Testing

COVID TESTS: Kinds, Accuracy, Application, Interpretation

General guidelines

All available Covid tests have significant false negative rates. False negatives arise because the sample doesn’t have virus in it even though it is in your body. This means that a negative test result doesn’t guarantee you are not infected. If you have symptoms of Covid or a strong suspicion that you have been exposed it is important to test at least twice (and sometimes more) and continue to isolate until symptoms resolve or consultation with a medical authority indicates that your likelihood of Covid infection is small. Asymptomatic infection does not preclude transmission: people infected with Covid may not experience symptoms while still being infectious to others.

PCR tests

Polymerase Chain Reaction (PCR) tests, also called a nucleic acid amplification tests (NAAT), check for the presence of SARS-CoV-2 RNA sequences from even low levels of genetic material in a testing sample.

• Advantages:

1. High sensitivity — good diagnostic accuracy (though still 30% false negative rate, so if you test negative you may still be infected), can be used in the absence of other confirmatory tests
2. Low false positive rate: so if you test positive it means you are infected (testing again might give you a false negative, but doesn’t mean you aren’t infected)
3. Available generally at a point-of-care, and in home test kits that can be ordered online and sent to a lab for analysis

• Downsides:

1. 30% false negative rate (a negative result does not rule out infection)
2. Testing is relatively expensive (but test costs may be covered by insurance) and time-consuming: results may take up to several days (but some PCR tests return results in 15 minutes).
3. May continue to detect viral RNA long after resolution of infection (you may continue to test positive after you are no longer sick or infectious)

• Good practices:

1. Seek confirmatory tests if initial test result is negative (since false negative rate is non-zero)
2. Report symptoms to primary care physician
3. Practice quarantine if exposure or infection are suspected even in the absence of a positive test result
   1. While waiting for test results (with or without symptoms)
   2. Isolate if symptoms are present even if a test result is negative. Seek re-testing (via PCR and/or antigen tests)
   3. Protect others by wearing a mask if having to leave home for essentials
   4. Obtain HEPA filters to coean air and open windows to allow frequent air circulation
   5. Disinfect frequently used areas

Antigen tests

Antigen tests recognize one or more specific proteins that are part of the SARS-CoV-2 virus

• Advantages:

1. Antigen tests are highly specific so that if you test positive you almost surely have it.
2. Home test kits can be done easily and give results in a few minutes.
3. Low cost, which varies by country and product (ranging from $1 to $20 per test, and often sold as batches of 2 or more tests).

• Downsides

1. Antigen tests have overall lower sensitivity than PCR tests (they are about 50% false negative) so even more than the PCR test you may still be infected if you have a negative result.
2. A lot of virus is required to produce a positive result
3. Low viral load (especially soon after infection) may result in a false negative result even when a person is infected
4. Negative results of an antigen test should thus not be used to confirm absence of infection.
5. Asymptomatic infected individuals who have been vaccinated may falsely assume that they are unable to transmit the virus. This is incorrect. It is important for both those who have been vaccinated and those who have not to be mindful of the accuracy, appropriate use, and sensitivity of antigen tests.

• Good practices:

1. If exposure to SARS-CoV-2 is suspected an antigen test is negative, it’s wise to schedule a PCR test and to take a second antigen test a couple of days after the first negative result.
2. It is important to quarantine and limit social exposure until at least a second confirmatory negative result is obtained. In the presence of symptoms, stay isolated even with a negative test.
3. Interpretation of test results. If you are uncertain about antigen test results (faint second line): contact healthcare professionals to obtain guidance for interpretation (link); the appearance of two lines (however faint) should be interpreted as a positive result.

Antibody (serology) tests

Antibody (serology, Ab-RDT) tests look for Antibodies, which are proteins in blood made by our immune system as a result of infection or vaccination in order to fight the current or future infection.

• Advantages:

1. Antibody tests can help determine whether a person was infected at some time in the past even if there were no symptoms or positive test at that time.
2. Antibody tests are useful during the period of time that a person is recovering from an infection.
3. Antibody tests be used for research on population exposure as long as their limitations are recognized.

• Downsides

1. Antibody tests are not as helpful as PCR and antigen tests for identifying recent infections.
2. Antibody tests generally have a few percent false positive results, so they will rarely but importantly identify someone as having been infected when they were never infected.
3. Antibody tests should not be used for making clinical decisions unless other tests are not available.

• Good practices:

1. Antibody tests detect the body’s immune response to the virus in the form of antibodies. These tests are not accurate at the beginning of an infection but become quite accurate around 15−21 days post-infection. Antibody detection tests should not be used for determining active infections in clinical care or for contact-tracing purposes. Interpretation of results should be done by an expert and is dependent on several factors, including the timing of the disease, clinical morbidity, the epidemiology and prevalence within the setting, the type of test used, the validation method, and the reliability of the results.
2. It should be noted that the presence of antibodies that bind to SARS-CoV-2 does not guarantee that they are neutralizing antibodies or that they offer protective immunity. However, antibody testing may be useful for serosurveillance studies to support the investigation of an ongoing outbreak and for the retrospective assessment of the attack rate or size of an outbreak.
3. Serologic rapid point of care (POC) tests are popular because they yield fast results (about 15 min), can be done at the point of care, and are easy to use. These qualitative tests are generally implemented as lateral flow assays (LFA).  Using LFA antibody tests for COVID-19 gained traction due to the rapid turnaround time as decision-makers strive to quickly understand the extent of SARS-CoV-2 infections in their communities.
4. Public health organizations have recommended that serological tests be used only to detect antibodies to SARS-CoV-2 in order to identify people with past exposures and those recovered from COVID-19, rather than as the sole basis for diagnosis of COVID-19.