So, you want to ask good covid-19 questions? Start here.

I’ve been frustrated by the lack of presentation of science, while we are dealing with this pandemic. I don’t think any science is “rocket science” if it is taught clearly and people ask questions. We are all learners and great questions often come from those not steeped in a particular domain of knowledge because they are not biased towards well-worn paths. But science is also not uninformed opinion, so here’s my narrative today.

Viruses seem so small and we hear lots about antibodies, so they must be really big, right? What does having an antibody to covid-19 mean? Does having antibodies to covid mean I’m immune?

Antibodies (https://www.britannica.com/science/antibody) recognize an “epitope” — which is about the length of 6 amino acids (see below — this is 2nm, or ~1/15 the diameter of the viral particle). These can be adjacent epitopes, i.e. amino acids in a row in the protein, or amino acids that are close together because of folding.

There are many kinds of antibodies and antibodies that do different things because of where they bind to an antigen (or the actual binding site — the epitope). The gold standard, that reflects immunity, are called neutralizing antibodies. When they bind they inhibit infection. That would be the fastest way to eliminate the virus from your body. Other antibodies would bind and elimination of particles would take longer or maybe not happen, so you don’t have clear immunity.

Disclaimer, I am not an immunologist, so what I know about these is based on my background in biochemistry. Ask an immunologist about how the immune system builds up a reaction to an antigen or invasive organism.

What size are these things and does it matter? An antibody is about 10nm in size (https://en.wikipedia.org/wiki/Antibody) and the covid-19 particle is 70–90 nm in size, so let’s say, 10 antibodies lined up end to end.

Your fingernail is about 1 mm (millimeter), 1,000 micrometers equal 1 mm, and 1,000,000 nm are equal to 1 mm. So, there could be more than 100,000 viruses or viral particles lined up the thickness of your fingernail.

Size (and what the ab recognizes — what it binds to) matters, because the size of the ab to the virus does limit how many different antibodies can bind at once. There are some great questions here. Many of the answers require different types of expertise, but they are not far.

How should I imagine what the antibody “sees”? The spike protein on covid-19 is made up of two parts, S1 and S2. S1 has (and I didn’t look up the sequence, this is from size measurements) about 550 amino acids and S2 has about 250. These proteins are folded to make the spike and they also have big chains of sugar molecules on them -which can impact folding, so antibodies, that actually recognize shape, polarity*, and charge of the epitope (a part of the whole antigen, in this case the virus) can recognize many different parts of the spike (from the linear amino acid sequence to structures formed by folds). That’s what makes identification of “neutralizing antibodies” difficult. The proof of these antibodies is that it stops infection — so you need a good model for this since you don’t want to experiment at this level on humans if you don’t have to.

We have mathematical models for protein folding and for what might elicit a good antibody reaction, we have some idea what part of the spike protein might bind to the ACE2 protein on the outside of human cells — that allows the virus to enter and replicate — but all our models have some predictable error. We have to make assumptions and biology can do things we have trouble imagining. But, this works many times.

So, antibody tests. A test that distinguishes covid-19 antibodies from general antibodies to corona viruses (like the common cold) will tell you if you have been exposed to covid-19. You might or might not have immunity. A test that can identify neutralizing antibodies will tell you if you have immunity and allow us to determine how long (in the absence of covid-19 mutation) that immunity could last. As a scientist, although there are reports of the identification of neutralizing ab, I am certain it will take a much longer time to know this is factual. But we might soon learn how many people were exposed.

The thing is the tests have to be good (https://www.nytimes.com/2020/04/19/us/coronavirus-antibody-tests.html?searchResultPosition=1) . In this arena, we worry about false positives (saying you’ve been exposed when you haven’t) and false negatives (saying you haven’t been exposed when you have been). When science is done in a rush or there is too much to gain from discovery, we can make mistakes — intentional and unintentional. Scientist are humans. So, don’t get the first test. If the announcement comes with trumpets, great visuals, etc. — be wary.

I’m not practicing medicine here, just talking science. But I wrote something to a great, good friend this AM that made me think of pulling this information together, because we have to trust that non-scientists are asking these kinds of questions and that having more people asking informed questions makes us smarter.

Here’s what I wrote “The challenge to all of this (covid) is that we are learning more every day. But MDs have to treat based on what we knew yesterday. It takes a strong team just to deal with that rapid shift — and then to communicate it to a nation that is so scientifically illiterate** and divided is the greatest challenge.

*ask if you want to know more

**this is another great discussion point and I think we have inadvertently created some of this ourselves. It certainly can be increased if we choose to. You can start by thinking about these physical entities, closing your eyes, and playing with them in your imagination.