Things I've learned about Covid-19

I've fallen a bit out of the habit of blogging so I figured I'd do something fairly easy to start to get back in the habit.  Over the course of the pandemic I've been learning a lot about virology.  Most of this is, as far as I can tell, very basic stuff from the perspective of a virologist but it was surprising to me and might also be new to you who are reading this.

Viral Load

First of all, viral load is important.  I'd normally thought of people as either sick with a virus or not sick previously.  The easiest way to look at this is from the tools we use to detect viruses.  The way a PCR machine works is that you double the amount of viral RNA in a sample again and again and eventually you have enough virus to detect it by macroscopic means.  The number of times you have to double the amount of RNA before it becomes detectable is called the cyclic threshold or CT value.  For a sensitive PCR machine you can detect RNA down to a CT of 37 to 40.  And the highest viral load I've heard of for Covid-19 was someone with a CT of 7, roughly 4,000,000,000 times higher.

CT values from different machines and sampling methods don't line up perfectly; because the number of virus particles for a given CT varies a bit from machine to machine and we don't necessarily know the exact way they vary the people operating these machines aren't allowed to tell doctors what CT value they got.  Different swaps from the same person's throat on the same machine can also have different levels of virus.  However, because these values range over may more orders of magnitude than this inaccuracy they can still be useful, especially when aggregated between individuals for studying the virus.

It seems pretty clear that people with higher viral loads and lower CT values have more virus.  Intuitively it seems like someone with a hundred times more virus in their respiratory system would need one hundredth as much time on average to infect another person.  This hasn't been rigorously demonstrated, though.

Disease Progression

The big difference between SARS-CoV-2 and the original SARS that has turned this one into a pandemic is that a persons viral load actually tends to peak almost a day *before* they start exhibiting any obvious symptoms.  That was something I was skeptical of in early February when there were still conflicting reports but it seems quite well established at this point.  That's also why the average time for the number of Covid-19 infections to double can be smaller than the average time from infection to symptoms, another thing that confused me early on.

After symptom onset the viral load tends to keep decreasing over time even as the patients symptoms might continue to get worse.  Most people who end up in the hospital don't become very sick immediately but will have a period of moderate symptoms for 7 to 10 days before taking a turn for the worse and ending up needing extra oxygen or worse.  The immune system apparently, unable to actually defeat the remaining virus, just gets more and more aggressive and damages the lungs as a byproduct.  One big problem this causes is that drugs that cut down on viral replication don't do much by the time someone ends up in the hospital, by that point the number of viruses is already low and declining.  But giving intravenous drugs to everybody who might later become very sick has been too logistically challenging for us to try so far.

Non structural proteins

In any virus there are some genes that code for the proteins that later go into the virus.  In SARS-CoV-2 the most famous of these is the spike protein but there's also a couple in the envelope and one that holds the RNA.  Besides those there are also other genes directly involved in replication that work to assemble the virus and, in the case of coronaviruses, proofread the copying of the large genome.

But a virus needs more than that to cause an infection.  The body's first line of defense against disease is the skin and other barriers.  Without these you'd be dead in hours.  After that is the innate immune system that protects against general classes of diseases.  For instance, a cell infected with any virus will try to use interferon to protect the body.  So any virus that causes an infection has to have some strategy for dealing with inteferon.  In the case of SARS-CoV-2 it has a gene called Orf6 that protects it against interferon.

The body also has an adaptive immune system that evolves countermeasures to specific pathogens in the form of T cells and antibodies.  Covid-19 seems to somehow also attack the germinal centers where these cells are trained.  I don't understand the mechanism and I'm not sure anybody does but the sophistication of SARS-CoV-2's mechanisms for evading the immune system seem related to its large genome, with various genes interfering with the immune response in various ways.

I had previously had very little appreciation of the innate immune system and hand't realized that viruses tried to actively interfere with immune functions.

Enveloped virus means doesn't like drying out.

Earl on in the pandemic a lot of the information coming out was analyzing things like how long the virus could remain suspended in the air or how effective masks were in terms of the diameter of the virus, less than .1 microns.  However this doesn't really make sense.  Some viruses, like a norovirus, are have structures made entirely out of protein and are very resilient.  But viruses like coronaviruses have a lipid envelope as a critical part of their structure.  I guess there are advantages to this from the virus's point of view but it does mean that the virus is more delicate.  For one thing it means that soap can disrupt the viruses form but it also means that viruses of this sort generally can't remain infectious after drying out.

The smallest particle we have to worry about, as far as I can tell, are the aerosols caused by the action of the alveoli in our lungs.  These start out as 2 or 3 microns but shrink a bit as they travel, depending on things like humidity, and might end up just 1 micron wide by the time they fall out of the air.  This dependence on humidity be one of the factors that causes respiratory viruses to be seasonal.  But we probably don't have to worry about the .1 micron bare virus at all.

Lytic cycle virus

In the news there's recently been a scare about genetic material from SARS-CoV-2 being incorporated into the host cell's genome.  This probably was just a measurement error but it generally wouldn't matter because this is a Lytic virus.  That is, when it infects a cell that cell will build more and more of the virus.  But rather than being released as they are build the virus particles accumulate inside.  Eventually, when everything is ready, the host cell will burst and die releasing a flood of virus particles into the victim.  So it doesn't really matter if viral DNA ends up in a cell, that cell is doomed anyways.