As Minnesota, and other states, are having a wave, still too early to tell how significant, and as this is likely well past the two year mark for when the virus really began infecting humans, no matter what China says, might be a good time for one of those periodic big picture summaries of what we know about the epidemic, about our responses to the epidemic, and what the future may hold. Readers who want to see a somewhat dated presentation I gave about the epidemic can find it on YouTube, along with some other lifestreams, I think. It has held up pretty well. I know many of you may not agree with everything I say, but that’s okay. I just encourage you to form your thoughts from sound research and analysis.
I will start with some real basics that hopefully everyone agrees with. CV-19 is one of many coronaviruses. Four common ones circulate constantly and generally cause colds, although it is likely some cases of flu are actually due to coronavirus infection. We have all encountered and do encounter coronaviruses on a regular basis. Most people never hear of coronaviruses because they really aren’t very threatening to humans, although two other ones in the last 20 years caused a potential epidemic scare. There is some evidence that over a hundred years ago one of the four seasonal coronavirus arrived in humans and caused a serious epidemic. It was likely only a matter of time before another more lethal version jumped to humans. There is ongoing debate about the natural or unnatural origins of CV-19. Not sure it matters at this point, other than as a warning that we shouldn’t be messing with pathogens and we should be alert to pathogens transferring from animal hosts to humans.
Coronavirus are called that because they are surrounded by a corona of spikey-looking protrustions that they use to enter the host’s cells. Viruses have only one purpose; they exist solely to replicate and don’t really care how much damage they cause to the host by doing that. Respiratory viruses tend to be present in very large numbers and to mutate frequently. They are historically very hard to vaccinate against. Like other viruses, CV-19 enters human cells and hijacks the protein making machinery contained in the cell to make copies of itself, lots of copies of itself, as many copies as it possibly make. And those copies leave the cell and go find other cells to infect and so on and so on and so on. A human can harbor a lot of viruses and they can make you pretty sick.
CV-19 gets into cells through its receptor binding domain which seeks out a common protein receptor on human cells called ACE 2. That receptor is present on most cells and the virus can eventually infect just about every kind of cell if it stays in the body long enough. The virus is almost always inhaled through the mouth or nose although it is possible you could touch something with the virus on it and then touch your mouth or nose area and inhale the virus. If it gets past your upper respiratory tract into your lungs, that is when the risk of more serious disease begins.
Astoundingly, there is a lot we still don’t know the details of CV-19 transmission. It appears certain that it can spread in droplets and finer aerosols which are spewed out by one infected person and inhaled by another. I think the bulk of the evidence suggests that the aerosols can persist for a very extended time and can retain viable virus capable of infection during that extended time. This accounts for the failure of contact tracing to be of much use in suppression. The virus may also be able to survive on certain surfaces, like masks, for some time, but there is little evidence to support significant transmisison from surfaces or by other means than droplets and aerosols.
We also don’t really know how infectious the virus is. It may have a fair amount of infectiousness, but it also appears that for most people an infection is mild or even asymptomatic, which suggests low viral loads, and many people appear not to get infected even on substantial exposure. I am always amazed at the relatively low rates of household transmission found in studies. By this point most of us have stories, as I do, of knowing a family member or close relative who has been infected and who has not infected a spouse or children residing in the same home. I believe the truth is, as a recent German study found, that CV-19, including the dreaded Delta variant, is not exceptionally infectious.
It also appears that there is immense variability in susceptibility to infection among the population and variation in infectiousness. This may be due to innate and adaptive immune response variation, on which more later, but this variability leads to a clear superspreader phenomenon in which the bulk of CV-19 transmission appears to occur from a few individuals with very high viral loads. Most epidemic modeling was a dismal failure largely due to not including variable susceptiblility as a key factor. Transmission can occur from people who are without symptoms or who have not yet developed symptoms, but the research would indicate that these people are not responsible for substantial proportions of all transmission. Most people when infected are infectious for only a few days.
We have seen over the entire course of the epidemic an astounding bifurcation of serious disease by age. Most hospitalizations and the vast majority of deaths occur, and continue to occur even after substantial vaccination programs, among the elderly and even more narrowly among the frail elderly. The primary reason is fairly obvious; the immune systems of elderly persons are generally weaker. And this may be exacerbated by a lack of exposure to seasonal coronaviruses that is common in children and younger people. We also have through our obsession with extending life, no matter what, built up a large pool of persons who are vulnerable to any significant disease or pathogen or life shock.
Let us now imagine we are a virus particle entering the upper respiratory tract. My, what a lovely moist, warm environment and look at all those cells with such welcoming receptors for the receptor binding domain on my spike proteins. But wait, what are these proteins and cells coming after me and, oh, oh, oh no, please Mr. Bill, oh no don’t do that. (An old SNL reference which you have to look up if you have never seen these animations.) In a healthy human when a pathogen, or any foreign substance is encountered, the immune system is triggered and has a response, the speed and strength of which will determine whether serious illness ensues. It should also be noted that the immune system is prone to over-reaction, and serious illness is often worsened by an excessive immune response.
Our body has an astoundingly complex immune system with multiple components, some of which act as sentinels. Some of these sentinels engage in general pattern recognition of chemical sequences often associated with invading pathogens. Others, particularly if a version of the pathogen has been encountered previously, specifically recognize a re-exposure. It appears that prior exposures to coronavirus may result in an adaptive immune response to any coronavirus that aids in repelling the impending infection. Circulating in our body at any one time are a large number of “memory” immune cells capable of recognizing specific pathogens. So in comes a load of coronavirus virions. You might sneeze, you might cough, there may other gross or high-level responses as to any invading foreign substance. But most importantly, you may have memory cells right there in your upper respiratory tract, and/or general pattern recognition cells and they immediately signal for help.
One component of the immune system is B cells, which mature in the bone marrow. Some B cells produce antibodies, which are inverse chemical sequences that can latch on to parts of an invading pathogen, in the case of viruses, often the part which is needed for cell entry. People might have some circulating antibodies which are capable of neutralizing virus particles as they enter, and some of those antibodies may even be in the mucus linings, as well as blood. But more typically, the appropriate B cells need to be signaled to start producing more antibodies. As a side note, having a lot of circulating antibodies to every possible pathogen would be great, but the body is pretty efficient, and it can’t waste time and energy having a standing army to counter every threat, say, the Bahamas as well as China. It tends to focus on what it has perceived in the past as extremely threatening and rely on memory cells to deal with the rest. I think the fast lessening of circulating antibodies following vaccination is because in general the immune system doesn’t think coronaviruses are that big a deal, and partly because the vaccines we are using don’t mimic the entire virus well enough to prompt a broader, more durable response.
In any event, while most of us have encountered, even been infected with a coronavirus, we were all originally naive to this one and it is different enough to give the immune system some problems. Children have strong general immune systems and lots of recent coronavirus exposure and the combination likely allows them to keep CV-19 from getting much of a toehold, or lunghold in this case. Many adults, not quite so much. So our naive immune systems, never having seen anything quite like this, have to start from scratch in building adaptive immunity. First specialized immune cells get the chemical sequence of multiple parts of the virus. Then the B cells make antibodies that can latch on to and block the activity of those parts of the virus. This takes a little time, and depending on how much CV-19 has replicated, you may need lots of antibodies. But you have other help, especially T cells, which mature in the thymus, and which can outright disable and destroy virus particles. But T cells specific to CV-19 also take time to develop. Other immune components are signaled and help as well. With a little luck, your immune system gets the job done pretty quickly and you have the sniffles, maybe you feel like crap for a few days. If not, if the virus keeps replicating and replicating and the immune system runs out of steam or just goes bonkers and starts trying to nuke the virus by killing every cell in sight, you can get really sick and even die.
But if you were infected and survive, now you should have some pretty good adaptive immunity. Again, not likely a standing army, but a rapid reaction force that upon a re-exposure to CV-19 will likely quickly repel the invader. Not going to keep you from getting exposed, may not stop some replication from occurring, but generally will defeat CV-19 in short order. Vaccines work by exposing the naive immune system to parts of the virus, mimicking a true infection and prompting development of that adaptive immune response. The mRNA vaccines actually work a lot like the virus, they get into a cell and get the protein machinery to make spike protein, which is pushed out of the cells and the immune system does its magic. Unfortunately, and I worried about this from the start, as far as I know these vaccines only use spike protein and therefore don’t do a good job of prompting a response to the whole virus. I think natural infection is proving to be more effective because it does prompt antibody and T cell response to membrane, nucleocapsid and even other parts of the virus. Traditional, attentuated virus vaccines are in development which should perform better.
Respiratory viruses have been around forever and we periodically have epidemics from them, influenza being the most common example. And we should know by now that our ability to stop or control those epidemics is very limited. But as the Greeks noted, humans have hubris. We over-estimate how wonderful we are and we don’t learn diddly-squat from our mistakes. If anyone had any doubt about our ability to defeat a respiratory virus, this epidemic should end that foolish notion. How many hundreds of billions of dollars have we spent trying to do that. Dumb, dumb, dumb. And I have no doubt that we won’t have learned the right lessons the next time. Our limited ability to suppress respiratory viruses includes via vaccines, which we also seem to be learning again. The history of respiratory virus vaccines is bleak.
The governmental response to the epidemic has, in my opinion, generally been atrocious, with particularly pathetic communication to the public. The early responses were dominated by herd mentality of politicians who looked first to China and then around at each other’s actions. China? China? In any event, some genius decided that telling people to stay home, closing businesses, closing schools, just shutting people in, would interrupt transmission. Kind of funny since a lot of transmission occurs in the home. All I will say is that people can do all the dumb modeling studies they want, look at epidemic curves everywhere and explain how any of those tactics made any difference, especially in the long run.
Our public health experts, most of whom are employed by the government or academic medical centers, have distinguished themselves with their unrelenting poor advice, usually backed with no data or research. And I say this seriously, while some of these people may be bright and productive, you end up in government for a reason and people in both government and academia are highly risk-averse and not very good at logical analysis or sound decision-making. And as Exhibit A, I give you the responses they have crafted and are still crafting to this epidemic. Two years in, no evidence that any of it works–closing things down, testing everyone constantly and tracing contacts, masking, social distancing, plastic barriers every where–none of it has made a bit of difference. But they are still pushing the same insipid, inane measures, because by God, they might work this time. The politicians and the public health experts lack the basic common sense to say “we aren’t going to do anything until we have clear evidence that it will actually lessen spread”.
Worst of all has been the terror campaign and the lies and misinformation. People have been frightened into having an excessive fear of the virus, missing health care, missing social interactions. CV-19 is completely non-threatening to almost everyone. We can’t get accurate information from governments or the media, instead we get data and “research” which is designed solely to support the desired messages. Anyone who trys to inject a little truth and sense gets pilloried, banned from social media or even fired. What kind of screwed-up world and free society is this we live in?
We have been obsessed with reducing cases and deaths and ignored the damage caused by the steps we have taken as a result of that obsession. I have listed these harms repeatedly and they are beyond dispute at this point. And we did this ourselves, or rather our politicians did it and we generally stood by. Nothing from our Governor infuriates me more than his constant evasion of responsibility saying “the virus made me do it”. No it didn’t, you made a conscious decision, thinking only about making yourself look good by supposedly limiting spread, which didn’t actually happen, and your decisions were not balanced, did not consider the general public welfare and did cause substantial harm.
What would a better approach have been? It would have started with more respect for real data and science and more tailoring of mitigation measures to address the obvious bifurcation of serious disease. We should have focused on protection of the frail elderly, although realistically there was never a lot that could be done, and we forced absolute isolation on an already lonely group. We never should have closed schools or businesses. Mask mandates were and remain a delusion and a fetish. So yes, we should have accepted the inevitable and let people make their own decisions, with as good a data and advice as we could provide, about what activities they would engage in and what protective measures they would adopt. We would be in no different place than we are now, just faster and with less total pain.
CV-19 is taking us where we were always going to go. It is going to run through the population until enough of us have adaptive immunity, potentially aided by vaccines, to keep transmission and serious disease to a very low level. Florida may be there. Even then, it isn’t going away. Can anyone in their right mind actually believe we are going to suppress this virus? After all this time, after wave after wave, after massive numbers of breakthrough events? Not going to happen. We must attitudinally accept that.
What is going to happen, and I believe we are close in most parts of the world, is CV-19 will reach those low levels of transmission, probably be seasonal in nature, and it will cause some cases, hospitalizations and deaths. The serious illness will be mostly in the elderly, as it has been so far. We will likely have some ongoing exposure, which keeps our immune systems primed. And we will periodically see a new variant, just as occurs with flu, that has some greater lethality. We will survive all the virus can throw at us. Humanity will be fine. I am not sure we can survive the continued irrationality and deadliness of the government response.