INNOMINATA

In these Testing Times


Following the scramble to institute various forms of quarantine, most countries are now concentrating on COVID-19 testing. Here's what I know about the common methods of testing for viruses, kept as jargon-free as possible (I am not a qualified expert; this is an attempt to brush up on my pre-clinical knowledge).


Broadly speaking, we can test for a virus in two ways: see if the body has produced antibodies in response, or look for the virus itself. Before my brief and simplified rundown of virus testing, here's a brief and simplified rundown of the infection process.

The infection process #

When a virus infects a host, it enters cells and hijacks them to produce copies of itself. Viruses, along with other types of germs (and buses), have structures on their surface that mark them as foreign. What happens next depends on whether the body has been exposed to this particular virus in the past.


Suppose this is the first encounter with the virus. Patrolling immune cells spot the foreign invaders and call in other types of immune cells for help. They usually manage to get rid of the virus without much trouble but this can take some time, during which we may feel a bit crap. At the end of it, our immune system 'remembers' this episode and files away the virus in its criminal records.


On subsequent infections, the immune system mounts a much quicker response, clearing the virus before it gains a foothold. This is thanks to antibodies that were produced during the first infection. Antibodies target the virus specifically by binding to viral antigens - these antigens are special molecules on the surface that act like a fingerprint, and they are more unique to the particular virus than the generic structures in the previous paragraph. Think of a lock (antibody) that acommodates a key (antigen) cut to a particular shape. Antibodies deal massive crits and repel the virus more effectively than the generic immune cells in a first infection.

Detecting antibodies #

Two main types of antibodies are relevant to lab tests: IgM and IgG. IgM antibodies appear in reponse to a new infection and increase in number over a few weeks. They disappear after that and only provide temporary protection. IgG antibodies appear a bit later than IgM antibodies, but persist after the infection has resolved and confer immunity.


Antibody tests are also known as serological tests, as they are performed on blood samples. Positive IgM antibodies suggest a recent infection, whereas positive IgG antibodies indicate exposure to the infection in the past (including vaccination). However, an undetectable IgM level does not exclude a current infection; IgM takes time to increase in number, and may be undetectable in the early stages.


These tests can paint a fuller picture in retrospect, but on their own, they aren't very useful in diagnosing an ongoing infection. There's some debate about the use of antibody testing in the current pandemic.

Detecting the virus #

Viral culture #

Why not look for the virus itself? We can test for the presence of the virus in tissue samples such as saliva, sputum, and cerebrospinal fluid (pretty much any bodily fluid). Before the advent of fancy molecular techniques, the standard approach was to grow the virus in cell culture1 and then look at it under a microscope. The trouble is, many viruses either grow slowly in culture or not at all, and this method is only useful for a select number of viruses.

Antigen detection #

We can make use of specific antibody-antigen binding to detect antigens. Variations of this method rely on attaching a probe to each antibody before mixing the antibodies with tissue samples. If viral antigens are present in the sample, the probes stuck in the sample light up like a Christmas tree. Rapid antigen tests that don't require lab setups, while not the most reliable, are useful screening tools.

Nucleic acid detection #

If there was only test we could choose, it would have to be quantitative real-time polymerase chain reaction, or qPCR for short2. This method lets us identify the culprit directly, based on its genetic makeup. Using enzymes that work on DNA, qPCR allows us to make millions to billions of copies of small fragments of viral genetic material, like a money printer going 'brrr'3. Under proper lab conditions, qPCR is highly accurate, and even tiny amounts of virus can be picked up. Best of all, each test takes less than an hour to run! No need to wait days for the virus to (maybe) grow in culture.

COVID-19 #

qPCR testing of swabbed samples is the cornerstone of mass testing at the moment. Newer tests based on detecting antibodies or antigens are being rolled out in places, but it will take a while to determine how reliable they are. In the meantime, stay safe and - especially if your name is Ralphie - stay away from buses too.

Footnotes:

1 Fun fact: besides human cells, the most common cells used for culture are monkey kidney cells.

2 There is also reverse transcription PCR, which is commonly shortened to RT-PCR. The quantitative version of that is real-time RT-PCR. Quantitative reverse transcription PCR is RT-qPCR. Are medical acronyms confusing? You bet.

3 Sorry.

Day 2 of #100DaysToOffload

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