Apiery Posted December 13, 2020 Share Posted December 13, 2020 Why are enveloped respiratory viruses generally seasonal? A few of the potential explanations: Outdoor temperature/humidity Indoor humidity More time spent indoors in winter Adaptation to the seasonality of the host's physiology Outdoor conditions make a lot of sense for wild hosts, but we live climate-controlled 93% indoor lives. Extra time spent indoors in winter can't matter all that much since that's where we spend almost all of our time anyway. Indoor air is significantly drier in the winter thanks to heating. Furthermore infectivity of droplets goes up very sharply as humidity is lowered below 40%. This is at least roughly where it would be expected to. So problem solved. We don't even need to look at that last option do we? Of course we do! No one ever said there was only one option. In fact there almost never is only one. Evolution is messy and it always hill climbs its way up along every dimension of freedom it has. DNA is just big long strings of base pairs, and any of them can be changed. So adapting to seasonal changes in the host must happen. The only questions are how much it matters and whether it contributes or detracts from seasonality. Turns out there are a thousand lines that suggest it favors seasonality and by a respectable amount too. Here's one that is unconfounded by any other reason: "In a double-blind placebo-controlled trial conducted in the Soviet Union during different seasons, nonimmune volunteers were given attenuated live influenza vaccine intranasally. Febrile reactions attributable to vaccine(calculated by subtracting the proportion of participants with reactions in the placebo group from the proportion in the vaccine group) were observed in 6.7% of 360 volunteers inoculated in Leningrad in January, compared with 0.8% of 197 inoculated in June (p = 0.003). Fourfold rises in antibody titer were seen in 31% to 40% in Krasnodar in January, depending on the vaccine strain, compared with 4.3% to 4.8% given the same strains in May and October (all p <0.001). Similar trends with less significant differences were seen in three other cities." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631809/ TLDR: Inoculating soviets in the summer avoided fevers and prevented the adaptive immune system from learning how to recognize the virus quite as well. If we are certain that everyone was infected then the cause must come from within the summertime host and not the wintertime one. Potential mechanisms for how aren't hard to come up with. So instead lets ask, 'Can we find reasons that explain why?' What is the evolutionary purpose of the seasonality of enveloped respiratory viruses? ERVs evolved outdoors and weather conditions result in an evolutionary preference about when to spread and when to simmer. Conditions below room temperature freeze their lipid envelope into a semisolid fatty shell. This is butter-clad armor; it helps them spread. So it is more cost-effective to proliferate in the winter. But what sort of coin pays this cost? Nonimmune hosts are a scarce resource. Hosts come in herds, herds are easy to propogate in until you run out of hosts. A frugal virus conserves hosts until fall when it has the best chance of spreading to new herds. The seasonal change in host immune tactics is the signal it takes advantage of. An upregulated adaptive immune system is easy to taunt into coughing. All it has to do is let the innate immune system keep its numbers in check during the spring and summer. The thinned numbers helps it avoid adaptive detection. This stretches out each host. Infection is asymptomatic, so no coughing and so less propagation. This stretches out each herd. The evolutionary game theoretic analysis has an equilibrium because the host's choice of tactics has a cost to it as well. Boosting innate immunity is like posting a guard at every corner and guards cost food. Stable play in the winter involves the host upregulating costly defenses to honestly signal to the virus whenever it is provoking the immune system too much. The virus prefers to not kill what could be a parent of future hosts. Virus and host come to a compromise. There are quite a few different costly signals that hosts can use. Fevers cost energy. Inflammation costs damage. All of these things are also inherently effective, they actually do things that kill viruses. It isn't just a request. But if a virus wanted you dead, you would be dead. They evolve so much faster. Fortunately the only way I can see this happening is if your species competes with a species they strongly prefer as hosts. Usually though before your kind is completely wiped out a strain of the virus will speciate. They then quickly adapt to play mostly nice and your species gains a symbiotic guardian whose purpose is to keep your immune system capable against its murderous parent. This is a charitable view of viruses as akin to militant warlords competing with one another for host species, ie territory. Like any military, they only have to exist because other militaries exist. What would a 'preferred host' look like? How about one that doesn't aggressively fight off viruses, yet never gets particularly sick from them, hibernates, lives in giant closely bunched herds, flies, lives everywhere, and is more diverse than any other mammal order besides their flightless cousins? Why, it's the goddamn bat's man! Ok yeah, my jokes aren't bat great... Anywho, bats seem like some kind of ecological appendix but for viruses and not bacteria. It's a bit of a mystery how their viruses remain so well-behaved. Bats can't signal to a virus when it is overstepping via fevers because they already get that hot every evening because flight is so demanding. Nocturnal frugivorous bats are completely disconnected from the vitamin D ecology. So no signals there either. Do they just have more effective innate immune responses always at the ready? This next paragraph is very speculative but intriguing. I wouldn't put too much stock in it. COVID-19 made the jump from bats to humans possibly stopping for a bit of pangolin on the way. Pangolins, with their body's perfectly covered in scales and a thriving on a diet of nothing but ants, make me wonder how their vitamin D system works. I wonder if anyone really knows. I also can't seem to quickly find any estimate of how much vitamin D is in a gram of ants. Anyways, if COVID-19 went from bats to pangolins and if pangolins are a bit idiosyncratic w.r.t. vitamin D then this could be expected to result in a virus which has not yet re-tuned itself to live once again in a vitamin D-typical host species. Add to that high levels of human deficiency and you have a recipe for a disease which might respond dramatically to improvement in D status. Let's look at our vitamin D system. Dietary D3, cholecalciferol, seems to immediately predominantly partition itself into our lipid fraction. Thus it is doubtful it has any activity itself. It seems to simply be a buffer storing and smoothing our supply. Calcitriol is thought of as *the* active form, but I think something important may have been overlooked. Calcitriol is indeed the form that activates the vitamin D receptor but I think that it's precursor, calcifediol, may deserve similar recognition. Calcifediol is an inhibitor of VDR. I don't know if it is potent enough to matter but let's assume that it plausibly might be. There are half-lives associated to each of the 3 reservoirs of D and they are nicely spaced out. This suggests to me that there may be two signals. That's when I found out that calcifediol was an inhibitor. The fluctuation of calcitriol level will trail that of calcifediol because it is made from it. The combination of a time-delayed agonist signal and a more immediate inhibitor signal allows our chemistry to derive what is effectively a time-delta of the agonist signal. That is, VDR expression can react to not only the level of calcitriol but also the rate of change of that level. There is a problem though. The signal would be very weak given how closely -triol tracks -diol. Fortunately this is no issue for the ever clever evolution. The VDR actually significantly upregulates its own expression! This is an unusual feature; we expect biochemistry to predominantly favor stability. However such homeostasis would dampen the time-delta signal. Because of this self-upregulation the impact of both agonist and inhibitor are amplified. Is this something that is known to happen elsewhere? About 2 hours ago I realized that this means that you can simulate the signal that winter is becoming spring by administration of the inhibitor. A sudden dose of calcifediol in someone deficient looks like if you went instantly from a winter pallor to a summer sunburn. The significance of this is that if enveloped respiratory viruses are generally attuned to the vitamin D host seasonal status responses then this wouldn't merely just signal to the virus that winter has ended, it would scream it. This is a signal that is impossible for our natural physiology to make. There was a pilot RCT that did exactly this for COVID-19 pre-ICU patients some months ago. Its results were literally too good to be believed. I am writing this today because the medical community has been largely dismissive to the very possibility that the study observed what it claims. No one wants to talk about it. I think it just doesn't smell right to many an epistemic nose. I personally can't see any reasonable way for the study to be anything except either fraud or truth or a 7.7*10^-7 ≈ one-in-a-million fluke or something I personally can't see. Please excuse the tautology. Lately it feels like vitamin D has been vitamin disappointment. Add to that the idea of effectively completely treating an infectious disease with a vitamin. It's no wonder people are so skeptical, and rightly so. Medicine and nutrition are incredibly epistemically noisy fields. However I sincerely believe that diligence is due here. In this case its not just the same old parable of the society who called 'wolf!' one million times too many. This time the cry happens to be a surprisingly detailed description of a wolf. If you agree with me that it should be talked about even if only to make a cogent counter-case, I encourage you to please share this with a peer or maybe a superior and spark a discussion. We are in bystander effect territory. Those who feel the same as I have been trying to figure out how to call the police but there doesn't seem to be anyone who will listen. If you know the right number for me to dial please tell me. I really want to be able to go back to my mathematics. Thank you for your time. Resources: A summary of evidence both pro and con An in depth analysis of the pilot RCT An excellent philosophical treatment of the decision theory Link to comment Share on other sites More sharing options...
CharonY Posted December 14, 2020 Share Posted December 14, 2020 ! Moderator Note Only one thread per topic, please. Link to comment Share on other sites More sharing options...
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