In order to slow and stop the COVID-19 pandemic, we need to be able to quickly and accurately determine who is currently infected and who has been infected with SARS-CoV-2. With these key pieces of information, we can identify hot spots for infection. We can also prioritize the allocation of resources to those who are most at risk. We can even loosen or tighten social restrictions in more effective ways.

There are 3 main types of COVID-19 tests available. These are:

  • Nucleic acid (molecular) tests
  • Antigen tests
  • Serological (antibody) tests

Each type of test has its own special features and uses. Indeed, as SARS-CoV-2 infection progresses, we need different diagnostic solutions. While PCR and antigen tests are useful for detecting SARS-CoV-2 during the initial stages of infection, serological tests are useful during the late stages and post infection. 

At Mammoth, we’re making CRISPR-based nucleic acid tests that are available at the point-of-need. We discuss all three kinds of tests in detail below.

Infographic describing the three kinds of COVID-19 tests and their uses. Nucleic acid tests detect viral RNA. Antigen tests detect viral proteins. Serological tests detect patient antibodies.

The 3 main types of COVID-19 tests: nucleic acid, antigen, and serological

We can break down the 3 types of COVID-19 tests according to their use. Then, we can divide them further according to the compounds they actually detect. Nucleic acid and antigen tests are used to diagnose active infection. They look for components of the SARS-CoV-2 virus itself. They look for these parts in nasal or oral swabs. Nucleic acid tests look for the SARS-CoV-2 RNA genome. Antigen tests look for proteins that make up the virus.

Serological tests (also called antibody tests) determine if a person was infected in the past. For these tests, healthcare workers take blood samples from patients. Then, they check whether these samples contain antibodies that bind to SARS-CoV-2. The presence of such antibodies indicates that the patient mounted an immune response to SARS-CoV-2 because they were infected in the past. This does not necessarily mean that the patient is immune to future SARS-CoV-2 infection. More research is needed to determine what immunity looks like.

Pros and Cons of COVID-19 tests

Like all assays, each type of COVID-19 test has its own pros and cons. All three are necessary for controlling the pandemic.

Nucleic acid tests

Nucleic acid tests usually make use of a targeted nucleic acid amplification technique such as the polymerase chain reaction. Such amplification techniques turn the small amount of viral genomic material in patient samples into large amounts of DNA. Researchers can use a variety of techniques to detect these large amounts of DNA.

Because of the targeted amplification step, nucleic tests are usually highly specific and very sensitive. They can be used to detect infection early and remain capable of detecting the SARS-CoV-2 genome weeks into infection. Yet, they can also be time consuming. Sometimes they also require bulky lab equipment.

Our CRISPR-based SARS-CoV-2 DETECTR is a nucleic acid test that overcomes the negatives of standard nucleic acid tests. It combines nucleic acid amplification with CRISPR-based detection. CRISPR-based detection both enhances specificity and amplifies signal further. As a result, less time is required for the whole test. In its current form, the test requires no bulky lab equipment. We aim to make it portable, disposable, and capable of producing results at the point-of-need. Thus, patients and healthcare workers will be able to use the test at decentralized locations and act on the test’s results quickly. Learn more here.

Antigen tests

Antigen tests use antibodies to detect protein components of the SARS-CoV-2 virus. These tests can be very rapid, but they’re often less sensitive and less specific than nucleic acid tests. Thus, a negative result from an antigen test is not a good indication that a patient is free of infection. For this reason, the WHO does not currently recommend using antigen tests for COVID-19 diagnostic purposes. Nonetheless, many are working on improving antigen tests. More research is needed, but antigen tests should be able to detect the SARS-CoV-2 virus around the time of symptom onset.

Serological (antibody) tests

Serological tests are rapid but have relatively low specificity and sometimes give false positives. Indeed, this issue is compound by the fact that SARS-CoV-2-infected individuals produce varying amounts and types of antibodies. Thus it’s not clear what the limit of detection for these tests should be. Serological tests generally detect infection a couple of weeks after symptom onset and beyond. This is because it takes some time for patients to develop an immune response.

Nonetheless, serological tests with known levels of specificity and sensitivity can be incredibly useful to epidemiologists. They can rapidly use these tests on large populations. With the resultant number of positive tests and the known specificity/sensitivity of the test, they can estimate how many people in a given population have been infected. Such information may be useful when officials decide whether or not to lift social restrictions. The US National Institutes of Health is currently conducting such a “serology study”.

Test test test

All three kinds of COVID-19 tests will be useful to slow and stop the COVID-19 pandemic. Combined use of nucleic acid and antigen tests can make us more confident in our diagnoses. They enable patients and healthcare workers to treat and isolate patients who are infected and who may develop serious disease now. Serological tests can help epidemiologists understand how many people have been infected and may make it easier to assess the effectiveness of COVID-19 treatments and vaccines

Mammoth and other organizations will continue improving these tests to make their administration and deployment easier. In particular, we believe it is critical to make point-of-need diagnostics that identify infection rapidly. With results from a point-of-need diagnostic, a patient can consult with a care-giver to determine what actions they can take in real time. Widely available point-of-need diagnostics will make it possible to control not only COVID-19 but many other devastating infectious diseases.