COVID-19 tests explained for dummies

Watchouts / Disclaimer

• I'm just an engineer trying to share publicly available information and put it in simple terms that anyone can understand.
• DO NOT MAKE ANY DECISIONS BASED ON THE INFORMATION IN THIS ARTICLE.
• IF YOU THINK YOU'VE BEEN EXPOSED TO SARS-COV-19 OR HAVE BEEN IN CONTACT WITH SOMEONE DIAGNOSED WITH COVID-19, YOU SHOULD SELF-ISOLATE AND IMMEDIATELY CONTACT YOUR HEALTHCARE PROVIDER.

Common COVID-19 tests

There is a lot of misinformation around COVID-19, the pandemic, testing, immunity, and so on. My goal here is for you to understand what COVID-19 testing is all about and why we can trust or not some of these tests.

In terms of testing, there are three main paths that allow us to infer that the SARS-CoV-19 (name of the virus) is in our bodies:

1. RT-PCR testing: detects the presence of the virus's genetic material.
   
2. Antigen testing: to detect the presence of the virus's antigens (e.g. the little spikes surrounding the virus).
   
3. Antibody testing: to detect the presence of specific antibodies produced by our body to combat (inactivate) the virus.
   

Executive summary: what you need to know

• If you get a positive PCR or Antigen test: you can be very convinced that you have the virus, even if you don't have any symptoms ( >99%). [1]
  
• if you get a negative PCR result: it's probable that you currently don't have the virus (80% chance). [2] [3]
  
• if you get a negative Antigen result: in general, you cannot conclude anything, you can either have or not the virus.
  
• Antibody tests will not tell you if you have the virus or not: You'd likely waste your money unless your government/health organization/physician has ordered you to take this test.
  
• Finally, you always need to watch out.

Why?

Everything can be summarized in terms of two important statistical concepts: sensitivity and specificity, which are key to understand and compare all the different test types we've discussed so far.

Sensitivity

Sensitivity: just imagine for a second that you have the virus, and you know you are infected (say we placed a sample under an electron microscope and saw the spiky virus floating around), however, you still want to get PCR tested, just to double check.

The sensitivity of a test tells you how good is the test at "sensing" that you have the virus, given that you have the virus.

Let's assume you received your test results and it says that it was not able to detect any evidence that you have the virus (but you and I already know that you indeed have the virus), you would then say to yourself "well, that's a pretty darn bad test".

This is known as a false negative.

In general, the less sensitive a test is, the more false negatives it'll throw.

SARS-CoV-2 coronavirus as seen under an electron microscope (colorized), by NIAD.

Sensitivity is determined and affected by several factors. Let's take for instance PCR tests: a sample collected from your nasopharynx is processed to later isolate its genetic material, and further processed to detect a particular gene corresponding to the coronavirus.

If done right, PCR tests can be highly sensitive (more than 95%), however, the sad truth is that in practice it can be as low as 80% [3] due to several factors, such as :

• How well the sample is collected, stored, processed, and analyzed by health-care professionals.
• The type of sample is used: saliva vs nasopharyngeal sample (the latter being more sensitive). [4]
• The time when the sample was taken after virus exposure. [5]
• Etc.

Similar problematic factors and the nature of antigen tests make their average sensitivity be as bad as 56.2%. [6]

In summary, getting a negative result from either a PCR or antigen test doesn't necessarily mean that you don't have the virus due to these test's variable and oftentimes low sensitivity.

Specificity

Most tests, whatever type they are, boast their high specificities. This means that whenever any of those tests throw a positive result, it's very unlikely that this result is wrong. In other words, the more specific a test the fewer false positives it'll throw.

If you think about it, it's rather intuitive to conclude that many tests, in general, are more specific than sensitive. Take for example the PCR tests again: as discussed before, several steps of the whole testing procedure might go wrong and, if so, the test will easily fail to throw a positive result when it should (this is, for a person that in fact has the virus)… this means that it's pretty easy for a test to lose sensitivity if things go wrong.

However, the chances of a PCR positive result being incorrect are pretty low. The reason for this is that this test tries to detect particular genetic sequences tight to SARS-CoV-2's ARN and getting a false positive result is remote.

The specificities of both PCR and Antigen tests are very high (>= 99%). [1]

GT-PCR is in general a better test due to its higher sensitivity and specificity compared with other tests.

Antibody tests

Antibody tests will not tell you much if context is left out of the equation. For instance, if you get either a positive or negative antibody result you cannot conclude that you have the virus or not.

These tests detect antibodies that bind to specific proteins (a.k.a. antigens) that surround SARS-CoV-2 virus, such as the ones shown in the image below. Antibody tests can detect the binding of antibodies present in our blood to one or more of the virus' antigens. [7]

Structure of a coronavirus by SPQR10

Our bodies produce several types of antibodies as well. However, two main antibodies are commonly detected by these tests:

• IgM: These are short-lived antibodies, which are produced first as an earlier response to an infection. SARS-CoV-2 antibodies remain detectable between 5 to 21 days after symptoms onset [8].
  
  
• IgG: These are normally produced shortly after IgM antibodies [8]. IgGs are detectable around day 14 after symptoms started. IgG levels in our blood will keep growing and plateau around day 28 to 35 since symptoms onset and remain in our bodies for months or even years (we don't know that yet). [8]

IgM and IgG production and seroconversion (i.e. when a test throws a positive result for either IgM or IgG) can vary quite a lot from person to person. Some people will seroconvert first for IgG, others for IgM, or even for both antibodies at the same time [9]. Some will no seroconvert at all. [9]

The table below shows why getting an IgM/IgM positive or negative result won't tell you whether you currently have SARS-CoV-2 in your body or not, yet still conveys other useful information:

These tests' results are particularly useful if complemented with your current state/symptomatology to get a better diagnosis. Nonetheless, and in general, these won't really tell you whether you currently have the virus or not.

Immunity

I'll just keep this section short and sweet:

• Little is known about long term immunity to SARS-CoV-19. [12]
• Some promising studies have shown that IgG antibodies may stay in our bodies for up to 7 months (or even more). [13]
• Immunity is NOT ONLY determined by antibody presence, other factors such as T and B cells might also determine long-term immunity. [14]

References

[1] https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html (accessed on November 21st, 2020)

[2] https://www.who.int/news-room/q-a-detail/coronavirus-disease-covid-19 (accessed on November 21st, 2020)

[3] https://www.cap.org/member-resources/articles/how-good-are-covid-19-sars-cov-2-diagnostic-pcr-tests (accessed on November 21st, 2020)

[4] https://www.idsociety.org/covid-19-real-time-learning-network/diagnostics/RT-pcr-testing/ (accessed on November 21st, 2020)

[5] Lauren M. Kucirka, Stephen A. Lauer,  et al. (2020). Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure. Annals of Internal Medicine. http://dx.doi.org/10.7326/M20-1495 

[6] Dinnes  J, Deeks  JJ, et al. (2020). Rapid, point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection. Cochrane Database of Systematic Reviews, Issue 8. Art. No.: CD013705. DOI: 10.1002/14651858.CD013705.

[7] Hu, B., Guo, H., Zhou, P. et al. (2020). Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. https://doi.org/10.1038/s41579-020-00459-7 

[8] Jacofsky, D., Jacofsky, E. M., & Jacofsky, M. (2020). Understanding Antibody Testing for COVID-19. The Journal of arthroplasty, 35(7S), S74–S81. https://doi.org/10.1016/j.arth.2020.04.055 

[9] Long, QX., Liu, BZ., Deng, HJ. et al. (2020). Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 26, 845–848. https://doi.org/10.1038/s41591-020-0897-1 

[10] Long, QX., Tang, XJ., Shi, QL. et al. (2020). Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 26, 1200–1204. https://doi.org/10.1038/s41591-020-0965-6 

[11] https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-covid-19-serology (accessed on November 21st, 2020)

[12] https://www.who.int/news-room/q-a-detail/herd-immunity-lockdowns-and-covid-19 (accessed on November 21st, 2020)

[13] Ripperger, T. J., Uhrlaub, J. L., et al. (2020). Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. Immunity, 53(5), 925–933.e4. https://doi.org/10.1016/j.immuni.2020.10.004 

[14] Rodda L, Jason N, Shehata L, et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. https://www.medrxiv.org/content/10.1101/2020.08.11.20171843v2