Excerpt originated from Urgent Caring Vol 04, Issue 5 (e-Newsletter of the College of Urgent Care Medicine, offering free monthly CME) - Last updated 7/6/2020

Author: Christopher Chao, MD

Please note: This is a rapidly evolving and developing situation, so please refer to the Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and your local health department for the most up to date information

Testing for COVID-19 has been a hot topic lately, with widely conflicting “advice” circulating among government agencies, health care providers and the general media. Unfortunately, there is significant anxiety among the general populace, and patients are calling urgent care clinics asking about the availability of COVID testing. Testing availability varies by geographical location, as there are states where anyone can get tested, and other states where testing requires a provider order or patients need to meet specific clinical criteria before testing is performed.

Here are some key points with regards to COVID-19 testing:

1) SARS-CoV-2 is the virus, and COVID-19 is the disease. Technically, you are not testing for COVID-19. You are testing for presence of the virus, SARS-CoV-2, or antibodies to SARS-CoV-2.

2) Current testing is performed under an emergency use authorization (EUA) issued by the FDA which grants the use of a product in times of a national emergency. There are tests in the marketplace, mostly antibody testing that do not have an FDA emergency use authorization, and those tests should not be used.

3) There are 2 types of testing: a molecular test (testing for the presence of some component of the SARS-CoV-2 virus) and antibody testing (testing for the presence of antibodies made by the body to fight SARS-CoV-2 infection)
- Molecular (PCR and antigen) detection tests utilize technology to detect the presence of SARS-CoV-2 virus, either through detection of nucleic acid utilizing NAAT/PCR or antigen/viral capsid proteins.
- Antibody tests detect antibodies that the body produces in response to an infection. In COVID-19, the body will produce IgM and IgG antibodies against SARS-CoV-2 which may help fight off the infection.

4) While the manufacturers report test sensitivity up to 98%, there is concern that the sensitivities of some tests may be overestimated. The higher the sensitivity, the more “accurate” the tests. If sensitivity is overestimated, there will be more false negatives than expected. Accuracy also varies depending on quality of sample collection and stage or illness.

Of the viral detection tests, RT-PCR (reverse transcriptase Polymerase Chain Reaction) has the highest sensitivity and is the current gold standard. The drawback of the RT-PCR test is run-time, which may require up to several hours, although multiple samples may be run simultaneously. Mobile platform Point of Care (POC) tests can deliver “real time” results in 5-30 minutes, are portable and may be used in an ambulatory clinic setting.  The downside of mobile platform point of care testing is that only one sample may be run at one time. Because antigen tests have lower sensitivity compared to nucleic acid tests, a negative test may should be reflexed to a RT-PCR test.

5) Testing is not an unlimited resource! Although testing capacity in the United States has greatly expanded lately, clinicians in regions and states experiencing a surge in cases have reported delays in receiving results due to shortage of testing reagents and testing supplies. Testing sites have a functional limit of the number of tests that can be performed due to staffing and PPE. Not every patient that walks through the door needs to be tested for COVID-19. It is important to understand the role and limitation of the tests so that the tests can be ordered appropriately and to prevent overload on a stressed system.

Choosing the right test:

A COVID-19 viral diagnostic test is appropriate for:

• individuals with signs or symptoms consistent with COVID-19
• asymptomatic individuals with recent known or suspected exposure to SARS-CoV-2 to control transmission
• asymptomatic individuals without known or suspected exposure to SARS-CoV-2 for early identification in special settings
• individuals being tested to determine resolution of infection, and individuals being tested for purposes of public health surveillance for SARS-CoV-2.

CDC defines close contact as “someone who was within 6 feet of an infected person for at least 15 minutes starting from 2 days before illness onset (or, for asymptomatic patients, 2 days prior to specimen collection) until the time the patient is isolated.” A patient who is asymptomatic and does not have suspected exposure does not need COVID-19 testing.
Source: Overview of Testing for SARS-CoV-2, CDC Updated July 2, 2020

The test is positive if the SARS-CoV-2 virus is detected either by detecting nucleic acid or viral proteins.

Limitations:

• None of the tests are 100% sensitive, and false negative results may be reported. Consider the pre-test risk. A negative COVID-19 viral test in a patient who has high pre-test probability (i.e. is febrile, reports sore throat, cough, loss of taste and smell who has confirmed exposure) does not rule out COVID-19. Even with a negative test, the patient should still be isolated per CDC guidelines.
• Testing too early after exposure may result in a negative test result due to insufficient viral load for detection. Studies suggest waiting 3 to 5 days after suspected exposure to test an asymptomatic patient to allow sufficient viral load for detection.  
• Studies suggest that SARS-CoV-2 may be detected for up to 30 days in patients; such detection of SARS-CoV-2 may occur after a patient has recovered, and the patient is no longer contagious. This is a potential limitation of the CDC test-based strategy return to work criteria.

The COVID-19 antibody test detects antibodies that the body produces to identify SARS-CoV-2 virus.

Because antibodies take time to develop in response to infection, antibody detection cannot be used to determine active infection. While antibodies may be present in a few days after initial infection, it may take days to weeks before antibodies are detectable. There is also no data on how long IgG or IgM antibodies persist or whether the presence of antibodies provides immunity.

Limitations:

• Antibody tests should not be used as the sole basis to diagnose of exclude SARS-CoV-2 infection or to inform infection status.
• Antibodies may take several days to weeks to develop, so a negative test does not rule out active disease
• Positive antibody test results may be due to past or present infection with non-SARS-CoV-2 coronavirus such as coronavirus HKU1, NL63, OC43, or 229E
• Positive antibody test results do not indicate that a patient is immune or cannot be re-infected.

Take home points:

• Document and assess the patient pre-test risk. Proper interpretation of COVID-19 test results and clinical guidance is heavily dependent on the pre-test risk.
• Testing is not an unlimited resource and not all patients who request testing need COVID-19 testing
• Counseling the patient after results are finalized will minimize patient misunderstanding of the results.

The following language may be used for patients and non-health care professionals to explain the role of SARS-CoV-2 antibody testing:

Recently, there has been much buzz in the media about a test that can “tell you if you have had COVID-19 infection.” The test that the media is referring to is called an antibody test. An antibody test is different from the COVID-19 test in that it detects antibodies that your body makes to identify the virus that causes COVID-19. Unfortunately, interpretation of the test is not as simple as black or white.

Antibodies are produced by the body to fight off infection. IgM antibodies are produced initially, and IgG antibodies are produced later, which are often associated with long-term immunity. The commercial tests produced by LabCorp, Quest Laboratories, etc. are designed to detect antibodies including IgA, IgM and IgG that are specific to SARS-CoV-2 (the virus that causes COVID-19).

At this time, we do not know a lot about SARS-CoV-2, nor do we know the exact timing of antibody production or if antibody production conveys any immunity, short or long-term. A recent study has suggested that COVID-19 specific antibodies are short-lived, and most patients lose detectable antibody levels within 3 months post-infection. Thus, a NEGATIVE test does not necessarily rule out a recent COVID-19 infection. It is possible that your body did not produce detectable antibodies, or the antibodies that your body produced have decreased (antibody production may decrease with time), or not enough time has elapsed since the initial infection that your body has produced sufficient antibodies.

Depending on quality of the test, a POSITIVE test does not indicate that you have had COVID-19. It is possible that antibodies against non-SARS-CoV-2 coronavirus or other viruses may cross-react with the test, causing a false positive result.

We also do not know whether IgG antibodies will provide any immunity against COVID-19 and whether it will provide protection against future infections. Therefore, even if your antibody test is POSITIVE, you are still encouraged to follow social distancing guidelines and good personal hygiene.