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Immunity and Re-Infection

For months now, people have been watching closely to see if it’s possible to get re-infected with the coronavirus. It’s taken a while for the signal-to-noise to get better, but by now there’s no doubt that the answer is yes, it’s possible. We’ve just had the first of these in the US, a man in Nevada who was infected twice six weeks apart, with the second round being worse than the first. And in the Netherlands, the first fatality from a reinfection has been reported. All this sounds immediately like bad news, but I’m going to break out the same advice I was handing out yesterday: don’t panic.

Why not? Because from everything we can see, re-infection is a very rare event. The confirmed examples worldwide could possibly be counted on your fingers (depending on whose count you believe) out of at least 38 million total cases. Looking at the Netherlands case, this was an 89-year-old patient with Waldenström’s macroglobulinemia, a type of leukemia that affects two different varieties of B-cells. She was being treated with chemotherapy to impair. B-cell production, and was thus immune compromised, and the second infection occurred two days after her latest round of treatment. Below is an analysis of the sequences of the first virus and the second – if you’d like more information about what a figure like this means and how to read it, see posts here and here.

You’ll note that there are not very many changes, and that all but three of them are nucleotide changes that make no difference to the actual coronavirus proteins. Let’s take a similar look at the two round of virus in the case in Nevada:

In this case, the red marks at the bottom are noting the changes versus the reference coronavirus genome. Comparing the two, you can see that these two strains had at least eight differences between them, but they’re both considered part of the “20C” clade of SARS-CoV-2, which is a largely North American family. There are several key things to take home from these sequences.

First off, in each of these cases, the unfortunate patients involved were infected by different variants of the coronavirus than they had the first time around. That’s pretty much what you have to show to be sure that it’s a real re-infection – otherwise you’d always wonder if the virus had just never really been cleared the first time. The first-round versus the second-round sequences show some real differences – not gigantic ones, but real. Second, these two second-round viruses were different from each other as well, so it’s not like some particular new supervirus is stomping around re-infecting people around the world. Third, in neither of these reports was it the widely publicized D614G strain coming back around the second time. That mutation really doesn’t figure into either of these cases at all, so watch out for anyone who’s mixing those stories together.

Fourth – and here’s where we start digging into some details – note that the mutations in both of these new re-infection cases have nothing to do with the Spike protein. There’s no change in the Spike in the Nevada sequences (they both had D614G), and the changes in the Netherlands sequences are conserved ones that don’t lead to changes in the protein in that region. Antibodies don’t care about genetic sequences; they respond to the eventual proteins that are displayed, and from what I can see, the Spike proteins of all of these strains are identical.

That’s important for several reasons. For one, the vaccines under development are all raising antibodies and T-cells to the Spike region. That was identified early on as the most promising antigen, building on the work during the SARS and MERS outbreaks. Note also this new paper, a thorough look at the various antibody fractions in patients who have recovered from coronavirus infection. The authors find that Spike-targeting neutralizing antibodies persist out to the limits of their study (five to seven months) while antibodies to the nucleocapsid region (N), which are also raised in most people by infection, disappear more quickly.

This leads to a hypothesis: perhaps in these two cases of re-infection, the patients either did not raise a very robust immune response the first time, and/or raised antibodies more to other antigen proteins compared to the Spike protein. That would account for the second variant being able to slip in under the immunological radar: the antibodies these people used to fight it back the first time were directed towards protein regions that had altered enough to make their recognition less effective.

What about the other confirmed re-infection cases? In the Hong Kong case, there were in fact mutations in the Spike protein, including the D614G, which led some people to wonder if such Spike changes were going to be a general phenomenon and lead to more re-infections. But these two new cases show that it doesn’t have to be that way. Note also that in that case, the first-infecting variant had 58 amino acids missing out at one end (a stop codon mutation in the ORF8 region), which is rather different as well. In the Belgian case, there was one amino acid change in ORF1a in the second variant, three in the Spike (including the D614G), and one in the N protein. The other mutations in the Spike, though, did not match up with the ones in the Hong Kong second variant. And in the Ecuador case, there were nine amino acid changes, but the only one in the Spike region was the D614G.

This is the time to note that a good amount of work has been done on the possible changes in infectivity, etc., of different coronavirus Spike mutants. And we’re not seeing a trend for viral evolution in directions that could increase re-infection or evade the antibodies that are raised by the existing vaccine candidates. The Nevada case, for example, showed the second variant actually had four amino acids that were back to the original Wuhan strain, rather that being something further and further out on the mutational limb. I’ve been looking through the re-infection papers and comparing the mutations seen with that link earlier in the paragraph, and so far anyway I’m not seeing a correlation between the second-round infections and the Spike changes that were flagged for changes in infectivity or antibody susceptibility. (And even some of those possible antibody-resistant mutants identified in that paper above turned out to be equally susceptible to the antibodies raised by the Pfizer vaccine when that team profiled them).

So the situation, for now, seems to be that yes, re-infection is possible. But it’s also quite rare. There are surely cases that we’ve missed, but it’s clearly not something that is happening much. We’re dealing with the fact that the human immune response is hugely variable from person to person – that’s one of its key features. Different people are going to raise different levels of different populations of different antibodies to a coronavirus infection, and that’s a big reason why the clinical course of disease is so variable. Even in these documented reinfection cases, we don’t know the details about what their first immune responses were like (there was no reason to profile these people in such detail the first time!)

Moving beyond that, I would suspect that vaccination, which raises neutralizing antibodies to the Spike protein, will provide a population that is even less susceptible to re-infection than we have in the wild-type-recovered population now, given that three of the five cases we have details of did not have significant changes in the Spike region at all. Now, we don’t know how long vaccine protection will last, or how variable it will be in a broad population – we’re out there getting those data now – but from what we’re seeing, I think the prospects are good. No panic necessary for now.

156 comments on “Immunity and Re-Infection”

  1. Matthew says:

    It’s not very rare, it’s just masked by other factors i.e. initial infection, etc.

    1. Ty says:

      Yes it’s very rare given the mIllinois infected you numpty.

      1. Fraud Guy says:

        And the next complaint will be that the patients were not taking hydroxychloroquine with zinc to boost their immune response…

    2. Mark Bahner says:

      “It’s not very rare, it’s just masked by other factors i.e. initial infection, etc.”

      There have been 38 million cases worldwide so far. Of those 38 million people identified, how many do you think we re-infections? Of those 38 million so far who were *not* re-infections, how many we get re-infected in, say, the next year or two?

    3. Semichemist says:

      …he says, hypothetically, with nary a shred of evidence

      1. theasdgamer says:

        There needs to be virus cultures with fewer PCR cycles as the standard.

  2. Philip says:

    I think vaccine protection durability is a huge question that will not be answered until after millions have received the vaccine. I don’t know of a way to answer the question without taking longer then we are willing. I doubt we even have six months of data before a massive number of jabs start.

    1. Deanna says:

      I agree. I have yet to hear of any protocol established to test immunity in the vaccinated.

  3. Gary Cornell says:

    If one imagines that immunity to this corona virus follows a normal distribution (bell curve) with a mean of say 9 months and say a standard deviation of 1 month then, while reinfections are rare now (say five standard deviations from the norm i.e. roughly 1 in 1.75 million) we should begin to start seeing more and more cases soon, no?

    1. Patrick says:

      But that’s not how immunity works? Immunity duration isn’t a normal distribution centered on some point in time. It depends on a lot of different factors, but I’m pretty sure it doesn’t look anything like a time linked normal distribution.

      For many diseases, it’s life long. For some, it barely happens at all (often due to high mutability of the disease). The small number of SARS patients we’ve examined seem to still have antibodies or other immune memory of SARS over a decade later.

      I’m pretty sure there’s no reason at all to think it works the way you’re suggesting.

      1. TabeaK says:

        You will also have a “boosting” effect upon re-exposure to the pathogen in question. Akin to the second or even third shot use for some vaccines to increase responses and titers. With SARS-COV-2 relative genetic stability I agree with Derek, no reason to worry about rare cases of re-infection causing problems. Our immune system is a very evolved marvel…and incredibly versatile on an individual level. Again, that doesn’t mean the rare individual cannot get sick twice – my own anecdotal experience is that I had chicken pox twice as a kid. Rare, but not impossible. And also doesn’t change the fact of immunity for the bulk of the population.

    2. Daniel Barkalow says:

      Only if you think that the cases of reinfection were people who became immune and then lost their immunity at a small positive time. If you think there’s a one in a million chance of clearing the virus without becoming immune, then the reinfection rate will never rise; likewise if you think that there’s a one in a million chance of getting infected despite having an immune response.

      I think a reasonable intermediate model would be that, immediately after recovering, you’ve got a one in a million chance of getting reinfected (but you’re likely getting exposed at that time); after a couple of weeks, you’ve got a one in ten thousand chance of getting reinfected (but only if you’re exposed at that time, which is relatively unlikely). Beyond that, your immunity probably won’t drop significantly, but it may not be very useful against whatever coronavirus strains are around in five years. And if you become immunocompromised, your immunity may still be nominally there, but stop preventing infection at all.

  4. JeffC says:

    Derek, I think you might be missing one of the key points. That paper you reference shows that while the antibodies can be detected at month 5-7, the concentrations are low. Low enough, I worry, to be useless. If the neutralizing antibody titre is too low you’ll get infected, the concentration versus potency just isn’t enough to stop it. We should start to be seeing more and more reinfections in the coming months and that’s what I’m watching out for.

    The implications of this are fairly serious I think. It means herd immunity (in terms of infection) is impossible. Everyone is going to get infected, and potentially multiple times. On the plus side the T-cell response seems to be effective and very very long lived (based on the SARS CoV1 data). So people won’t get disease, but I can see no reason why they won’t be infected and then potentially be able to pass on the virus (maybe not in all cases). Fundamentally, that then means everyone on the planet its going to need to be vaccinated. It’s out of the bottle and nothing can stop it from burning through everyone………..So not panic, but concern……

    1. Michael says:

      Look at figure 2-F in the paper. Samples of every one of the confirmed seropositives, except one, successfully neutralized live virus in the lab. So the levels are almost always not so low as to be useless, yet.

      1. JeffC says:

        I appreciate that they are neutralizing, but if the concentration is insufficiently high it will have little effect. Antibodies still need to be at a concentration to be effective. Otherwise, Lilly etc wouldn’t have to use grams of the stuff to get a clinical effect. So my concern is not that there aren’t neutralizing antibodies, it’s that there aren’t enough. Showing they are neutralizing in vitro isn’t really enough. I really hope I’m wrong, but fundamentally it’s the old concentration versus potency question.

        1. Barry says:

          If the relevant Abs are in circulation, it is because the right B-cells are still on hand, and can express more of these Abs at need.
          Persistent or life-long immunity consists of keeping the capacity to express quantities of the relevant Abs (and to expand the relevant T-cells), not in maintaining high Ab titers forever.

          1. Matthew says:

            So, like with the other endemic human coronaviruses?

          2. Jeff C says:

            I don’t agree (respectfully). The data is showing that the antibody response is reducing, which means the B cell population is reducing. And we still don’t know for sure that the antibody response was sufficient. After all, severe patients appear to have a stronger antibody response than asymptomatics. We can get to immunity from a disease perspective via T cells, but I don’t think the antibody response is long enough lived to prevent rounds of infection, or prevent transmission. We’re no seeing sterilizing immunity I guess is my point.

          3. x says:

            It’s truly frustrating having to constantly explain anamnestic responses to people who have seemingly dabbled in immunology enough that they should already know about them.

            Or perhaps they haven’t dabbled, and are just expertly parroting the news they’ve read, without ever having understood the underlying science.

    2. Liam says:

      >> Fundamentally, that then means everyone on the planet its [sic] going to need to be vaccinated. It’s out of the bottle and nothing can stop it from burning through everyone

      Was this in question?

      The public discourse has been “this isn’t going to die out” for a while now. The vaccine is viewed as getting us back to a relatively normal state of constant vaccinations (see: measles), not eradicating the virus.

      1. confused says:

        Yeah, past flu pandemics didn’t end with the virus dying out – even recent ones when flu vaccination was available. It just became a regular circulating “seasonal flu” virus.

        I’d expect SARS-COV-2 to end up joining the regular cohort of circulating respiratory viruses – “common cold” coronaviruses, rhinoviruses, RSV, influenza, parainfluenza, etc.

        IIRC, isn’t there a hypothesis/speculation that the “Russian flu” pandemic of 1890 was actually the origin of one of the current “common cold” coronaviruses, not a true influenza virus?

        1. Marko says:

          Yep , and the “Russian Flu” has many similarities to the current pandemic. It had a brutal third wave , which we have to be ready for this winter :

          1. confused says:

            Hmm. But I’m not sure historical wave patterns are applicable to today, given very different travel patterns + measures taken.

            Since we don’t even have a clear answer as to why regular colds/flu are seasonal (indoor activities? actual temperature/humidity? vitamin D?), I don’t see how seasonality of COVID is predictable. The summer surge in the southern US seems kind of against strong seasonality… on the other hand we have lots of air conditioning now which we didn’t in past pandemics, except 2009… but I think 2009 did die down in the summer, and places like TX do still see a winter flu season even with air conditioning…

          2. Marko says:

            The four endemic common cold coronaviruses are all strongly seasonal. I’m betting this one will show itself to be one of the gang. It is easy for seasonality to be masked by other interventions , however. The failure of expected flu outbreaks to appear across the globe in 2020 is evidence of the impact NPIs can have.

            As to what causes the seasonality , I’d guess it’s probably as much an indoor vs outdoor social contact phenomenon as anything else , though the dry , heated indoor air is suspected to make the respiratory mucosa more susceptible as well.

          3. confused says:

            Your guess is certainly reasonable — though I do wonder why places like FL and TX still have winter flu seasons when the winter is often more favorable for outdoor activity than the summer.

            But my point is that we don’t solidly know even for well-understood viruses…

          4. Marko says:

            I think most of the seasonal viruses are only considered to be strongly seasonal within the temperate zones. I’m pretty sure that’s the case for the cold coronavirus strains. There’s probably some seasonal infection bleed-over from the temperate areas into the warmer areas due to vacation travelers and such.

          5. confused says:

            Yeah, I guess it could be a consequence of that being the flu season in the rest of the US. I’m just saying… if we had solid answers as to these familiar viruses I’d feel a lot more confidence in predictions for a novel virus…

          6. J N says:

            As far as I know, warm/hot humid air is the enemy of coronaviruses (which are not that delicate under UV). Cool dry air isn’t going to kill coronavirus in a hurry, and, who knows, in addition to enhancing aerosol transmission, fomites might even make a comeback.

            In re immunity and re-infection, personally my opinion will probably a few more months after there has been more time for people to become reinfected, and for the effects of vaccine and mab trials to be better understood.

      2. JeffC says:

        Well on this blog it’s been apparent for a while. But at least in theory with only 10-20% of the population having been exposed, you could anticipate that an effective test track isolate system could eliminate the virus. And a vaccine with sterilizing immunity would also see it eliminated. All of that is still possible. I haven’t see much on the long term prognosis that the virus will be endemic and based on the immune data we’ll be being vaccinated every year for this damn thing.

        1. confused says:

          You’re not going to have worldwide vaccination uptake or worldwide test/trace/isolate, though.

          Sure eradication is possible, as for smallpox, but smallpox was *really deadly*. Once this recedes from pandemic levels & most people have some degree of immune memory I doubt this will be scary enough to drive those measures (tons of people don’t bother to get flu shots).

          And I wouldn’t assume yearly booster shots forever… flu shots need to be annual because of how fast flu viruses mutate, coronaviruses are different. Maybe the first one won’t be, but if so there will be better COVID vaccines. The amount of money/work/intellectual effort put into this is pretty incredible.

          1. Oudeis says:

            Smallpox was also a DNA virus that presumably mutated less than this one. It was less of a moving target.

          2. confused says:

            OK, but my point is that I don’t think the “technical/scientific” difficulty of it will be relevant, since there won’t be the political/social will for an eradication program. Once we have good vaccines & treatments and the population is no longer immunologically naive, I think fear of COVID will rapidly recede.

            In much of the world, there are much more severe infectious diseases (not yet eradicated) than COVID will become post-pandemic/post-vaccine and better treatments.

          3. ProfessorGreen says:

            Smallpox was also– and this is crucial– a disease with no non-human hosts. SARS CoV-2 can cross over into animal populations (see, for instance, If the virus becomes endemic in another host species, the ongoing risk of zoonotic transmission will make it effectively impossible to eliminate.

    3. P says:

      I’m certainly no immunologist, but from what I have read it seems that a pretty steep decline in measurable antibody levels is not a problem, because there remain a repertoire of memory b-cells ready to go in the case of re-exposure.

      My understanding is that this is enough to prevent re-infection in some diseases – can anyone with some actual knowledge chime in?

      1. x says:

        That’s correct, the immune system has memory and can rapidly produce antibodies in response to a familiar antigen.

        The big question w/r/t vaccination and treatment is exactly which part of the immune system is effective against COVID – B-cell antibodies, T-cells, or mucosal antibody (IgA) – and for how long, and how effective they are. AFAIK, jury’s still out on that one.

        Given the relatively low number of reinfections, it’s probably fair to say that people USUALLY don’t catch COVID twice – so I would rather look at the people who did, to see if maybe they didn’t generate much of an immune response the first time; a mild infection might not cause immunity, and people with compromised immune systems (such as the elderly) might not develop immunity either.

  5. Michael says:

    Here’s what the author of one of the articles linked in Derek’s post believes:

    >“We clearly see high-quality antibodies still being produced five to seven months after SARS-CoV-2 infection,” said Dr. Bhattacharya. “Many concerns have been expressed about immunity against COVID-19 not lasting. We used this study to investigate that question, and we found that immunity is stable for at least five months.”

    >When a virus first infects cells, the immune system deploys short-lived plasma cells that produce antibodies to immediately fight the virus. Those antibodies appear in blood tests within 14 days of infection. The second stage of the immune response is the creation of long-lived plasma cells, which produce high-quality antibodies that provide lasting immunity.

    >Earlier studies extrapolated antibody production from initial infections and suggested antibody levels drop quickly after infection, providing only short-term immunity. Dr. Bhattacharya believes those extrapolations focused on short-lived plasma cells and didn’t take into account long-lived plasma cells and the high-affinity antibodies they produce.

    >“The latest time-points we tracked in infected individuals were past seven months, so that’s the longest period of time we can confirm immunity lasts,” Dr. Bhattacharya said. “That said, we know that people who were infected with the first SARS coronavirus, which is the most similar virus to SARS-CoV-2, are still seeing immunity 17 years after infection. If SARS-CoV-2 is anything like the first one, we expect antibodies to last at least two years, and it would be unlikely for anything much shorter than that.”

  6. giannis says:

    “She was being treated with chemotherapy to impair. B-cell production,”

    No need for period before B-cell

  7. franko says:

    I believe health care workers working with COVID-19 patients are dying at a somewhat higher rate than other patients, and I would have suspected that is because of repeated exposure to the virus from different patients. I don’t know why the health care workers would have more trouble than other patients clearing the virus the first time. Those reinfections may be from the same strain if one strain predominates in that locality. But I doubt reinfection is as rare as they are hoping.

    1. Chris Phoenix says:

      Reasons why medical professionals might die at a higher rate include simple exhaustion and higher viral count in the infection event.

      1. Dark Day says:

        I’d guess that it also has to do with pure statistical odds — the chances of a healthcare provider being exposed to multiple cases of COVID over the course of a given day are much higher than those for almost anyone else. Vritually every day at work is a virtual “super-spreader” event if you’re working in a hospital, clinic, or other health care setting with a signifcant number of high-risk patients.

        1. metaphysician says:

          This pandemic has me wondering about how much we all underestimate “the dose makes the poison” with infectious diseases. How much effect dose pathogenic “dose” have on disease severity ( as opposed to probability ), and to what extent does it vary from disease to disease?

          1. x says:

            I don’t know about “we all”, but medicine is well aware that the size of an inoculation affects disease severity and that some pathogens require higher “doses” than others.

  8. Marko says:

    There could easily have been thousands of times more reinfections than the handful that have been documented so far. We simply haven’t been doing the testing ( genomic sequencing ) required to document them. Even so , the rate of reinfection would still be low , for the moment. If reinfections are a function of waning immunity , you’d expect higher rates as time passes.

    If it was possible to survey a big chunk of the 150k or so people that have had their virus strains sequenced (i.e. those submitted to GISAID ) , with individual followup and sequencing upon a second infection , we could accurately determine the reinfection rate , and how it’s changing over time. Right now , we’re just guessing.

    1. gene kalin says:

      I’m a just retired internist. I thought I had the virus in Feb, never tested, and then I had documented Covid 19 in March.

      I can tell you with absolute certainty that if a documented Covid 19 patient gets readmitted with Covid 19, it would be a very big concern and deal! The CDC would know about that case within days.

      I have been very attentive to the related medical literature from all over the world. Reinfection so far is very rare.

      1. Marko says:

        I agree that it’s rare , so far , but it’s not rare like “only 3 cases” in the US. It’s clearly at least in the hundreds , and probably in the thousands. I’m guessing roughly 0.01% of the confirmed US infections reported to date are reinfections , based on the admittedly sparse sample size of 3 confirmed reinfections to date. The basis of this is the fact that only ~0.4% of confirmed infections to date have been sequenced in the US.

        0.01% x ~ 8 million confirmed infections = 800 US reinfections. If you apply that same percentage to total infections in the US , assuming a 10% seroprevalence , you get ~3,300 reinfections. Both of these estimates are undoubtedly lowballs , since I’ve assumed that the 3 reinfections reported represent a complete capture of those reinfected among those sequenced. That’s clearly not the case since many of those who were sequenced could have had a previous asymptomatic infection before they got a PCR and sequence done on what was actually a reinfection , not a primary infection.. Similarly , many reinfections could be asymptomatic , so even if their primary infection was sequenced , they wouldn’t be captured as a reinfection.

        A 0.01% reinfection rate is still rare , but that’s what you’d expect at this point. With the common cold coronaviruses , reinfections are much more common after a year or more.

  9. Barry says:

    He may have fended off the first infections w/ Abs to non-Spike epitopes.
    Or perhaps he fended off the first one because something else (a cold?) had boosted his
    expression of Interferon 1 that week, and innate immunity dominated his (effective) response w/o ever mounting effective Abs.
    Ostler taught us “When you hear hoofbeats think horses, not zebras”. But this re-infection seems to be a rare occurrence, and may just be a zebra.

  10. Shazbot says:

    Personally, finding a very small handful of cases of reoccurrence is a lot more reassuring than finding none. There’s enough variability in both clinical progression and immune responses to Covid-19 that an extremely small number of people may not be fully immune after recovery seemed almost inevitable. These aren’t occurring by the tens of thousands, and there is enough examination to find some of the very small number.

    Thanks for laying it out with so much detail, Derek. Great work as always.

    1. confused says:

      Yeah. Given variability of human immune systems, absolutely zero reinfections from something this widespread (tens of millions of confirmed cases, probably hundreds of millions of total infections) never seemed plausible. (I had chickenpox twice…)

      The more useful question IMO is whether it’s common enough to be *relevant to the course of the pandemic*.

      1. Gene Kalin says:

        Relevant, just not significant – so far in the world.
        Shingles is from the Chicken Pox virus hiding out, and very common in older folks.

        1. confused says:

          Sure, but that (shingles) isn’t reinfection, is it?

        2. Gene Kalin says:

          Same virus hiding out in your nervous system until you are old.

          Actually having Chicken pox itself twice would suggest some serious immune problem.

          1. confused says:

            Well, I don’t know what to say about that. I definitely had chickenpox itself twice — definitely not shingles — and I seem to have a reasonably strong immune system (I basically never get sick, and when I got the 2009 H1N1 pandemic flu it was very mild & brief).

            People are weird and there are always exceptions.

    2. Doctor Memory says:

      Agreed. “Zero” seemed like a red flag for “we don’t have the data / our data is crap.” A consistently low rate is much better news.

  11. Joey says:

    I think it’s not surprising considering extensive social distancing throughout the world, and low prevalence of SARS-2 itself, and SARS-2’s proofreading enzyme and low mutation rate (relative to influenza), that SARS-2 hasn’t experienced much mutation; mutations are roughly linear in the number of infections. Selection pressure for immune-evading variants has been low as well, because immunity has low prevalence and the vast majority of immune individuals continue social distancing. Of course, if immune people are increasingly exposed, for instance “immunity passports” or non-vaccine herd immunity strategies, selection pressure will favor the rise of immune-evading variants which would quickly dominate other variants once widespread vaccination occurs.

  12. Robert Stephens says:

    Millions and millions and millions of swabs have been taken. Now if one happens to get contaminated, and the individual some weeks or months later happens to becomes truly infected,
    how do you think this might be reported?
    Are we not allowed to mention the possibility of false positives in this arena? is this uncool? a dirty word? Not saying that reinfection is not possible but why is there absolutely mention that some of these cases could have been contaminated swabs?
    Have there been any reports of reinfection where the first swab was repeated and verified?

  13. hans says:

    Why does nobody mention memory cells. I was taught, admittedly a long time ago, that memory B- and T-cells produce long term immunity, and not persisting antibody levels.

    1. x says:

      Probably because you have a whole bunch of journalists and peanut gallery types who are trying to sound well-informed and authoritative but don’t actually know the first thing about immunology.

  14. Bill says:

    Not thinking of any particular case, but couldn’t a person get the flu, test false-positive for Covid and be admitted to the roles… And then later get Covid for real?

    1. Bob says:

      I don’t know what “admitted to the roles” means but yes.

      Here are the 4 categories of reinfection followed up with the most plausible explanation:

      1. The “I was sure I had it in March and the swab was positive the second time!”
      means they had flu the first time

      2. Two positive swabs separated by weeks or months.
      means first swab was a false positive

      3. Two positive swabs separated by weeks or months and genomically different(!)
      means first swab was a false positive (contaminated)

      4. Two positive swabs separated by weeks or months: first swab repeated and verified (or clear serum response). Likewise, second swab verified.
      True reinfection (not yet reported).

  15. Dark Day says:

    Meanwhile, more confusion thrown into the mix from “On High” . . .

    1. DataWatcher says:

      I honestly believe that speculation — informed and otherwise — is interesting, but the fact is that we will not know how, whether, or to what extent any kind of mass immunity will develop until we have a vaccine, along with sufficient uptake. There are simply too many unknown variables, including exactly how many undocumented cases there are and/or have been; the extent to which survivors of mild and asymptomatic cases do or do not carry the same load of antibodies as suvivors of more serious cases; whether vaccine-induced immunity is (or isn’t) more robust and longer-lasting than post-infection immunity; the interaction between vaccine-generated immunity and any already-existing immunity in people who have already been infected; age differences; and so much more. We simply won’t know until the vaccine[s] become widely available, are taken by a sufficient number of people, and case-positivity rates either do or do not decrease to a diminishing level.

    2. Hopeful [but confused!] Layman says:

      What exactly do they mean by “allow those who are at minimal risk of death to live their lives normally to build up immunity to the virus through natural infection, while better protecting those who are at highest risk”? Forcing anyone over 60 to stay home in quarantine? Only allowing people who are young and healthy to go to work? Have “reverse age limits” (“55 and under only”) in bars and nightclubs? Most older people are already wearing masks and distancing themselves as much as possible. What more can be done to “better protect” them? And how will we determine which younger people are “at minimal risk of death” in the first place? Black and Latino people of all ages are dying at disproportiontely higher rates, and a lot of other younger people also have pre-existing conditions. I don’t see how this could be operationalized at all.

      1. confused says:

        I think the idea is simply to stop advising young healthy people to take precautions, but still advise older & at-risk (diabetes, heart conditions, etc.) people to? Maybe?

        I don’t think anything coming from the administration will have much effect on what actually happens, anyway, at this point (20 days before an election the incumbent is strongly expected to lose). It’s all being run by the states anyway…

  16. steve says:

    I wouldn’t be so sanguine. There are four seasonal coronavirus that have circulated every year for decades and cause 20-30% of what we call “colds”. We NEVER develop herd immunity to these. There is no reason to think SARS-CoV-2 is different. You cite one study but it stands in contrast to a dozen others that show that neutralizing antibody titers correlate with severity of disease and even in severely diseased patients wane over the course of a few months. There is a lot we’re learning and it’s not at all clear that either natural immunity nor vaccines will confer long-lasting immunity.

    1. Hopeful Layman says:

      Okay, layman’s question — could one reason we never develop herd immunity to the common cold simply be that there aren’t enough infections to bring it about? We never have upwards of 80% of people catching (and spreading) a cold at the same time. For that matter, except in unusual cases like the Spanish flu, we don’t see a critical mass of influenza cases, either.
      Don’t get me wrong — I’m not arguing for an attempt at a “herd immunity” approach to COVID, which in my opinion would basically amount to genocidal human experimentation carried out on a national (or international) scale. I’m just wondering whether the common cold and/or the flu can be discussed in the same context as other diseases which have spread rapidly and widely, and hence have resulted in herd immunity or something close to it.

      The discussions of COVID mass immunity (whether technically “herd” immunity or not) that I think are reasonable and responsible discuss both recovery from cases AND significant uptake of an effective vaccine, along with personal protective behaviors for as long as necessary to help the process along. I believe that’s what we should be focusing on.

      1. steve says:

        The immunity to these four coronavirus wains in exactly the same manner as it does with SARS-CoV-2 and reinfection is common. I suspect that reinfection with SARS-CoV-2 is common as well and that we just don’t have long enough experience with it to see it yet. See

      2. Barry says:

        The “common cold” is not one disease. It is caused by a constellation of viruses including strains of rhinovirus, of parainfluenza, of RSV and many more, all unified by symptoms, not by etiology. It’s not easy to define a “species” of virus (and may not even be appropriate to use that language for a virion that’s neither sexual nor alive). But individual strains of these viruses are driven out of circulation all the time as the host population develops immunity. The “common cold” comes back not because of re-infection w/ the same strain, but because viruses mutate (coronavirus mutates more slowly than many) and eventually escapes heterologous immunity.

        1. steve says:

          Barry – you didn’t read what I wrote before you responded; you might want to do so as well as read the article I posted. Marko, no we don’t have heard immunity to the four seasonal coronaviruses, it’s explained in the article I quoted. For the others, the Spanish flu hit a younger demographic than coronavirus. The Spanish flu killed by inducing a cytokine storm; early on it was thought that COVID killed in the same way but it now appears more due to a dysregulated immune response and a remarkable coagulopathy than a true cytokine storm.

          1. Marko says:

            You need to read and understand my post. It is not inconsistent with the article you posted. I defined what I meant by “herd immunity” for the common cold varieties as representing protection from severe disease , not infection , because the more dangerous episode of infection with these strains occurred in a naive population in the distant past , while in the current population sufficient immunity exists from childhood on such that a cold is the worst outcome for most once they’re once infected.

            For some part of the current population , COV2 may already be the fifth common cold variety , simply by virtue of their immunity to the other strains. If we can get to that state with a vaccine that protects the vulnerable , COV2 would be no more of a threat than the other four strains going forward.

          2. Barry says:

            But for the viruses closest to SARSCoV2 (MERS and SARS) survivors (at least survivors of serious infection) so seem to have durable immunity years later

      3. Marko says:

        I think we may have a sort of herd immunity to common cold coronaviruses , in the sense that they rarely cause more than a cold. All four of those strains may have caused severe disease and mortality at some rate in elderly populations when the first crossover from animals to humans occurred , i.e. when each strain was truly novel to humans. The susceptible elderly either died or survived with lifetime protection against anything worse than a cold , by virtue of the original exposure as well as subsequent “booster” exposures”. Children , as for COV2 , were largely spared and also developed lifelong protection against severe disease. Every subsequent adult generation was once a child that got that immunity in early life , so the strains never caused severe disease again , even many decades later , because there were no naive elderly left to infect.

        If COV2 similarly becomes just another endemic common cold , that’s a win , as long as it happens after the susceptible are protected by a vaccine.

        1. Hopeful Layman says:

          Hasn’t it been postulated that that’s exactly what happened with the Spanish flu?

          1. Barry says:

            It’s now thought that the peculiar mortality distribution of the 1918 “Spanish flu” pandemic was because survivors of an earlier (1872) H1N1 pandemic (starting in Toronto) still had immunity. But anyone under 40yrs old was naive.

          2. Marko says:

            As Barry said , that was a little different , but there’s a possibility that this scenario unfolded after the 1890 “Russian flu” , which may have actually been caused by one of today’s common cold coronaviruses. See this : ( you’ll need to run it thru Google translate)


        2. steve says:

          Barry – you didn’t read what I wrote before you responded; you might want to do so as well as read the article I posted. Marko, no we don’t have heard immunity to the four seasonal coronaviruses, it’s explained in the article I quoted. For the others, the Spanish flu hit a younger demographic than coronavirus. The Spanish flu killed by inducing a cytokine storm; early on it was thought that COVID killed in the same way but it now appears more due to a dysregulated immune response and a remarkable coagulopathy than a true cytokine storm

      4. Kenny says:

        “Herd immunity” doesn’t mean that a virus can’t spread. It just means that enough people are immune that the average sick person only infects one other person before recovering. It means that instead of going up in flames, the epidemic burns slowly like a cigarette. If a given virus needs 60% of the population to be immune to reach herd immunity, and if immunity is permanent, then that means that in the long run, if there are 4 million people born every year, there will be 2.4 million new infections every year. (These infections will be more common in young people, but they will occur at all ages, in proportion to the number of people of that age that haven’t reached immunity yet.) When the population is at this level, you’ll occasionally have small outbreaks, alternating with some waning in the number of cases, but you’ll never have 10 million new infections in a single year (let alone the multiple tens of millions of infections that we had in this year with covid).

        There are several dozen “common cold” viruses, so if each one infects 2.4 million people a year, then that could easily explain the frequency of common colds. Even more so if some of these viruses mutate fast enough that immunity isn’t permanent – if people lose immunity, then instead of infecting 60% of the number of births every year in the steady state, it will infect 60% of the number of births plus people who lost immunity.

        1. Irene says:

          There are over 200 viruses that cause the “common cold” constellation of symptoms, per

    2. theasdgamer says:


      We don’t have absolute sterile immunity to the coronavirus colds, but we have substantial partial immunity to them. They don’t kill many people.

      1. steve says:

        Adsgamer – No, they don’t kill because they attack different receptors and don’t have the same genetic makeup as SARS-CoV-2. Over time viruses attenuate; it’s really unsuccessful viruses that kill their hosts. Evolutionary forces tend towards reduced pathogenicity. Again, we don’t have immunity to them, they re-infect us all the time. Please read the article I posted.

        1. Ian Malone says:

          Except SARS-CoV-2 has little evolutionary pressure to reduce its fatality rate (it doesn’t kill that many of the people it infects and doesn’t kill them until quite a while after they’ve become contagious), and neither do we (since it mostly kills older people, also waiting on human evolution to fix something is slow).

          1. Dark Day says:

            Either way, we can’t afford to “wait” for evolution to save us. We need to focus on exactly what most folks here would say makes sense: Developing good and effective vaccines and treatments, and continuing to engage in heatlhy preventive behaviors (you know the drill!) to tide us through in the meantime.

        2. theasdgamer says:

          I stopped reading after coronavirus infections are often asymptomatic and viral shedding is limited.’

          Indistinguishable from herd immunity?

          1. Hopeful Layman says:

            This is a question I have had for some time. If viral shedding is really “limited” in asymptomatic carriers, then is if feasible to postulate that even if 40% of all cases are spread by asymptomatic carriers, the vast majority of these are also either asymptomatic or mild? I guess I’m projecting onto the predictions that a vaccine might provide a kind of “partial” immunity, whereby people would still contract the disease, but it would be an either mildly symptomatic or possibly asymptomatic upper-respiratory infection. Do we have any actual data on WHICH cases result in the most serious infections when they spread?

  17. Dark Day says:

    Another question. As of now, pregnant women are not included in the trials. That’s a LOT of people who won’t qualify for a vaccine — enough to seriously impair uptake, even if “hesitancy” diminishes duirng 2021? How serious might this be?

    1. Barry says:

      And in the U.S., children–who cannot give legal consent–are routinely excluded from clinical trials. But once a vaccine has the FDA’s approval in other age brackets, it will be available–and reimbursible–for pediatrics, I think.

      1. Dark Day says:

        A lot of parents won’t consent to have their kid jabbed with a vaccine that hasn’t specifically been tested on children.

    2. confused says:

      I don’t see why… not that large a % of the population is pregnant, and a pregnancy only lasts ~9 months so they would be eligible for vaccination soon…

  18. Karl Pfleger says:

    These folks with 2nd infections seem very well studied. It’d be nice if someone measured their vitamin D levels. Ideally, I’d like to know the 25(OH)D between infections (before 2nd infection starts).

  19. Mister B. says:

    A case (woman, 37 y.o., two positive tests in 5 months, symptomatic) is currently being studied in Montreal.

    Warning. The genetic sequence hasn’t been done yet. Confirmation of a second reinfection cannot be done.

  20. Marie says:

    I’m a long hauler and belong to a Facebook group with thousands of my peers, and we’ve already seen at least a dozen reinfections (positive in March or April, then negative for months, then suddenly positive again now with a return of the original symptoms). None of these people get the full test that looks at the genetic markers of the virus, so they’re not being studied, or more relevantly, COUNTED. Trust me, reinfections are occurring everywhere, and just like they didn’t talk about us long haulers for months because we were vastly ignored and called hysterics, doctors aren’t paying attention to these second infections the way they should yet. Good luck to us all.

    1. DrivingToCuba says:

      What is the age distribution in your long-haul group, if I may ask? I am interested bc I’m in a high risk group, etc.

    2. theasdgamer says:

      I’m curious whether any long haulers were treated with HC or ivermectin within 5 days of symptom onset.t

  21. Valdis Andersons says:

    For some reason this pre-print hasn’t gained much attention at all, even though there is genome sequencing for both the 1st and 2nd episodes:

    They followed up a little over 130k confirmed cases and checked how many had 2 positive tests at least 45 days apart. From the results section:

    “Viral genome
    sequencing confirmed four out of 12 cases with available genetic evidence. Risk of reinfection
    was estimated at 0.01% (95% CI: 0.01-0.02%) and incidence rate of reinfection was estimated at
    0.36 (95% CI: 0.28-0.47) per 10,000 person-weeks.

    1. Marko says:

      Interesting. They came up with the same reinfection rate ( 0.01% ) in Saudi Arabia that I derived ( comment further up above ) for the US using a crude estimation :

      Reportedly , only 0.4% of confirmed infections in the US are sequenced , so we are only capturing , at maximum , one of every 250 cases of reinfection. The BNO reinfection tracker shows 3 reinfections reported for the US so far. Thus , you’d expect the actual number to be 3 x 250 = 750. 750 divided by 7.5 million confirmed infections = 0.01% reinfection rate.

      1. Marko says:

        My mistake. It was Qatar , not Saudi Arabia.

  22. What peak viral load is still achieved in a fresh infection of someone who already has long-term immunity to covid? i.e. even in someone who is appropriately immune due to exposure to the wild-type virus, is it possible they could register positive on a PCR test while their body is remounting its specific immune response?

  23. Tuck says:

    So three people have been reinfected, as covered above.

    However, Covid-19 is similar enough to other CoV that up to 81% of people have been found to have some level of immunity against the “new” version.

    “Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection.”

    So what about reinfection?

    It would be reasonable to expect that this virus would also be similar to the other versions, as it’s similar in almost every other way.

    Unfortunately, reinfection is common in the other CoV.

    See here:

    “In OC43 infection, a serum hemagglutination inhibition anti-body titer of >=40 was associated with protection… against reinfection. Nevertheless, 43 per cent of men who became infected with OC43 virus had initial serum antibody titers of >= 20 and < 80."

    43% is pretty high. And here:

    “Researchers have studied four species of these seasonal coronaviruses across the past 35 years, and found reinfection occurred frequently, around a year after the first bout.”

    And here:

    “Neutralizing antibody to 229E was commonly present in the sera of the students. The level… did not appear to influence the occurrence of, or likelihood of illness with, reinfection… underscores the natural occurrence of reinfection with this virus.”

    So yes, we’ve only seen three people get reinfected with the new virus.

    But there’s no reason to think this will be rare. It should be quite common, especially as this virus becomes endemic, as I expect it will.

    It will be interesting to see if a vaccine is possible…

  24. li zhi says:

    It’s hard (and almost never productive) to argue with “Don’t Panic” advice. OTOH, I’m quite dubious that we have had the extensive testing to quantify nor that the medical community has been actually looking for re-infections. I know of 4 people who believed they had covid-19. One was hospitalized/ventilated, one has refused to be tested, and 2 had negative ab tests, months after they were sick. Given that it is likely that the clinicians haven’t been looking for re-infections, and that testing in the USA has been lacking, I wonder how rare re-infection actually is. I also wonder why being re-infected but with both strains having unchanged spikes is a positive sign. Doesn’t it mean that *if* the spike was immune system target that its response wasn’t effective? It seems to me you could argue it either way, depending on your priors. I’ve zero medical expertise.

    1. confused says:

      >>I also wonder why being re-infected but with both strains having unchanged spikes is a positive sign. Doesn’t it mean that *if* the spike was immune system target that its response wasn’t effective?

      Maybe because “very occasionally people’s immune responses don’t work right” has way less implications for the rest of the population/overall course of the pandemic than “the virus mutates to evade working immune response”?

      Not an expert either.

  25. PM says:

    What is likelihood or not of immunity if one received the exogenous monoclonal cocktail with no evidence of an endogenous antibody response, but one has lung inflammation suggesting T-cells brewing, but also taking immuno suppressant dexamethasone? Asking for a non-friend of humanity.

  26. Marcus Theory says:

    Hi Derek, what are your thoughts on the recent Pfizer J Med Chem paper,

    (Disclaimer: I am not now, nor have I ever been, a Pfizer employee! Just interested to hear your take).

    1. Derek Lowe says:

      TBH, I’m not (for the moment) paying much attention to the from-the-ground-up small molecule attempts like this one. I think that the only way they’ll be relevant in the current pandemic is if all the vaccines fail (God help us). Once the dust settles, it’s worth talking about antivirals in general, for the next coronavirus, though.

      1. Barry says:

        The very broad, very expensive ground-up HIV small-molecule efforts taught us most of what we know today about anti-viral therapeutics. But they took years, and only got as far as it did because vaccine efforts all failed.
        It is likely that there will be a safe, efficacious vaccine for covid. And from that effort, we’re likely to emerge understanding vaccines (maybe against TB?) much better.

  27. DataWatcher says:

    RE: The discussion / debate on who should have priorty for a vaccine when it becomes available —

  28. Tuck says:

    Derek, can you moderate comments on this post, please? I think mine is good…

    1. Marko says:

      What’s so good about censorship ?

      Grab your smelling salts and tough it out , like the rest of us.

      1. theasdgamer says:

        It’s always good practice to separate baby from bathwater. Good for the mind.

    2. Derek Lowe says:

      I only clear out the most useless ad hominem stuff. . .

      1. theasdgamer says:

        Even though I frequently disagree with you, I have to admit to your utter coolness in not censoring me.

        1. Derek Lowe says:

          I disagree with you quite a bit myself, and I worry sometimes that you need another hobby other than leaving comments here, but you’re mostly within the bounds of argument. The only stuff I clear out (other than spam) is sheer ad hominem stuff with zero signal/noise.

  29. Digibom says:

    thats very good

  30. BF says:

    Thanks the detailed explanations on complicated topics, as well as the subsequent informative comments.

  31. Hopeful Layman says:

    Definitely a layman’s question, and it’s probably so elementary that I should be embarrassed — but my understanding has been that if the R0 is below one, infection rates will decrease and — if the pattern continues — the pathogen will diminsh and eventually become very rare. But now I’m hearing about states like Wisconsin, where the R0 is 0.99, but the test positivity rates and the overall number of cases continue to rise. What am I not understanding here?

    1. confused says:

      Yeah, I’ve seen quite a few places where the R0 seems to be out of step with what cases are doing.

      But where are these R0 numbers coming from? There must be a model involved since

      And are these “same-day” R0 or some kind of rolling average? I guess if it’s like a 7- or 14-day average they could be briefly “out of step”.

      1. Dark Day says:

        . . . Not to hijack things, but just as a kind of coda to our previous discussion (which is actually related to this one, because it’s about infection and its implications for public safety and public policy) — Today I had a conversation with the chairman of our city’s Office of Special Events, which plans festivals and other events throughout the year (I have served on some of the festival committees in the past). He said that the festival committees will probably start to meet again sometime in the spring, but that there won’t be in-person meetings; all Zoom. He said the city is pretty much trying to get rid of in-person meetings permanently because they want people to be able to meet “safely.”

        I don’t think he realizes the implications of this — if it’s never going to be “safe” for a dozen people to meet face-to-face in a room, then it’s certainly never going to be “safe” to have a festival (or a book fair or any other large gathering), nor will it be “safe” to have live arts and entertainment in clubs, theaters, etc. I don’t know the plans are for sporting events, but if what he said holds true across the board, I can’t see stadiums opening up fully, either. If, as he seems to think, our future will consist primarily of sitting at home staring into screens instead of gathering together in person, this whole business of planning festivals and events (to say nothing of reopening clubs and other performance venues) is basically a lie we’re telling ourselves.

        It will all depend on the numbers, of course, but the predictions from on high look pretty grim right now.

        1. Bill says:

          Is there actual data on infections clearly attributed to outdoor activity? I’m thinking of things like Sturgis which was an outdoor event, but what did they do at night, where did they sleep, did they tow their bikes in a big trailer with a crewcab full of people?

          Same with all the protests. I’d bet all of them had indoor social activity off hours.

          Bleachers and stadiums certainly put people together. But ventilation standards don’t get any higher. Not suggesting I know the answer — just wondering.

          1. Dark Day says:

            I think the Rose Garden event has been identified pretty positively as a superspreading event. You might be right about Sturgis, though, it’s hard to tell — those folks were hangingn out in bars and other indoor areas when they weren’t walking or riding through the streets — and I do remember that a lot of people remarked on how the BLM protests didn’t seem to result in any noticeable spike in cases (although a lot of those people were masked, also). I don’t recall seeing any data about other street protests, demonstrations, etc.

            I do remember reading of a party in a marina somewhere, where boat owners got together and hung out for a day or two, and which resulted in quite few cases. (Can’t recall the details about that one, now).

            And it’s probably the case that “indoor” / “outdoor” is only part of the picture, anyway. Assuming that because of ventillation it’s almost always safter to be outdoors no matter what you’re doing, there are some things that it’s dangerous to do in either setting. The people in the Rose Garden were photographed talking closely face-to-face, hugging and handhaking, etc. I’m sure the Sturgis bikers were doing the same things. Those would be risky behaviors anywhere, ventillated or not.

            On the other hand,outdoor stadiums and arenas, as well as mass events like festivals, are closely packed; people are yelling and shouting (often directly into one another’s faces); they’re eating and drinking (i.e., unmasked); even with good ventillation, they’re at pretty high risk, high-fiving, hugging, etc. It would be a lot more dangerous if they were indoors, but from what we know about the spread of the virus, the things they’re doing in the outdoor setting are plenty risky enough. Which leads us to the question, of course — even when/if things get “safe” enough for relatively “normal” everyday activity, at what point will mass gatherings such as these (as well as closely-packed indoor activities in gyms, bars, arenas, etc.) be considered safe? Will they ever?

          2. confused says:

            >>at what point will mass gatherings such as these (as well as closely-packed indoor activities in gyms, bars, arenas, etc.) be considered safe? Will they ever?

            They will be, and I’d say probably before this time next year, except possibly in a few places like NYC.

            But it also depends on what you mean by “considered safe”. Do you mean “below some particular objective threshold of COVID risk”, “allowed/recommended by public health authorities in a particular jurisdiction”, or “generally accepted by a large majority of the population”?

            These are three very different things.

            Vaccines and better treatments (and “natural” immunity, if reinfection stays rare) will reduce actual risk.

            Familiarity will reduce perceived risk (new risks are scarier than familiar ones). Political/social shifts may affect this — I would expect a general “de-escalation of emotions” in the US if Biden wins the election, as seems the more likely outcome.

            And frustration/desire to go ‘back to normal’ will likely increase acceptance of risk.

          3. Irene says:

            IIRC the Rose Garden event was also not totally outdoors.

        2. confused says:

          >>I don’t think he realizes the implications of this

          Of course he doesn’t. People aren’t thinking that far ahead.

          >>It will all depend on the numbers, of course

          It really won’t. It will depend on people’s *reaction* to the numbers, which is going to be influenced by a lot of things outside what the numbers actually *are*.

          Political and economic realities will get involved. In say July 2021 when Texas and Florida are functioning basically exactly as they did in July 2019, and the deaths have been brought down dramatically by a vaccine and likely better treatments, and COVID cases probably aren’t being closely tracked anymore… it will be really hard for the state governments of Illinois and New York to justify keeping measures in place.

          Telecommuting and tele-meetings will probably remain a lot more common than they were in 2019… because they *should* have already been, and it was basically business-culture inertia preventing it. Lots of people want that. But the end of any kind of mass entertainment events… no way.

          1. Dark Dat says:

            The virus doesn’t care what people’s “reaction to the numbers” is. It simply does what it does, and it will keep on doing it for as long as it can. Just let a big festival happen, followed by a Sturgis-like outbreak (multipled by thousands, most likely, given how many people attend big festivals in the U.S.) , and see what the fallout will be. It’ll be catastrophic on the human level (the most important) as well as the political and economic levels. T

          2. Dark Day says:

            The only way it won’t “depend on the numbers” is if we, as people, stop caring about those numbers. When become oblivious to the suffering and death of our fellow human beings (as well as ourselves), we can all just go about our business as if it doesn’t matter. Given what we’re seeing at Trump rallies, maybe we’ve reached that point already, but I certainly hope not.

          3. confused says:

            I think that by mid-2021 vaccine uptake and likely improved treatments will reduce the *objective* risk to the point it’s not much different than doing those events during a bad flu season, which we do.

            That’s maybe a 5x reduction in risk from where we are now? (Depends on how much you think the IFR has changed since spring…)

            That seems pretty easy when you multiply together …
            (reduced risk of infection from vaccine) x (reduced risk of death, given infection, from vaccine) x (reduced risk of death, given infection, from improved treatments).

            Plus any reduction in risk from “naturally-acquired” immunity by then…

            Assuming this happens, that’s when public perception becomes important.

            [Also, people did in fact go about normal life when much-worse infectious diseases were endemic in the US… But I don’t think *post-pandemic* COVID will be all that bad, just as post-pandemic H1N1 wasn’t after the ultra-deadly 1918 pandemic.]

          4. confused says:

            IE – right now it is correct to treat COVID risk differently & more seriously than other risks of ‘everyday life’, both infectious (eg flu) and other things that can affect people besides oneself (eg car accidents), because:

            – the risk is currently a lot larger: ~220k US COVID deaths in roughly 7 months (first US death was Feb, but numbers didn’t rise until Mar), vs. ~30k US deaths in average flu season, ~60k in really bad one like 2017-18, over maybe 5-6 months; ~33-36k+ US car accident deaths/year)

            – there is a very good prospect that the risk will drop dramatically in the near future due to vaccines & treatment (eg monoclonal antibodies)

            Neither of those things will be true once vaccines are widely-distributed & treatments improve, so there will no longer be reason to treat COVID differently from other risks of everyday life.

          5. J N says:

            Thinking that mabs will be available to people who need them in a safe, orderly manner at low (zero) cost during the current administration is fanciful.

            If the current guy wins again, we’ll see the usual big pharma approach of market-stretching differentiated pricing and making as much money off people who don’t want to die as is possible.

            If the new guy wins, who knows, but nothing’s going to happen until January at least.

            I don’t think people understand how little of the promise from the current guy was and is real:
            * under control: No
            * just wash away, etc.: No
            * vaccine by early November: No
            * effective therapeutics this year: Not quite yet

            For next year, there should be several vaccine candidates and several mabs, and maybe a random repurposed small molecule, but with 100Ms of doses to make and booster vaccines so far, mid-2021 seems pretty optimistic for a fundamental change in the current situation.

            The only way we can fix this, for now, is to get the community prevalence down, and that’s not going to happen with the current guy in charge, unless this coming spike gets to something obviously intolerable like 3000-5000+ deaths/day. (2500 dead/day was NBD earlier in the year, apparently.)

          6. confused says:

            Oh I wasn’t thinking of “during the current administration”. But current projections have Biden quite favored to win, so that’s likely to be only 3 months.

            >>2500 dead/day was NBD earlier in the year, apparently

            It’s not really that… People *were* very scared *in the places that it was happening*. But the March-April spike that was over 2000 deaths/day 7-day average was very localized: mostly just the Northeast, with a few pockets elsewhere (New Orleans and a couple Midwest cities, I think).

            So lots of other places in the US, especially central-US ones that are relatively rural or small-city/low-density compared to NYC/Boston, didn’t really “get it”.

            And even then, many of them did do stay-at-home orders, etc., in late March and early April. The places that didn’t were largely extremely rural sparsely-populated ones.

  32. Marko says:

    It’s the rate of increasing cases that should be declining over time with an R0 of less than 1. Over time , the rate of increase will go negative , and new cases will start declining in absolute terms. At an R0 of .99 , however , that could take quite a while , especially if it follows shortly after a period of relatively high R0.

    A major caveat is that estimating R0 is more of an art than a science at this stage, especially so for the real-time estimates.

    1. Marko says:

      Here’s a graph of R compared to cases in Singapore ( couldn’t find anything similar for the US ):

    2. Hopeful Layman says:

      Ah — many thanks. I guess this is why some people remain optimistic that a decent vaccine (even if it’s not a world-beater of 85+ percent efficacy) that enough people take, along with whatever imumnity has already been established by people having been exposed to COVID, as well as continued public health practices ( masking, distancing, etc.) for as long as necessary, can combine to bring the pandemic under control.

      Let’s hope . . .

    3. Hopeful Layman says:

      I think this might be a related question, and it’s one I’ve been thinking about quite a bit lately. When/if a vaccine is rolled out, it will take a lot longer for its effects to be felt if infection rates are high, right? In other words, if things keep going the way they are now, with the numbers spiking and reaching record levels in quite a few places, a vaccine will have more of an “uphill battle” to be successful than it would if the “curve” was closer to “flat”. Is this a reasonable premise?

      1. confused says:

        Wouldn’t it depend on how effective the vaccine is?

        I mean, if a vaccine – hypothetically – reduced infection by 50% and risk of death *given infection* also by 50%, that’s a 75% reduction in risk of dying. It’s not just a matter of “herd immunity” suppression of R in the population as a whole, it’s also protecting those individuals vaccinated.

        So if the vaccine works reasonably well in older people, and older people are vaccinated first, you might see major drops in death rate even when a small % of the population is vaccinated (since such a disproportionate number of the deaths come from the oldest small % of the population).

        Although given infection -> death lag and death -> reporting of death lag it wouldn’t be all *that* quick.

        Or am I missing something?

      2. Marko says:

        I’m kind of in the same camp as confused , here. I don’t have high expectations that the vaccine will nip the “infection epidemic” in the bud , but I hope it will the “death epidemic”. In that sense , I don’t think the infection dynamics at the time of vaccine roll out are critical , though the lower the rates , the better , obviously. More important is how quickly we can get the vulnerable groups vaccinated.

        Later on , once the wider population is vaccinated , and assuming reasonable efficacy and uptake , perhaps the “R” and infection rates will drop far enough that we can resume normal life , even if the virus is never effectively exterminated. Just look at New Zealand. The virus still pops up there occasionally , but the numbers are so low that they can squelch any outbreak without strict lockdowns and restrictions , even without the benefit of a vaccine.

        1. confused says:

          Yeah. Post-pandemic COVID is likely to be “just another respiratory bug” like flu, parainfluenza, common-cold coronaviruses, etc. If death rates drop enough, people will care no more about infection rates than they do with any of these. This may just end up being the 5th “common cold” coronavirus once there’s a high level of immunity in the population.

          Immediately after the 1918 pandemic, was flu any worse than before it? (and that was even without vaccines…)

          I think there’s a “recency bias” where we take this to be some huge game-changer forever because it’s The Big Issue *right now*.

          1. Dark Day says:

            Not only death rates need to fall precipitously, but so do the rates of cases with severe / debilitating symptoms — a tougher nut to crack, most likely. Obviously, a good, effective, and widely available, treatment is the key to that; we’re seeing some promising candidates, but nothing has emerged as yet. (Also important will be the effectiveness of a vaccine on older people; today, unlike ca. 1918-1920, people over 60 – 70 years old fully expect, and are expected, to have at least ten more years of relatively active and robust life in them. They’re part of everyday public life in ways that they weren’t necessarily 100 years ago — the proverbial “old man on the park bench” is now playing handball, jogging, dancing at the nightclub, or going on a hot date with his new flame! So we may have a somewhat more challenging task in terms of getting to the point where “most” people feel safe living what they consider to be a “normal” life. “Old” folks aren’t going to be content to be put on the shelf.)

          2. confused says:

            >>Not only death rates need to fall precipitously, but so do the rates of cases with severe / debilitating symptoms — a tougher nut to crack, most likely.

            I would think even an imperfect vaccine would do that too… the discussion regarding ‘sterilizing immunity’ vs lesser immunity on this blog has been that it might reduce it to a ‘regular upper respiratory infection’ but not prevent it from spreading to unvaccinated people.

            So it ought to reduce hospitalization/ICU level cases as well as deaths.

            I am very far from an expert, though.

          3. Dark Day says:

            Does anyone know whether those predictions that a vaccine could reduce COVID to a relatively benign upper respiratory infection applies to the elderly and other high-risk groups? I admit that’s my biggest worry, and I also admit some self-interest here since I”m over 65, and most of the people who are dearest to me in my life are in their 50s and older AND happen to be people of color. So, as much as I’m glad that younger, more robust folks will probably fare very well after a vaccine is rolled out, I’d hate to live in a world where only the relatively young and robust could feel safe engaging in everyday activities.

          4. Marko says:

            “Does anyone know whether those predictions that a vaccine could reduce COVID to a relatively benign upper respiratory infection applies to the elderly and other high-risk groups?”

            It wouldn’t be worth much as a prediction unless it did apply to that group. COVID even without a vaccine , for the vast majority , is a relatively benign upper respiratory infection unless you’re in the elderly/high risk groups.

            When you get to a certain age or degree of frailty , even a flu or common cold can set off a chain of sequelae that ends with death. Most people live their lives happily right to the end while facing that possibility. You get your flu shot and you do the best you can to protect yourself , but you don’t obsess about catching a cold to the extent that you stop enjoying life. A vaccine may well put COVID in that same category for those higher-risk groups. Look forward to that possibility , rather than assuming the worst.

            A Brighter Day may be just around the corner , Dark Day.

          5. Dark Day says:

            Well, Marko, I will say that over the past year we’ve heard a lot of optimistic predictions, virtually all of which have pretty much crashed. Optimism hasn’t had a good year. So, I think a lot of people are leery of thinking there might be a light at the end of the tunnel — might be a train coming at us!!

        2. Hopeful Layman says:

          Yes, I’ve been thinking about New Zealand. If there’s anyplace that has a chance of being able to officially declare itself “COVID-free” after a vaccine is introduced, that’s it. Of course, they’ll still have to be really vigilant about people coming in from countries where things weren’t done as well (umm . . . know any countries like that?.). I think right now all people entering New Zealand from abroad actually have to be quarantined. That probably won’t go on forever, but it wouldn’t entirely surprise me if they enacted an “immunization pass” pollicy of some kind, probably a proof of vaccination required (for adults, anyway) to enter the country. For that matter, I wouldn’t be surprised if some Asian countries did the same thing.

          p.s. If Trump would like to see what happens when the leader of a country takes strong, proactive measures to head off a public health catastrophe like COVID, he only has to look at the headlines from New Zealand about the record landslide victory Prime Minister Jacinda Ardern just won in the country’s election.

          1. theasdgamer says:

            When it comes to pandemics, island countries have it a lot easier than continental countries, in general.

            Don’t underestimate the ability of public health authorities to screw things up royally. UK comes to mind.

  33. blogreader09 says:

    New Zealand’s time “in the barrel” is coming. The “strong protective measures” (warmly approved of by the control-loving morons of the left) are doing way more harm than good there.

    1. Dark Day says:

      New Zealand just had its first COVID case in three weeks. Obviously they’re still at risk and will be at least until a vaccine is rolled out, but they’ve come as close to eradicating COVID as it’s possible to get without a vaccine. So how, exactly have”strong protective measures” done “more harm than good” there? What, exactly, would you recommend instead?

      1. J N says:

        The restrictions, even “lockdown,” in AU-NZ are not incredibly severe. In fact they are middle-of-the-road by US standards.

        And, obviously, in areas where spread is being successfully managed, restrictions are pretty light.

        People are just going to have to adjust to get through this, because the virus won’t.

    2. RAB says:

      I must amit to being a tad confused by this comment. I’ll have to have a closer look around tomorrow as currently I don’t feel more harm than good while I’m out and about. No restrictions on what I do or where I go. Resturants and bars are busy. Crowd of 40,000 for a rugby game last weekend. Things seem to be pretty normal down here. I guess we just have to suffer through competent leadership from a pack of “control loving morons of the left”. Seems to beat the crap out of a lot of other places around the world.
      (oh and if I see a barrel I’ll try to avoid getting in)

      1. theasdgamer says:

        See, first you have to create an island. Most all the places doing exceptionally well are islands.

        The exceptional non-island case is Utah. But nobody wants to talk about them.

        1. confused says:

          Utah is spiking now I think.

          But yes it was hit surprisingly late… I think Utah is a bit of its own thing though, not as much a tourist destination as neighboring Nevada or Colorado (though obviously they have some skiing etc.)

          Islands doing well isn’t really surprising… The surprise to me is the difference between tropical Southeast Asia & Africa (relatively low death rates) and tropical Latin America (relatively high death rates). Population age structure might be a factor here, but…

          1. theasdgamer says:

            Utah recommends using Zelenko’s protocol on its state health dept. website–Hydroxychloroquine, azithromycin, and zinc.

            Hydroxychloroquine is cheap. Africa can only afford cheap drugs and doesn’t have public health authorities amenable to US pressure. You can get HC over the counter in Africa and don’t need to see a doc. Cheap, effective, overthecounter meds are good for Africa.

            We in the west prefer expensive, ineffective, prescription meds. We are so much more advanced than Africa. lol

          2. Derek Lowe says:

            Link the Utah site? When I go to and search “hydroxychloroquine” I get zero hits.

          3. theasdgamer says:

            Utah has had a lot of cases and not too many deaths. Lowest cfr of any state and competitive with African countries. Utah has a young population compared to US states, but much older than African countries and Latin American countries.

            When looking at Utah’s success, consider that their 85+ ifr is only 10%, which is exceptionally low for that age group. For comparison purposes, the ifr for 80+ in my county is 25%.

            Utah has a low percent of blacks, but their nonwhite percentage is 30%, which is substantial.

            It’s not blowout evidence for hydroxychloroquine, but it’s strong.

          4. theasdgamer says:


            Hydroxychloroquine is mentioned in a pdf linked on the Utah site.


  34. blogreader09 says:

    Virtually zero immunity in your population and a highly contagious virus charging relentlessly back and forth across most of the planet. Good luck with that, mon ami.

    1. theasdgamer says:

      Virtual zero immunity apparently produces 40% asymptomatic cases of covid and another 40% mild cases.

      Maybe we need less immunity. lol

      It’s only academics that can produce such bilge.

  35. Marko says:

    Some evidence of OAS ( original antigenic sin ) in Covid patients with pre-existing immunity to other coronaviruses :

    “Antibody Immunological Imprinting on COVID-19 Patients”

    Not clear as yet what practical impact this has on the clinical course of disease or on immunity to Cov2 acquired from infection or vaccines.

  36. Hopeful Layman says:

    The issue of transmission via aerosol droplets is still up in the air (pardon the expression)??

  37. theasdgamer says:

    Even late, our experience might be valuable to some. It’s hard to pick when you’ll get infected.

    My 3-generation household experienced a covid reinfection. Because _I_ was prepared, we cleared symptoms in 24 hours the first time and 8 hours the second time.

    We didn’t bother seeing any doc or getting tested. The symptoms were typical of covid–general fatigue, severe headache, dry cough, nausea/vomiting. The baby never showed any symptoms either time, which indicates that the infection wasn’t flu. So we suspect covid. (My wife never goes out, so she had to get it from one of us.)

    We treated with large doses of vitamins C&D & zinc & EC (elderberry concentrate, which contains quercetin). My wife was dilatory about the EC because she was skeptical about it, but our daughter convinced her to take it. After she took it, her symptoms started clearing.

    Except for my wife the first time, we started treating the same day as symptom onset. First infection, my wife started treating the second day. My wife and I are 65+ with significant comorbidities.

    We monitored our O2 levels with a pulse ox, just to be safe.

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