First of all, here's the full text in-case anyone isn't aware: https://www.nature.com/articles/s41586-020-2550-z_reference.pdf https://www.nature.com/articles/

First of all, here's the full text in-case anyone isn't aware: https://www.nature.com/articles/s41586-020-2550-z_reference.pdf https://www.nature.com/articles/s41586-020-2550-z_reference.... Before the actual paper, some review. REVIEW SECTION 1 Coronavirus is a family of viruses, viruses being basically pieces of genetic material that swim around, inject their DNA into other cells, which makes the cells produce more copies of themselves until thousands of baby viruses explode out of the cell, killing it and moving on to the next cell. COVID-19 is the condition that results from infection with SARS-CoV-2, which is a novel coronavirus that almost certainly emerged sometime in 2019. Think HIV/AIDS: HIV is the virus, AIDS is the disease, same with SARS-2 vs COVID-19. SARS-CoV-2 while technically novel, is incredibly close related to what we now call SARS-CoV-1, which we used to just call "SARS". SARS-1 was incredibly deadly, but the pandemic fizzled out, presumably because it is quite deadly/quite symptomatic and AFAIK there isn't pre-symptomatic transmission. SARS-CoV-2 structurally is very similar, sharing the same characteristic spike protein, and targetting the same ACE2 receptor which is expressed differentially in different tissue types. But SARS-CoV-2 is like a refined version of SARS-1, it "learned" from SARS-1's mistakes. So, it appears to be adapted to spread quite well, possibly because of cool things it does with interferon-mediated early course immunosuppression, which lets it spread for a few days before you show symptoms. It's also much less deadly than SARS-1. Now, to craft the "optimal" pandemic virus, you want something that spreads easily, has a long incubation time, and isn't too deadly (otherwise it fizzles out by killing its hosts before they spread sufficiently). So in that sense, SARS-2 is perfectly crafted to kill a bunch of people. But please don't fall into fear-mongering, it doesn't kill nearly as many people as most have been led to believe. In my opinion it's really quite a mild virus overall, but some people can have severe COVID-19 which presents very similarly to a more run-of-the-mill SARS-1 infection (remember the original SARS is very deadly, so run-of-the-mill != no-big-deal). REVIEW SECTION 2 We've talked about SARS-1 and SARS-2, but let me briefly butcher the immune system (I can already hear the immunologists stampeding towards me in the distance). Your immune system's job is to distinguish self from non-self, (or more accurately, "non-self that is actually a threat" since you can have bacteria/etc that are not pathogenic/pathological). When it identifies a target, it has a lot of cool ways to kill it, but the specifics of neutrophils and antibodies, etc are out of scope. For now, take it as given that your immune system can detect and kill pathogens. Once it has fought off an infection, you will likely have antibodies, which are little heat-seeker-missiles that are primed to detect and neutralize the pathogen in question. (Note there's also T-Cell immunity which operates perhaps orthogonally to antibody immunity. This paper talks about T-Cell immunity). Assuming you produced antibodies, eventually your active circulating antibodies will fade. This takes several weeks-a few months for SARS-1, and seems to hold for SARS-2, although I believe antibody prevalence is correlated with disease severity. So eventually you have no more circulating antibodies. Contrary to what doomers will tell you, that's not a bad thing, it's inefficient to perpetually maintain antibodies. So instead your body maintains a living library of the pathogens it has previously encountered. I'd encourage anyone to read about https://en.wikipedia.org/wiki/Immunological_memory https://en.wikipedia.org/wiki/Immunological_memory. I'll summarize briefly. (1) After infection, even when antibodies fade, you still have circulating Memory B Cells which persist across decades, waiting for exposure to the previously-fought-off pathogen at which they ramp up antibody production, leading to a faster, more strong response that results in lower peak viral load, presumably lower transmissibility/symptoms/etc. So, eventually it's possible to get reinfected as far as antibody immunity is concerned, but it takes quite awhile and when it does happen it's not nearly as bad. (2) There's also memory T Cells, which are similar except instead of relying on antibodies, they work with T cells, with basically directly kill pathogens rather than indirectly produce the antibodies with neutralize the pathogen. Okay, now it's time for THE ACTUAL PAPER The first finding is not surprising at all to anyone who has been reading research, but probably surprising to everyone else (read: almost everybody): if you've been previously exposed to SARS-1, you have memory T cells which persist long-term and will happily attack SARS-2. Remember when I said SARS-CoV-2 was a novel virus? Well, it was, but it was also incredibly similar to SARS-CoV-1. So, technically it's novel but in real terms it's only a little bit novel, so previous SARS-1 infection is protective. Well, that's cool, but most of us have never been exposed to SARS-1. But many of us have been exposed to one of the handful of other human coronaviruses that we know about. The somewhat shocking (maybe not shocking to those who have been reading about immunology for years) revelation in this paper is this: > Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). In other words, people never exposed to either of the two SARS viruses showed immune activation against SARS-2, meaning that they are either completely or partially immune to SARS-2. Why? Because they've almost certainly been exposed to some of the other human coronaviruses, which basically cause common colds. (Side note: For almost everybody SARS-2 is not any different from the common cold. It's quite rare to have severe SARS-2, but those that do get it experience very bad effects, since their immune system is basically ravaging their entire body) --- So the TL;DR: any model that has assumed that everyone can get infected is completely wrong and will massively overestimate the ultimate death of letting SARS-2 rip through the population. Many people will never be able to get SARS-2 because they've already fought off similar-enough human coronaviruses. (BTW, coronaviruses are very distinctive in structure so that is likely why our immune systems exhibit this cross-reactivity) Implications: (Warning: Strong opinion) As a result any cost/benefit tradeoffs of, say, lockdown, based off those models was off by a huge factor. The good news is, that even with the assumption that everyone was susceptible (capable of being infected), it was still really obvious to anyone with the capacity for rational thinking that containment/lockdown was a terrible idea, so these findings don't really change too much on that front, it just makes it even more overwhelmingly obvious that we collectively lost our shit and chopped off a limb in response to a papercut. So, instead of us (meaning, everywhere except Sweden) being super duper wrong, we now have good evidence that we were actually unimaginably, insanely wrong, to a degree that will be studied by subsequent scientists for decades as an example of where social contagion, groupthink and censorship led to one of the most damaging events in modern human history. Woot!