Smart Patients Get Smart Care™

The World’s Leading Authority for Chronic Lymphocytic Leukemia Patients

The CLL Nurse’s Note: Common Questions and Answers About the Most Recent COVID-19 Testing Recommendations

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

We have a lot to discuss, so let’s get started!

Right now, perhaps more than at any other point in the pandemic, testing early, testing often, and testing with the correct type of test are critically important. This is due to a couple of the biggest tools that were previously available in the COVID-19 toolbox no longer being options for either protection or for treatment.

This includes the pre-exposure prophylaxis monoclonal antibody Evusheld losing its ability to neutralize most all of the circulating variants in the US, as well as Bebtelovimab’s Emergency Use Authorization being paused for treatment. CLL Society encourages everyone to be aware that the 5-day timeclock is ticking and is of even more importance than ever before for those who have symptoms and need to quickly obtain one of the highly-effective oral antiviral treatments (such as Paxlovid or Molnupiravir). And for those who do not qualify to take the oral antivirals, the 7-day timeclock is ticking for receiving outpatient Remdesivir as soon as symptoms begin.

What Are the Differences Between the Two Types of COVID-19 Tests?

PCR Tests (Sometimes Called Molecular Tests): This type of test amplifies small amounts of the virus’s genetic material (DNA) by replicating it into larger amounts until it can be detected. This is performed using a technique called a polymerase chain reaction, hence the abbreviation PCR. 

A positive or negative PCR test more accurately reflects whether you are infected with the virus at the time of the test. The amplifying property of PCR technology allows the test to successfully detect even the smallest amount of coronavirus DNA that is present in a sample. This makes either a POSITIVE or a NEGATIVE test result highly sensitive, with an accuracy rate that approaches 100%. This makes PCR tests the gold standard for diagnosing.

PCR (molecular) tests are ideal for those who are pre-symptomatic, those who have had known exposure, or for those who are just beginning to have symptoms. The challenge with PCR tests has been the length of time required to find out if you are positive or negative. 

The average individual does not usually consider taking a COVID-19 test until they are 1-2 days into their symptoms. From that point, additional time may be required to find an available appointment at your local drugstore or doctor’s office depending upon availability. From the time the test is performed, an additional waiting period of 48-72 hours on average is necessary to obtain the test results. By that point, most people are already on day 3-4 of symptoms. This puts them at risk for being outside the 5-day window from symptom onset in which to qualify for oral antivirals (such as Paxlovid). Not to mention there will be additional time required from the point you receive the positive test result to contact your healthcare provider, receive a callback, be evaluated, and ultimately receive a prescription for COVID-19 treatment. This is why early testing as soon as you experience any symptoms is key, and it is important to never be dismissive of symptoms. 

Antigen Tests (Sometimes Called Rapid Tests): Antigens are substances that cause the body to produce an immune response by triggering the production of antibodies. The purpose of an antibody is to search for antigens and assist with attacking them so they can be destroyed by the immune system. 

The COVID-19 antigen tests are designed to mimic that same detection system by looking for those specific COVID-19 proteins (antigens) found on the surface of the virus by using lab-made antibodies in the testing solution which search for the COVID-19 antigens (proteins) produced from the virus. 

When a person is symptomatic with COVID-19, typically this will mean there is a higher amount of virus in their system (sometimes called viral load). Antigen tests can more easily detect these proteins when there are more of them available to detect. So, results of tests performed in individuals who are further into the course of their infection are oftentimes found to be more accurate. However, unlike molecular PCR tests, antigen tests don’t have the ability to amplify (or replicate) the one tiny thing they are looking for. There must be a high enough amount of viral antigens (proteins) within the sample for the lab-made antibody solution on the test strip to generate a positive test result. When a person is in the early days of COVID-19 infection, there is typically a lower amount of virus present in the nose from which the samples are taken. If there is not a high enough amount of the virus present, this is why antigen tests often miss early cases of COVID-19.

When someone has a POSITIVE antigen test result, this means they are very likely to be infected and the test is more accurate. However, antigen tests have a very high propensity for a FALSE NEGATIVE test result!

In November 2022, the FDA updated its guidance on how to properly perform home antigen COVID-19 tests. Now, if you are experiencing any symptoms of COVID-19 and receive a negative at-home antigen test result, you should still continue to isolate until you can obtain a PCR test and/or keep repeating the antigen tests every 48 hours until you have taken at least three of them in a row

A negative antigen test result only means it may be too early to detect the COVID-19 proteins and you could very well just have an undetectable viral load at the time the test was performed. Therefore, rapid antigen tests should not be the gold standard for diagnosing COVID-19, even though this is exactly what has become the norm for individuals in the US due these types of tests being more convenient and being made readily available to the general public in 2022. 

These at-home antigen tests are, however, an excellent tool for individuals to use after they have a confirmed COVID-19 diagnosis to determine whether or not they are still shedding the virus and are still considered infectious (more on that later).

When Should a Certain Type of Test Not Be Used?

PCR (molecular) tests should not be used to determine how long you are still infectious after a confirmed diagnosis of COVID-19 has been made. Again, this is because PCR tests are designed to duplicate even the smallest amounts of viral DNA until they are made detectable, which makes them highly sensitive. Even those who are immunocompetent can continue to receive a positive PCR test for weeks after being infected with COVID-19. But this does not mean they are still shedding enough of the virus to be infectious to others!

As mentioned above, antigen tests should not be considered a reliable tool for diagnosing COVID-19, especially in those who are not symptomatic or early on in their infection. 

What Type of COVID-19 Test is the Most Reliable?

Without a doubt, the most reliable is going to be the PCR test. You can trust either a positive or a negative PCR test result because it is more sensitive in detecting any small amount of viral DNA that is present within the nasal cavity.

Is There an Option for At Home Rapid PCR Tests?

Until mid-November 2022, at home rapid PCR tests have not been available to the general public. However, a number of them have recently received FDA Emergency Use Authorization (EUA) and have become available online either through direct mail-order from the company itself or through Amazon.

The FDA has a comprehensive list of all the EUA tests (both antigen and PCR) that you can find here. When looking specifically for at-home PCR tests from their website, you are looking for the key words “molecular test” as opposed to antigen test. At the time this article was written, we are unaware of any local stores or pharmacies that are carrying at home rapid PCR tests. But Lucira Check-It COVID-19 Test Kits are available for purchase on Amazon).

If you will be seeking insurance company reimbursement for at-home PCR quality tests, we would encourage you to call your insurance company ahead of time to discuss their reimbursement policy for COVID-19 home test kits.

Are Antigen Tests Ever a Good Tool for Testing?

Yes, absolutely. They are of particular importance for determining when an individual is no longer shedding the virus AFTER a diagnosis of COVID-19 has been confirmed. With each new variant there has been a variation in how long individuals remain infectious, sometimes for as little as 4 days and sometimes up to 14 days. The CDC’s most recent set of guidelines no longer recommends testing to determine if you are still infectious, but instead the guidelines rely on everyone wearing a quality well-fitted mask through day ten of symptoms. However, we know in reality that mask-wearing has not been happening as a general rule for the public.

CLL Society still believes it is an excellent practice for individuals with CLL / SLL who have a confirmed COVID-19 diagnosis to perform antigen testing when symptoms are noticeably improving. If your antigen test is still positive, then wait 48 hours to test again. You can still consider yourself infectious until you have received TWO CONSECUTIVE negative antigen tests that were taken 24 hours apart. It is important to understand that immunocompromised individuals can continue to test positive for weeks, or even months, due to their immune systems having a difficult time clearing the virus from their body effectively. If you are still testing positive for COVID-19 with an antigen test for 14 days or longer from symptom onset, it is recommended by the CDC that you consult with an infectious disease specialist. 

Whenever using a COVID-19 antigen test as a method of determining if you are infected with COVID-19 (preferably you should use a PCR test instead), you should always repeat testing at least two more times following a negative test result whether you still have symptoms or not. If you have a negative antigen test result, it is recommended to then test again 48 hours after the initial negative test, and then test a third time 48 hours after the second negative test. This means you should have a minimum of three negative antigen tests to indicate you have tested negative for COVID-19. You can read more on the antigen test recommendations from the FDA here.

My Antigen Tests Have Expired, Can I Still Take Them?

Perhaps. Typically, the recommendation is to not use COVID-19 tests that are beyond the expiration date printed on the box. However, the FDA has extended many of the expiration dates for these home test products after rigorous testing to ensure they can remain accurate for a longer period of time. 

You can find more information at this FDA link on the extensions. Scroll down to the middle of the page where there is a table that lists out the different tests that have received EUA. Find the manufacturer and name of your test kit, then on the far right under the “Expiration Date Column” click on the blue hyperlink which will take you to the list of updated expiration dates for that brand. You will need to have the lot number on your test kit handy to determine whether or not your kit’s expiration date has been extended.

Can I Report My Home COVID-19 Test Results?

The answer is yes, and please do. Since the emergence of the original Omicron variant in November 2021 when home antigen tests became more widely available (and affordable), reported case numbers suddenly became drastically underreported. Many scientists believe cases have been underreported to health departments by as much as 5-10 times the actual case numbers, mainly due to unreported at-home testing and many individuals no longer testing at all when they have symptoms. This fact has been confirmed with wastewater data becoming more widely available, which you can read more about and see graphics for in our Weekly COVID-19 Updates

Recently, the US Government started an online anonymous self-reporting system through the National Institutes of Health (NIH) in hopes that the public will voluntarily participate to help everyone better gauge the level of community spread. COVID-19 test results provide valuable data that public health departments and individuals can use to assess the current level of risk and modify public health responses on the local community level, the state level, or nationwide. This program is called It takes less than 30 seconds to self-report, and individuals are encouraged to report EITHER a positive or negative test result.

We realize this has been a lot to digest at one time. But we hope the above information on testing has been educational, insightful, and will become another valuable COVID-19 resource to our community.

Keep learning and stay well.

Robyn Brumble, MSN, RN
Director of Scientific Affairs & Research
CLL Society

CLL Society - COVID-19

When appropriate, the CLL Society will be posting updates and background information on the present Coronavirus pandemic focusing on reliable primary sources of information and avoiding most of the news that is not directly from reliable medical experts or government and world health agencies.