The mass media floods us with contradictory messages. We must stay vigilant, wear masks, social distance, sacrifice our work, leisure and economic security, and prepare for the dreaded “second wave” of deadly infections caused by the SARS-CoV-2 virus. Yet at the same time it is socially acceptable to join tight masses of protesters in the streets to fight for the very just cause of eliminating racial discrimination and economic inequality. Nonetheless, that second wave is coming, they tell us. It is the real-life analog of a summer shark attack movie. And right on schedule the BBC has just announced that the policies of confinement saved “millions” of lives in Europe. Well, maybe. Who could ever prove that conclusion right or wrong? All we have to go on is the fact that this was the conclusion of Imperial College in London, and they could never be wrong about anything, could they?
In spite of the strange insistence of the mass media on always emphasizing the most pessimistic scenarios related to SARS-CoV-2—always cranking up the fear to eleven on the dial—many leading immunologists and virologists beg to differ. They insist that the pandemic has probably peaked and there will be no second wave. The pessimists, feeling very smart now that they have learned about antibody tests and such things, insist that at most only about ten percent of the population tests positive for antibodies, which is a number far too low to indicate that we are close to herd immunity.
Unfortunately, these overconfident new experts in immunology have set the terms of debate and made it very difficult for immunologists to explain that it just ain’t that simple. There is, in fact, a multi-lane highway to individual immunity and herd immunity. Mammalian immune systems have several immune system mechanisms that can defeat a new virus, most of which may not be accompanied by the production of antibodies. This was brilliantly explained recently in an interview with Creon Levit. He explains why these various layers of our immune system have probably raised herd immunity levels much higher than ten percent. Their effects are yet to be quantified, yet this theory of multiple pathways to immunity is the best explanation of why the pandemic has peaked and why we may be done with it. It is highly recommended for anyone who has felt tempted to lecture others about the apparent absurdity of the notion of herd immunity being achieved anytime soon.
A partial transcript follows. The entire interview lasts 1 hour 16 minutes. Originally broadcast on June 6, 2020
About interviewer, Ivor Cummins: “My Channel is devoted to bringing engineering problem-solving rigor and the scientific method to some of the more interesting issues in the world today. I have started with the Diabetes and Obesity Epidemic, but will move on to others as time permits.”
IVOR CUMINS (IC): We’ve got a must-watch episode for you today. We’ve got an all-round genius, a biophysics expert from Silicon Valley who has worked with some of the top immunologists in the field over the past many years. And he’s going to bring us through the immune system and how it pertains to this current corona virus issue and explain how it is not as people are viewing it at the moment, even the experts. So how the immune system works, how we become immune and what that means for this illusive concept, vilified concept even, of herd immunity…
[This diagram shows] what there is beyond the people who test positive for antibodies. Are there other people out there who fought off this Covid problem yet don’t show antibodies? That would be really important.
The unexposed population before SARS-CoV-2 hit was 100%, basically. They had not seen SARS-CoV-2. Then SARS-CoV-2 came along and it is argued… we won’t get into it… it could have been spreading a couple of months in the population before it received its signal to bloom, if you will, but we won’t get into that. But you could say that the only people, after the epidemic or pandemic has mostly passed, the only people who really got immune are the people who show antibodies in these new tests. And let’s say for a particular country, let’s say there’s seven or eight percent who are antibody positive. The orthodox opinion, very powerfully communicated, is that that country only has seven percent who have any kind of immunity. Therefore, they are nowhere near herd immunity, but from talking to you and from your excellent talk the other day, which I’ll also link to, there are other people who may have a considerable amount of de facto or effective immunity but not show antibodies. So I’ll just show them one by one and we can briefly comment on them before we get into the science. So what do you think about this: denatured or barriered type of people. Maybe you could describe that a little.
CREON LEVIT (CL): This is arguable, whether you’d call this immunity or not, but these are people who had gotten exposed to the virus and maybe even exposed to a load of virus who would have sickened other people, but because in these people, either through luck or their healthy metabolisms, the virus gets blocked through mucous membranes and other sorts of things and it never actually infects their cells. Now one might say that therefore they’re not even mounting an immune response and they could get challenged again, and perhaps infected. But some number of people who get exposed don’t get the disease, not so much because of a classic immune response but because it’s just blocked through their body membranes and other sort of nonspecific processes.
IC: So not immune per se but I think you mentioned earlier a good point that the people who have these effective mucous membranes, or whatever advantage they have, have got past it, and they’re not going to be a spreader. And if it comes along again, unless they get a huge viral load that’s much bigger or they become sick in some manner and their membranes become damaged or whatever, they’re generally going to be people over the two months of the pandemic who are kind of de facto herd immunity contributors because they’re not really developing the problem.
CL: I think we might say they are likely to be less susceptible certainly than the population that is easily infected. This is probably also a thing that gets worse as you get older, so it’s all mixed in with that.
IC: Again, I just mentioned we’re not quantifying these little segments. We’re saying that they exist in some manner and they need to be discussed. So the second [category] is “cleared by the innate immune system,” so maybe a brief chat on that.
CL: So we’re going to get into more details on this later in the talk, and then I have this much more detailed talk available elsewhere to talk about this, and then of course if you dive into immunology books, you’ll learn huge amounts about this, but the innate immune system means if you clear it using your innate immune system, certain aspects of your immune system, certain antibodies and certain other signaling processes can prevent or clear a viral infection even though you’ve never been exposed to that particular virus before. Even though you have no immunological memory, you have generic mechanisms in your body—most organisms do, certainly all mammals and even plants and bacteria have immune systems, and to some extent, especially in more primitive organisms, the only immune system they have is a generic system that targets generally all bacteria or generally all viruses. And so this is not a thing where you’d have specific antibodies to a specific virus, but you have signaling where virally infected cells do certain things and then the immune system, that innate immune system, starts setting nearby cells into sort of antiviral modes and stuff like this. And again, this is a type of immunity which we won’t discuss in that much detail, but some people manage to fight off infections, presumably, using their innate immune system without necessarily getting sick and generating an adaptive or acquired immune response, which is what we’ll get into next.
IC: So these guys, like these [pointing to the chart], but even more so because they really did have an immune battle, will go on to be de facto herd immunity contributors to society, but they won’t show antibodies. And just to explain to people the red X [on the chart] means you’re not going to see an antibody positive test for either of these or the ones we’re going to talk about now.
CL: I would say they may not show antibodies and they don’t necessarily have to show antibodies for these barriers and innate systems to actually work.
IC: Exactly. We can’t quantify the segment, but there’s a segment who successfully fight it off with innate [response] who will generally not show antibodies and maybe there are other people who have an innate response and also get to the antibody stage, but, yes, but we’re just talking about the segments that don’t show antibodies, yet to be quantified.
IC: Then the T-cells prior-adapted: again, briefly, because I know you’re going to get into this in detail. Fascinating stuff.
CL: One of the main routes, arguably, the main route for adaptive immunity is the mammalian immune system that has particular characteristics that are advanced and have evolved to target particular viruses or families of viruses. This is all centered around T-cells. T-cells are very complicated business. There are many kinds of T-cells, but basically if you get exposed to a new virus and you get infected, you can mount a T-cell response that targets that particular virus and that targets cells that are infected by that particular virus. However, you can also have previous infections from previous viruses that may have been similar enough to the virus that you’re currently infected with. So you have immunological memory. We’ve all heard about this. Once you get immune to something, you might stay immune for years, or for your whole life. You can have immunological memory that you get from viruses that are not identical to the current virus but are similar. So, for instance, there’s a question about people who were infected with Sars1. Do they have some immunity to Sars2? There are people who were infected with other corona viruses, like certain common colds. Do they have any immunity Sars2? And this is a new thing. Papers are coming out about this, but again you might have such prior immunity from previous similar but not identical viruses, and your T-cell system may act—potentially—to clear your body of the infection without generating a host of antibodies, particularly perhaps without generating antibodies that the SARS-CoV-2 antibody test tests for. The SARS-CoV-2 antibody test does not test for all possible antibodies against SARS-CoV-2. It only tests for a small fraction of the possible antibodies against SARS-CoV-2. Particularly, it tests for antibodies against SARS-CoV-2 that people who’ve been known to be infected with it have. But if you were never infected with SARS-CoV-2 but were infected with Sars1 or something else, you might have antibodies and T-cells that can fight off SARS-CoV-2, even though they’re not being tested for. This is all possible, and there’s new evidence coming showing it may be happening. So that’s why we draw the X here. We don’t know how big this wedge is. It may be very small or it may be quite big. We don’t know yet.
IC: That caveat, or a disclaimer, has to be said, for sure, but I think at the end [of the interview], after we go through the really juicy science, people who stick with us to the end will hear us talk about those papers when we revisit this pie chart. So that’s going to be interesting. So the next one is T or even B-cells, newly adapted.
CL: If you have never seen the virus before and you mount an immune response, that starts with T-cells and MHC, and things that we will go into shortly. You can clear the infection from your body by using a variety of different mechanisms. Your adaptive immune system invokes a host of different mechanisms in parallel to deal with viral infections, and it is not necessarily the case that it is going to activate a system that produces the antibodies that the antibody test tests for it. It activates a number of systems and your infection may get cleared, in principle, by one of the T-cell-mediated pathways like cytotoxic T-cells that aren’t tested for by the antibody test. So you might have people who are clearing the infection even though they are mounting a wholly fresh immune response to the infection but nevertheless test negative—but they’re immune.
IC: They are, de facto, contributing to herd immunity in the society but without triggering the test which is what we are talking about here. And then there’s the classic engineering false negative, and I think here you meant just people who have a very low level of antibodies below the threshold, or just the test kit doesn’t work. You are going to miss a bunch of people at some level.
CL: And to be honest, we don’t know. Not only do we not know the size of these wedges but we don’t know how many of these wedges are X versus just partial X. But these are all possibilities. These are all different classes of immune responses that might possibly not trigger an antibody-positive result.
IC: It’s a concept based in science but not quantified, and that’s fair enough. I think it’s really going to bring people the nuance around this. It’s declared with certainty, like let’s say in Ireland, that there’s only 2% of the people who have become immune. Even though the virus has run through society, it’s hit saturation death rates of 0.06 percent, and it’s on the sharp decline, it’s maintained that only two percent of people were exposed. So [the purpose here is] more to bring this up, to say hold on, there’s a lot more richness in this technology going on beyond that positive test. So that’s probably a fair way to summarize. Do you think so?
CL: Yes, and I think we need to be a little bit humble here. We really don’t know how much of this is going on, but new evidence has come to light over the last few days, particularly that something’s going on with these with these other wedges. There are strong hints that people who’ve been infected with other coronaviruses have some immunity to SARS-CoV-2.
IC: [I was reading the paper you sent me last night that said] that, if I can recall correctly, people who were known to be infected with SARS-CoV-2 were tested repeatedly with the antibody test, and six out of ten showed no antibodies. So again it’s a small number. It was only published a day or two ago, but it’ll illustrate to people that there is already data coming out. These wedges are all known, and they could be very significant.
Note: The participants in the interview used various terms for the virus SARS-CoV-2. For the sake of clarity, these were changed in the transcript to the single term which is the correct name of the virus.
Closing comment: Creon Levit informs us that a significant number of people, yet to be quantified, has immunity to the present corona virus because of their exposure to previous corona viruses. Therefore, we must ask what we think we are doing for the younger generation by trying to shelter them this year from exposure to SARS-Cov-2, a virus that is extremely unlikely to make them seriously ill. When the next corona virus comes along, they won’t have the immunological memory of exposure to this corona virus. Protective measures are often misguided and have unforeseen consequences.