Testing in the Age of COVID
There is a rule in medicine - Don’t order a test unless you are going to do something with the result.
Every COVID testing site is booked solid but should it be? Most of us don’t understand what the tests measure, and even fewer of us think about what we would do with a result. Let’s start by talking about testing in general, then review how COVID tests work, and then finally discuss what should be explained to people before they take a test.
Why Test At All?
Testing should only be done to:
Set a comparison point
Test your max deadlift to know how much you should lift in a routine workout
Test blood pressure relative to normal ranges
See changes
Test your VO2 Max to see if you are improving
Test blood pressure to see if it’s improving
Make a Decision
Test your skill to see if you are safe to drive
Test blood sugar to decide if you need insulin or more sugar
Answer a question
Test the internal temperature to see if the chicken is undercooked
Swab a surface to see if it is the source of an infection
Before you take any test, you should be clear about the purpose of the test -- what are you going to do with the result? Are you trying to understand why you feel sick? Whether you can go out tomorrow? Or see if you are safe to re-enter society?
Because we forget to first think about the purpose of testing, most testing is wasteful and leads us to make incorrect decisions using tests that don’t tell us what we needed to know.
And even if we remember the purpose, we have to ask ourselves if the test actually tells us what we need to know. You can test your BMI every day. But if the thing you want to know is “am I at risk of a heart attack?” it may not give you the information you actually need.
COVID Diagnostic Testing - Antigen
There are two kinds of tests for diagnosing COVID-19 Antigen and PCR.
Antigen testing looks for the presence of particular antigens (proteins) specific to a virus in a fluid sample. The COVID virus tends to multiply in the respiratory system, so the best sampling sites are the nasopharynx (where the nose meets the throat) and deep throat saliva. The anterior nares may also be swabbed because it’s more comfortable, but it tends to have fewer virus particles to catch.
Sample collection sites
NP testing is the gold standard but is uncomfortable to get to and poking way back in a person’s nose often causes them to cough or sneeze. Dangerous for the lab tech. Some labs are moving to saliva testing, because it is safer for the lab tech, but it requires a patient to grunt-up saliva from deep in their throat. Over a number of studies, saliva testing has been as accurate as NP testing.
Antigen testing works by mixing the patient sample with something that binds uniquely to the antigen (kinda like an antibody) and seeing if anything binds. If there is binding, you get a positive result. Antigen testing can be sent to a big laboratory or done on a test-strip in a few minutes.
Antigen testing is great for telling someone if they have COVID at the time they are tested and because it’s looking for the antigen proteins, it is good at detecting if someone is actually infectious / a risk to others.
Unfortunately, the rapid antigen testing is very very hard to get. If you get the test results a day later, it’s useless. Especially if you had to leave your house and interact with people in order to get the test, or see anyone while waiting for the result.
COVID Diagnostic Testing - PCR
A PCR test, or polymerase chain reaction test, can detect a piece of DNA from a specific virus. Samples are collected in the same way as an antigen test. The sample is sent to a lab where it is mixed with reagents, called primers and probes.
The mixture is placed in a machine that briefly heats the mixture, allowing the reagent to bind with a specific piece of DNA. Then the machine cools the mixture which causes the bond to break, and replicate that piece of DNA. The process repeats over and over for up to 40 cycles. After each cycle, you increase the amount of DNA of interest in your sample.
A PCR test works by measuring the amount of DNA of interest (fluorescence) at the end of each cycle. Once the amount of DNA crosses a threshold, the machine stops and reports how many cycles it took to get to the threshold. If after 40 cycles, it doesn’t cross the threshold, the process stops.
Examples of PCR testing results
The results of PCR testing allow patients to be grouped into three genomic load cohorts: low (Ct ≥35), intermediate (25<Ct<35), and high (Ct≤ 25). A person’s Ct number should change as they get sicker and recover, allowing a doctor to see how they are progressing. PCR testing is good at detecting low levels of infection because of the forced replicating.
Unfortunately, the Ct value is almost never reported, and the result is simply Positive or Negative, taking away the most valuable piece of information - how sick are you?
COVID Antibody Testing
Antibody tests look for antibodies that are made by your immune system as it fights off COVID. The immune response and antibodies can take time to develop after you become infected, and often appear as you are getting better, so it is not a useful test of how infectious you are.
Every person who gets sick develops a different level of antibodies - typically correlated to how sick you felt. Most people will lose their antibodies over time after they are no longer needed.
Not having detectable antibodies does not, however, necessarily mean a person is or isn’t immune to COVID. The immune system may keep a deep memory of how to produce COVID antibodies in cells called “memory B cells”. We do not have a way of telling if someone has memory B cells against a specific disease.
A lack of antibodies could mean 1) you were never sick, 2) you lost your antibodies but do NOT have memory B cells of permanent immunity, or 3) you lost your antibodies and DO have immunity in the form of memory B cells. On the other hand, a positive antibody test could either mean 1) you are sick now 2) you are not sick and are protected for now, or 2) you are not sick and immune forever because you also have memory B cells.
So antibody testing is only useful:
To see if you can donate blood plasma with antibodies to help others
To see if a vaccine provoked a response
Should You Get a COVID Test?
I can think of a couple good uses of testing.
If a person comes in sick to a hospital, a rapid test would tell everyone what safety measures to treat them with and conserve PPE
If a person was COVID positive, PCR testing that reports the Ct number is useful to know how their disease is progressing, and how to treat them.
Rapid antigen testing would be good to know if you are infectious right now. It can answer things like “can I visit X right now?” “Can I go to school / see patients/ work today?”
If you were exposed to someone with COVID, and have been strictly quarantining since, and it has been more than 5 days, a negative test result should make you confident you do not have it on the day you were tested.
What’s not being explained properly is that if you don’t use COVID diagnostic testing in one of the ways above, you are not seeing changes, or able to use the information to make a decision, or answering a question. In my opinion, the testing is a waste of time and resources.
We should either be testing way more often with rapid antigen testing so that people can go out that day, or we should be testing way less with tests that take days to get results.
Go Big or Go Home
In a world where every American had 14 rapid tests, and we all agreed to strictly quarantine and test ourselves once a day every day, we could find every person with COVID and completely stop the spread. Sporadically using tests that give you results 72 hours later is useless and a waste of resources. It’s about as effective as sometimes using birth control.
Much like with lockdowns, testing only works if we go big enough to completely stop the spread. "Slowing” the spread and means we waste more resources for a longer period of time.
Next time you are thinking about getting tested ask yourself what the information actually tells you, and how you are going to use that information. If it doesn’t change anything, save yourself the effort.
