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We need accurate, sensitive, specific testing for the virus that causes COVID-19 to help us understand the disease, figure out who has really been affected, and its outcome. And maybe it could be used to safely resume “business as usual,” or at least business near-usual.

COVID-19 testing falls into two main categories so far: diagnostic tests to tell you if you have COVID-19 now and tests to tell you if you already had it. Read on for more about COVID-19 testing, pitfalls, and pointers.

There are a number of reasons why we should all want widespread, high-quality testing for everyone:

• It’s a major way that South Korea and Germany squashed their coronavirus outbreaks.
• Many Americans who needed testing, never got it.
• Some people had COVID-19, but the diagnostic test was negative (known as a false negative).
• People with mild illness were never tested.
• Some people with coronavirus never showed symptoms and were not tested.
• Surprisingly high amounts of the US population may have already had coronavirus, early studies suggest.

A test that could help decipher if a person was exposed, immune, or contagious could help protect vulnerable populations and could conceivably help us safely resume normal life.

If someone already was sick and is feeling okay now, what’s the use of testing them for coronavirus after the fact?

There is one really big reason: immunity. Our immune systems are designed to detect invaders and destroy them. But it doesn’t stop there. Our immune systems also make sure that the invader cannot come back again any time soon.

The immune system can therefore “remember” who the bad guys are and make sure they don’t come back again. How’s that for genius?!

When we get SARS-CoV-2, we develop immune proteins called antibodies. We might develop IgM, IgA, and IgG antibodies to the virus. Antibodies help to kill off a virus and get rid of the infection. They also help to protect you from getting reinfected. Antibodies can destroy the virus or they can bind to the virus and block it from attacking your cells. The anti-infection properties are so powerful that there are studies underway to find out if blood from recovered COVID-19 infection can be used to treat the disease. Vaccines prompt our bodies to make these very same antibodies- without having the full-fledged illness.

Immunity means people who already have had the virus can’t get it again for months to years (maybe more). Theoretically, they could frolic around in society because they are already protected from COVID-19. Grocery stores? Public restrooms? No worries! Masks and gloves? Who needs ‘em? They don’t have to worry about getting coronavirus again. And they can’t spread it to others, either. We discuss immunity further in “Blood Antibody Tests for Past COVID-19,” below.

On the other hand, everyone who lacks immunity to the virus is still vulnerable to get it and spread it. Those over 65 years old or with underlying conditions would still be in significant danger.

Coronavirus infections and immunity may be far more widespread than previously believed, even 50 –85 times higher. Initial estimates of past coronavirus infections are: 25% of people in New York City, 32% in Chelsea, Massachusettes, between 2.8 and 5.8% in Los Angeles County, and 2.8% in Santa Clara county, California. These numbers far exceed official case counts and suggest that our population has been building immunity all along.

If you’re like me, the future seems hopeful when thinking about how we could reopen society, especially for people who are immune to the virus. We could have return-to-work permits based on immune status. People who already have immunity to the virus would be the right people to put in healthcare settings. They would be the right ones to put in face-to-face business operations. They would be the right ones to put in contact with the most vulnerable groups– elderly or the sick.

So, let’s get into the nitty gritty. With all of the tremendous potential that testing holds for us, it isn’t anywhere near perfect. So here are some things you need to know when choosing the best COVID-19 test.

Do I Have COVID-19 Right Now?

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Respiratory Tests for Current Infection

Right now, the very best diagnostic test for SARS-CoV-2 is an upper respiratory nasopharyngeal (NP) swab that detects the virus’ RNA.¹ When you have a virus like coronavirus, it will replicate in your throat, nose, mouth, and lungs. This test measures the amount of virus in the back of your nose, where it joins with your throat.

The method for detecting coronavirus RNA is called real time reverse transcriptase polymerase chain reaction (rRT-PCR). PCR is a cutting-edge molecular technology that makes many copies of, and measures, a specific genetic signature. PCR has revolutionized science especially when measuring small amounts of bacteria, viruses, or other microorganisms. Since SARS-CoV-2 doesn’t have DNA, the test measures its RNA.

There may be up to 30% false negative results with coronavirus diagnostic NP swab tests.  That means someone with COVID-19 might be missed and could go on spreading it unknowingly.

Here are the main reasons why NP swab tests can miss COVID-19 infection:²

• The specimen wasn’t collected from the right place.
• It wasn’t collected at the right time.
• They didn’t collect enough material.
• Errors with handling, transport, or storage of specimens.
• Interfering substances or contamination.
• Poorly performed molecular assays.

Most false negative results are due to collection, handling, and transport.

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Location Matters: The Best Sample For an Accurate Coronavirus Diagnostic Test

Coronavirus infects the nose, throat, and lungs. Therefore, collecting a specimen from those sites makes good sense. Most experts agree that the NP swab is the best and the most practical. If the NP swab was collected correctly, it should be placed so deep in the nose that it will bring tears and cause the person to flinch.¹ Specimens collected from the back of the throat (oropharynx) are not as good.¹ The best sample would be collected from both upper and lower respiratory tract. That would include phlegm from a deep cough and bronchoalveolar lavage fluid (BAL). BAL is collected when a tube is inserted into the lung and saline fluid washes the lung and is analyzed afterward for coronavirus. Neither of these methods is very safe right now for healthcare workers, since it could release more virus into the air.¹

The Best Time For the Diagnostic Test

For most people, it’s best to collect for the NP swab test within the 1^st few days of symptoms.¹ However, that doesn’t work for everyone. If the virus isn’t replicating in the nose early on, the test could miss the infection. To account for that, if your first NP swab is normal, it may be good to test a second time, roughly 7-10 days after your symptoms began.

Two negative diagnostic NP swabs collected 24+ hours apart suggest that you are free of the virus and are considered safe to be around others.

Did I Already Have COVID-19?

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Blood Antibody Tests for Past Infection

You can find out if you have had coronavirus using a blood antibodies test. Tests are available now that test for IgA, IgM, IgG antibodies to SARS-CoV-2. The best one available right now is IgG antibodies. They indicate a long-term immune response to a virus. If you have IgG antibodies to SARS-CoV-2, then you may have already had coronavirus.

Blood antibody tests are not diagnostic tests. And they can’t tell you if you are protected from reinfection. But experts say that combining blood antibodies with the NP diagnostic swab dramatically improves diagnosis of COVID-19.^1,3-5 It especially helps out with false negatives from the NP swab test.¹

Blood antibody testing is legit. BUT, there is much debate about which antibody test is the best. Since blood antibody testing for COVID-19 is new, and tests are being released to market very quickly, they are not as accurate as we would like.⁶ A false positive, or a positive test result on someone who didn’t actually have protective blood antibodies, could mislead a person into thinking they were safe and taking undue risks with coronavirus.

Photo by National Cancer Institute on Unsplash

There are a number of naysayers when it comes to blood antibody testing. Some say having antibodies to SARS-CoV-2 might not actually protect you from reinfection. That’s because protection from SARS-CoV-2 depends on neutralizing antibodies, which are believed to be responsible for blocking the virus from entering cells. We are still learning about neutralizing antibodies when it comes to coronavirus. But one study showed that 70% of people who recovered from mild COVID-19 had neutralizing antibodies when they returned to the hospital for follow-up. Immune system working well? Check!

We don’t know everything about this virus and we won’t for decades. However, based on  generally accepted immunology principles, we DO develop immunity to viruses. Our antibodies destroy viruses and protect us from getting reinfected. COVID-19 patients do develop blood antibodies⁵ and neutralizing antibodies. And its close cousin, SARS-CoV (which caused the SARS global epidemic), boosted blood antibody protection for years after the infection.⁷ So even though we don’t know everything yet, we have to make some educated assumptions until we find out otherwise.

Select the Best Blood Antibody Test by Following These Guidelines:

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• Collect at the right time
• Measure IgG antibodies
• Choose an ELISA test targeting one or more coronavirus proteins
• Blood draw
• Have the test run at a CLIA certified, qualified, and experienced laboratory
• Check to make sure the assay is FDA cleared under emergency authorization
• Trust a test kit from a manufacturer with a proven track record of making in vitro diagnostic tests

Timing is still a HUGE issue with antibody tests, just like with the NP swab test. Do not run a blood antibodies test in the first week of coronavirus symptoms. That’s because your immune system may not ramp up antibodies until 7 or more days after symptoms. The best sampling time for blood IgM antibodies appears to be 2-3 weeks after the onset of symptoms.⁵ The best sampling time for blood IgG antibodies appears to be 3 to 7 weeks after symptoms and beyond.⁵ Because IgG antibodies indicate long-term immune response, they may be elevated for several months, or more, after initial symptoms. IgG antibodies are the most important kind of antibody test to get.

An ELISA (enzyme-linked immunosorbent assay) test is generally considered to be the best, most accurate test for measuring antibodies. Lateral flow immunoassays, similar to home pregnancy tests, are fast but lack the sensitivity and specificity of an ELISA assay. Your immune system may make antibodies against a few different coronavirus proteins. These include the spike, the envelope, the membrane, and the nucleocapsid. Ask your doctor, or research yourself, what protein is being targeted by the test. If it targets more than one, that’s even better.

Photo by National Cancer Institute on Unsplash

Generally speaking, a test that requires a blood draw and is processed at a CLIA certified, qualified, and experienced laboratory is much more trustworthy than a finger prick test done at home. Getting a blood draw means you will need to get your doctor’s authorization in many states. Research the laboratory- is it reputable?

Learn about the assay. Was it created from scratch or do they use a test kit? Was it passed by FDA for emergency use authorization? How many people have been tested with the assay? How sensitive and specific is the assay? That means how low does the assay accurately measure and how well does it measure what it says it does. If you can get this information, then you are working with a lab that wants to deliver an accurate and meaningful result. In the next year or two, we will have narrowed down the best tests with the best clinical sensitivity and specificity. Clinical sensitivity and specificity tells you how well the test accurately detects people who truly have COVID-19 versus those who don’t. But until then, remember, this is all very new and everyone -including laboratories- are still learning.

Stool

Some companies are measuring SARS-CoV-2 in stool specimens to tell about recent or past COVID-19. The virus has been detected in stool specimens up to five weeks after respiratory symptoms go away. While not diagnostic, this test can tell if someone has had coronavirus recently or if they are still carrying it. It may help with monitoring illness and prevent transmitting it in nursing homes. It’s great for children or the elderly because it’s easy and painless to collect a stool specimen.

There Is Much We Don’t Know, But We Still Have to Move Forward

We are in the wild west of testing in the brand-new frontier of COVID-19. No test has had months of research and development or validation. No lab has had years to refine and perfect its test. Tests were rushed through emergency authorization with FDA. That means one test is not enough. You might need to repeat a test. You need to run tests from different labs to confirm the findings.

Photo by Julian Wan on Unsplash

Knowing our limitations, but also our strengths, we can discover a way to carefully and safely resume daily life while adapting to the coronavirus pandemic.

References

1. Loeffelholz MJ, Tang YW. Laboratory diagnosis of emerging human coronavirus infections – the state of the art. Emerg Microbes Infect. 2020;9(1):747-756.
2. Lippi G, Simundic AM, Plebani M. Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). Clin Chem Lab Med. 2020.
3. Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020.
4. Guo L, Ren L, Yang S, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis. 2020.
5. Xiao DAT, Gao DC, Zhang DS. Profile of Specific Antibodies to SARS-CoV-2: The First Report. The Journal of infection. 2020.
6. Farnsworth CW, Anderson NW. SARS-CoV-2 Serology: Much Hype, Little Data. Clin Chem. 2020.
7. Mo H, Zeng G, Ren X, et al. Longitudinal profile of antibodies against SARS-coronavirus in SARS patients and their clinical significance. Respirology (Carlton, Vic). 2006;11(1):49-53.

Cass Nelson-Dooley, M.S.

Cass Nelson-Dooley, MS, is a researcher, author, educator, and laboratory consultant. She studied medicinal plants in the rain forests of Panama as a Fulbright Scholar and then launched a career in science and natural medicine. Early on, she studied ethnobotany, ethnopharmacology, and drug discovery at the University of Georgia and AptoTec, Inc. She joined innovators at Metametrix Clinical Laboratory as a medical education consultant helping clinicians use integrative and functional laboratory results in clinical practice. She owns Health First Consulting, LLC, a medical communications company with the mission to improve human health using the written word. Ms. Nelson-Dooley is an oral microbiome expert and author of Heal Your Oral Microbiome. She was a contributing author in Laboratory Evaluations for Integrative and Functional Medicine and Case Studies in Integrative and Functional Medicine. She has published case studies, book chapters, and journal articles about the oral microbiome, natural medicine, nutrition, laboratory testing, obesity, and osteoporosis.