individuals would not have to go to testing centers or doctor’s offices to obtain the test, and would therefore minimize their exposure and need for use of PPE for the purpose of performing the test.
WHAT IS MOLECULAR TESTING?
A molecular test detects the presence of genetic material of SARS-CoV-2, and if present, indicates a current infection. This can be found in upper respiratory tract specimens. These include nasopharyngeal specimen (collected from the back of your nose by a healthcare professional), an oropharyngeal specimen, nasal swab, or a nasopharyngeal/nasal wash/aspirate. For more information on how these are collected and where they are collected from, go to CDC website.
WHAT ARE CURRENT RECOMMENDATIONS REGARDING TESTING?
CDC: Check the CDC website for guidance on who should be tested https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/testing.html. If you think that you may need to be tested or are not sure whether you should be tested, contact your qualified healthcare provider.
Here is the current prioritization sequence for testing, by the CDC: https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html
From the CDC website:
PRIORITIES FOR COVID-19 TESTING (Nucleic Acid or Antigen):
High Priority
- Hospitalized patients with symptoms
- Healthcare facility workers, workers in congregate living settings, and first responders with symptoms
- Residents in long-term care facilities or other congregate living settings, including prisons and shelters, with symptoms
Priority
- Persons with symptoms of potential COVID-19 infection, including: fever, cough, shortness of breath, chills, muscle pain, new loss of taste or smell, vomiting or diarrhea, and/or sore throat.
- Persons without symptoms who are prioritized by health departments or clinicians, for any reason, including but not limited to: public health monitoring, sentinel surveillance, or screening of other asymptomatic individuals according to state and local plans.
New York State Department Of Health recommendations:
As New York state continues to expand its capacity to test, it is recommended that testing be prioritized the following way:
Testing shall be authorized by a health care provider when:
- An individual is symptomatic or has a history of symptoms of COVID-19 (e.g. fever, cough, and/or trouble breathing), particularly if the individual is 70 years of age or older, the individual has a compromised immune system, or the individual has an underlying health condition; or
- An individual has had close (i.e. within six feet) or proximate contact with a person known to be positive with COVID-19; or
- An individual is subject to a precautionary or mandatory quarantine; or
- An individual is employed as a health care worker, first responder, or other essential worker who directly interacts with the public while working; or
- An individual presents with a case where the facts and circumstances – as determined by the treating clinician in consultation with state or local department of health officials – warrant testing.
Bottom line: after discussing your symptoms with your clinician, your clinician will use her or his clinical judgement and epidemiologic factors to counsel you regarding testing and treatment. It’s important not to forget to test for other causes of respiratory illness.
WHAT TEST CAN I TRUST FOR SEROLOGY/ANTIBODY TESTING?
There are a number of tests available, and many of them do not have the EUA (emergency use authorization) by the FDA, as discussed above. Even the tests that do have the EUA are not approved by the FDA after the emergency circumstances end. They have met the requirements for EUA given the current circumstances, but will still need review by the FDA before approval.
That being said, in analyzing the tests that are available in NYC, we identified options for antibody testing that we feel most comfortable with based on the issuance of EUA by the FDA as well as sensitivity and specificity reports.
If you are interested in getting the antibody test due to prior exposure to SARS-CoV2 (>14 days after exposure), or due to symptoms that were highly suspicious for Covid-19, but were never confirmed, antibody testing may be a reasonable option at this time. Always consult your healthcare provider before getting the test done.
From the FDA website:
What are the known and potential risks and benefits of the test?
Potential risks include:
- Possible discomfort or other complications that can happen during sample collection.
- Possible incorrect test result (see below for more information)
Potential benefits include:
- The results, along with other information, can help your healthcare provider make informed recommendations about your care.
- The results of this test may help limit the spread of COVID-19 to your family and others in your community.
WHAT IS FDA’S EUA AND WHY IS IT IMPORTANT?
EUA stands for Emergency Use Authorization. FDA EUA means that the FDA has performed a review of validation data and have found it to be acceptable.
On the basis of the February 4, 2020 HHS EUA determination, the Secretary of HHS then declared that circumstances exist justifying the authorization of the emergency use of in vitro diagnostics for detection and/or diagnosis of the novel coronavirus (2019-nCoV) subject to the terms of any authorization issued under section 564(a) of the Act.
On February 29, 2020, the FDA issued an immediately in effect guidance with policy specific to this public health emergency. This guidance was updated on March 16, 2020 and again on May 4, 2020.
CDC has granted a right of reference to the performance data contained in CDC’s EUA request (FDA submission number EUA200001) to any entity seeking an FDA EUA for a COVID-19 diagnostic device.
Here is a table of diagnostic tests that currently have the Emergency Use Authorization by the FDA:
Here are some of the testing options to consider that have the FDA’s EUA and have reported high sensitivity and specificity.
Quest (uses Abbott Labs which has FDA’s EUA) – available at Quest draw stations:
Sensitivity/Positive percentage agreement of Abbott Labs serology tests at 14 or more days after symptom onset: 100% (meaning that all of the specimens from individuals that tested positive for SARS-CoV-2 were positive for serology).
Specificity/Negative percentage agreement of DiaSorin serology tests: 99.63% (meaning that out of all of the specimens from individuals that did not have Covid-19, 99.63% tested negative by serology).
Empire City Labs (uses Roche molecular (PCR) testing, DiaSorin serology testing and Euroimmun, which also have FDA’s EUA).
Negative percentage agreement of Roche PCR tests: 100% (nasopharyngeal swab collected by a qualified professional)
Positive percentage agreement of Roche PCR tests: 100% (nasopharyngeal swab collected by a qualified professional)
Day 15 or more after diagnosis:
Positive percentage agreement of DiaSorin tests: 97.6% (97.4%)
Negative percentage agreement of DiaSorin tests: 99.3% (98.5%)
Day 21 or more after onset of symptoms:
Positive percentage agreement of Euroimmun tests: 93.8%
Negative percentage agreement of Euroimmun tests: 99.6%
Empire City Labs phlebotomists will come to your home (in the NYC area) in PPE (they change PPE between each patient). Their phlebotomists may also be able to visit locations in the Hamptons (an extra charge may apply), and some are authorized to perform nasopharyngeal swabs when indicated.
Roche test has just recently been issued FDA’s EUA on May 2, 2020 (we are in the process of looking into where and when this testing will be available in NYC):
Positive percentage agreement of Roche serology tests at 14 or more days after PCR confirmation of SARS-CoV-2: 100%
Negative percentage agreement of Roche serology tests: 99.81%
ARE THESE TESTS FDA APPROVED OR CLEARED?
FROM THE FDA WEBSITE:
No. These tests are not yet approved or cleared by the United States FDA. When there are no FDA-approved or cleared tests available, and other criteria are met, FDA can make tests available under an emergency access mechanism called an Emergency Use Authorization (EUA). The EUA will remain in effect (i.e., the tests granted the EUA can be used) for the duration of the Covid-19 declaration justifying emergency of In Vitro Diagnostics (lab tests), unless it is terminated or revoked by FDA. Once terminated or revoked by the FDA, the tests may no longer be used.