What is the reasoning behind "we expect with high certainty a “flu-like drift” of SARS-CoV-2" ? It seems like everything you said (and I've read elsewhere) is that viral evolution hasn't fit any known models or patterns. Omicrons BA.1 and BA.2 are as different from each other as Alpha, Beta, Gamma, and Delta are from one another, so that isn't ladder like change yet. Is there something about a lot of recombinants that supports“flu-like drift” I'm missing?
Thanks for a great post, Katelyn, helping us understand where the uncertainties lie (and why they are uncertain). It's fascinating and inspiring that there is so much work worldwide and that so much of it is being shared - which points out the urgent need for the public to understand how science works. QUESTION: Is there an evidence base for the statement "viruses evolve to become more transmissible but less pathological?" (Meaning it's not "in their interest" to kill their host) It seems that by the time the host transmits the virus, the virus "doesn't care" what happens to the host. If true, then it seems there wouldn't *necessarily* be selective pressure on pathogenicity
no, unfortunately that is a common misconception. viruses don’t mutate to become less severe. all they care about is surviving, so if it becomes more transmissible and just happens to be severe, then that’s what will spread because it’s working.
My mental model is that these first few variants are like shrapnel from an evolutionary explosion. Isn't Omicron thought to have branched off pretty early? In which case we're bound to see stuff keep turning up...until it doesn't, because there's some evidence of convergent evolution and the space of mathematically possible variants is much larger than the space of variants that can actually occur in nature (and thrive). Is that a fair assessment?
Super interesting that "there are really only two antigenic spaces or areas of vulnerability this could happen: a virus that is closer to Beta, or a virus that is closer to Delta."
Are there implications here that our vaccine induced cellular immunity would be somewhat effective going forward into this space?
i found this really interesting too. and in fact he and the NIH just started a study to assess whether current or future vaccines work not only currently but also in this space. unfortunately it will take a while to see the results
Great exposition! I take heart that this virus will reach an accommodation with us that is fairly predictable and manageable. It may not seem like it right now, but we really dodged a bullet with covid, it could have been far far, worse.
Three things are certain. Death, taxes, and more zoonotic pandemics. After we "tame" the coronaviruses I'm fearing the next may be a highly contagious orthopox virus with a long asymptomatic stage.
Yes. With the impingement of human activity in formerly wild lands, it all but certain we are going to have some more outbreaks. Something new popped up in Brazil last year
The current pandemic has us all thinking in terms of viral outbreaks. But we should keep in mind that some of the most horrible pandemics have been bacterial in origin such as V. Cholerae and Y. Pestis. Both of which are still out there unfortunately.
Not related to this post, but wondering if you would do a post on vaccines for children under 5? Moderna made a splash with their trial data and then there has been silence. What is going on?
Why do we want high transmissions and more contagion (eg. XE) when the evidence is piling up that there can be substantial side-effects from even mild and moderate COVID infections, and even those aren't fully understood yet? I want someone to explain this to me very clearly because I'm not digging what I'm seeing right now. This is going to have future health implications, especially if it's hitting all systems in a fairly slipshod manner (as preliminary studies seem to be suggesting).
"there are really only two antigenic spaces or areas of vulnerability this could happen: a virus that is closer to Beta, or a virus that is closer to Delta."
Is this because they are more likely to give rise to a more severe disease? Or is it something about the likelihood of these kinds of mutations occurring over a more Omicron like virus?
Not related to this post, but I wish you would put up a post talking up the post-exposure therapeutics, Paxlovid and the like. I have encountered dozens of people who do not know about this stuff in the past month, and most of them are people with college educations or graduate degrees, people who are vaxed, boosted and fairly well-informed. AND I'd say a third of them are 65+ or have a health problem that's a substantial risk factor.
I often read screeds by health professionals about how we need to get more people vaxed and boosted, improve ventilation in buildings, develop systems for evaluating current risk and adjusting precautions accordingly. All great points, BUT these same people don't say a word about Paxlovid, etc. I just don't understand it. Do they not realize how underutilized these treatments are? Are they afraid unvaccinated people will be even less likely to finally get vaxed if they know there are treatments that help high-risk people if they get infected? Are they all having a brain glitch?
Prevention is always preferable to treatment after becoming infected. THAT's why we want to get people vaxxed, improve air filtration/quality, evaluate risk and employ risk mitigation. Monoclonal antibodies were a Big Thing in Florida, despite the fact that DeSantis and his legion of surgeons general didn't understand that vaccination produced the same antibodies he wanted people be given , save as a preexposure method, they were more effective than if administere as an extract post-exposure.
Hey, are you going to reply? I posted a comment here on 4/12, you replied on 4/17, and I responded to your comment on the same day. My response ended with a question. It is probably evident from what I said that my views do not align perfectly with yours, but my response and question were perfectly civil. This is a discussion forum, not a place for you to post Expert Bulletins. How about answering?
I totally get it that prevention is preferable to treatment. I totally get it that the Big Monoclonal Thing in Florida is idiotic. You're preaching to the choir about that stuff. But here's the question: Now that there are post-exposure drugs that are highly effective for high-risk people, should we or shouldn't we make sure the public is aware of the availability of these drugs, so that those likely to benefit from these drugs get them? On the one hand, it sure would be a shame if somebody 65+ who is vaxed, boosted and cautious but in fragile health gets covid, does not know about Paxlovid and similar, and ends up hospitalized with severe illness. Paxloxvid would have reduced that person's chances of hospitalization and death by around 90%. On the other hand, it's infuriating to think that the existence of Paxlovid and the rest might increase the number of people who refuse vaccination on the grounds that "if I get it I'll just take Paxlovid."
Nobody knows how it would play out if these drugs were better publicized: Would the lives saved outweigh the downside? Sounds like you're inclined to think the downside is more significant than the upside -- lots of people will become less interested in vaccination, masking, etc. Is that right?
"Our model predicts that COVID-19 is likely to become the leading cause of death in the US under many scenarios. For example, for a hypothetical SARS-CoV-2 variant with an R0 of 5, an IFR of 1%, and a 12-month duration of natural immunity, approximately 700,000 US COVID-19 deaths could be expected per year if a vaccine preventing 90% of infections were administered to 70% of the population. We observe that despite a high degree of vaccine efficacy – 90% reduction in risk of infection and 90% reduction in risk of death given infection– the region in which US COVID-19 deaths under endemic conditions rival influenza deaths (12,000 – 52,000 per year, according to the CDC50) is small and would require a significant reduction in IFR."
One thing this model isn't taking into account is that we now have antiviral meds that are highly effective. These are drugs that are given early on after someone is diagnosed. Paxlovid, for instance, is 80%-90% effective in preventing hospitalization and death in those most likely to die (those age 65+, and the unvaccinated). People in those categories account for MOST of the covid deaths. I believe approx. 70% of those who have died so far are aged 65+, and a good number of the remaining 30% of deaths were in people who were younger but unvaxed. And there are more drugs for the infected in the works.
So far, the rapid antigen tests are working Just Fine, because the antigen content they're looking for isn't limited to just the Spike or Receptor Binding Domain. Where rapid Antigen tests are failing is there's no consistent mechanism to report and manage the results on a regional or national scale.
Katelyn, you really are more than a local epidemiologist. An "LE" wouldn't "call" with periodic valuable updates! Thank you.
Suggestion for a future post:
An update on your views of Long Covid.
What is the reasoning behind "we expect with high certainty a “flu-like drift” of SARS-CoV-2" ? It seems like everything you said (and I've read elsewhere) is that viral evolution hasn't fit any known models or patterns. Omicrons BA.1 and BA.2 are as different from each other as Alpha, Beta, Gamma, and Delta are from one another, so that isn't ladder like change yet. Is there something about a lot of recombinants that supports“flu-like drift” I'm missing?
Thanks for a great post, Katelyn, helping us understand where the uncertainties lie (and why they are uncertain). It's fascinating and inspiring that there is so much work worldwide and that so much of it is being shared - which points out the urgent need for the public to understand how science works. QUESTION: Is there an evidence base for the statement "viruses evolve to become more transmissible but less pathological?" (Meaning it's not "in their interest" to kill their host) It seems that by the time the host transmits the virus, the virus "doesn't care" what happens to the host. If true, then it seems there wouldn't *necessarily* be selective pressure on pathogenicity
no, unfortunately that is a common misconception. viruses don’t mutate to become less severe. all they care about is surviving, so if it becomes more transmissible and just happens to be severe, then that’s what will spread because it’s working.
My mental model is that these first few variants are like shrapnel from an evolutionary explosion. Isn't Omicron thought to have branched off pretty early? In which case we're bound to see stuff keep turning up...until it doesn't, because there's some evidence of convergent evolution and the space of mathematically possible variants is much larger than the space of variants that can actually occur in nature (and thrive). Is that a fair assessment?
Super interesting that "there are really only two antigenic spaces or areas of vulnerability this could happen: a virus that is closer to Beta, or a virus that is closer to Delta."
Are there implications here that our vaccine induced cellular immunity would be somewhat effective going forward into this space?
i found this really interesting too. and in fact he and the NIH just started a study to assess whether current or future vaccines work not only currently but also in this space. unfortunately it will take a while to see the results
Great exposition! I take heart that this virus will reach an accommodation with us that is fairly predictable and manageable. It may not seem like it right now, but we really dodged a bullet with covid, it could have been far far, worse.
Truth. While bad it could have been worse and our mRNA productive vaccine contributed to that lessening of a bad pandemic.
Don't forget all the people who volunteered their bodies for clinical trials - in some cases accepting placebos, or even challenge trials.
Three things are certain. Death, taxes, and more zoonotic pandemics. After we "tame" the coronaviruses I'm fearing the next may be a highly contagious orthopox virus with a long asymptomatic stage.
Yes. With the impingement of human activity in formerly wild lands, it all but certain we are going to have some more outbreaks. Something new popped up in Brazil last year
The current pandemic has us all thinking in terms of viral outbreaks. But we should keep in mind that some of the most horrible pandemics have been bacterial in origin such as V. Cholerae and Y. Pestis. Both of which are still out there unfortunately.
Not related to this post, but wondering if you would do a post on vaccines for children under 5? Moderna made a splash with their trial data and then there has been silence. What is going on?
Why do we want high transmissions and more contagion (eg. XE) when the evidence is piling up that there can be substantial side-effects from even mild and moderate COVID infections, and even those aren't fully understood yet? I want someone to explain this to me very clearly because I'm not digging what I'm seeing right now. This is going to have future health implications, especially if it's hitting all systems in a fairly slipshod manner (as preliminary studies seem to be suggesting).
"there are really only two antigenic spaces or areas of vulnerability this could happen: a virus that is closer to Beta, or a virus that is closer to Delta."
Is this because they are more likely to give rise to a more severe disease? Or is it something about the likelihood of these kinds of mutations occurring over a more Omicron like virus?
Not related to this post, but I wish you would put up a post talking up the post-exposure therapeutics, Paxlovid and the like. I have encountered dozens of people who do not know about this stuff in the past month, and most of them are people with college educations or graduate degrees, people who are vaxed, boosted and fairly well-informed. AND I'd say a third of them are 65+ or have a health problem that's a substantial risk factor.
I often read screeds by health professionals about how we need to get more people vaxed and boosted, improve ventilation in buildings, develop systems for evaluating current risk and adjusting precautions accordingly. All great points, BUT these same people don't say a word about Paxlovid, etc. I just don't understand it. Do they not realize how underutilized these treatments are? Are they afraid unvaccinated people will be even less likely to finally get vaxed if they know there are treatments that help high-risk people if they get infected? Are they all having a brain glitch?
Prevention is always preferable to treatment after becoming infected. THAT's why we want to get people vaxxed, improve air filtration/quality, evaluate risk and employ risk mitigation. Monoclonal antibodies were a Big Thing in Florida, despite the fact that DeSantis and his legion of surgeons general didn't understand that vaccination produced the same antibodies he wanted people be given , save as a preexposure method, they were more effective than if administere as an extract post-exposure.
Hey, are you going to reply? I posted a comment here on 4/12, you replied on 4/17, and I responded to your comment on the same day. My response ended with a question. It is probably evident from what I said that my views do not align perfectly with yours, but my response and question were perfectly civil. This is a discussion forum, not a place for you to post Expert Bulletins. How about answering?
I totally get it that prevention is preferable to treatment. I totally get it that the Big Monoclonal Thing in Florida is idiotic. You're preaching to the choir about that stuff. But here's the question: Now that there are post-exposure drugs that are highly effective for high-risk people, should we or shouldn't we make sure the public is aware of the availability of these drugs, so that those likely to benefit from these drugs get them? On the one hand, it sure would be a shame if somebody 65+ who is vaxed, boosted and cautious but in fragile health gets covid, does not know about Paxlovid and similar, and ends up hospitalized with severe illness. Paxloxvid would have reduced that person's chances of hospitalization and death by around 90%. On the other hand, it's infuriating to think that the existence of Paxlovid and the rest might increase the number of people who refuse vaccination on the grounds that "if I get it I'll just take Paxlovid."
Nobody knows how it would play out if these drugs were better publicized: Would the lives saved outweigh the downside? Sounds like you're inclined to think the downside is more significant than the upside -- lots of people will become less interested in vaccination, masking, etc. Is that right?
Hi, I just read this article, and it's pretty grim. https://www.medrxiv.org/content/10.1101/2022.03.29.22273146v1.full-text The following paragraph really got my attention:
"Our model predicts that COVID-19 is likely to become the leading cause of death in the US under many scenarios. For example, for a hypothetical SARS-CoV-2 variant with an R0 of 5, an IFR of 1%, and a 12-month duration of natural immunity, approximately 700,000 US COVID-19 deaths could be expected per year if a vaccine preventing 90% of infections were administered to 70% of the population. We observe that despite a high degree of vaccine efficacy – 90% reduction in risk of infection and 90% reduction in risk of death given infection– the region in which US COVID-19 deaths under endemic conditions rival influenza deaths (12,000 – 52,000 per year, according to the CDC50) is small and would require a significant reduction in IFR."
Isn't the R(0) of BA.2 10-14?
Yes.
One thing this model isn't taking into account is that we now have antiviral meds that are highly effective. These are drugs that are given early on after someone is diagnosed. Paxlovid, for instance, is 80%-90% effective in preventing hospitalization and death in those most likely to die (those age 65+, and the unvaccinated). People in those categories account for MOST of the covid deaths. I believe approx. 70% of those who have died so far are aged 65+, and a good number of the remaining 30% of deaths were in people who were younger but unvaxed. And there are more drugs for the infected in the works.
This thing is keeping all of us guessing ... what a strange disease it's been.
Katelyn, one point to ponder: The coronaviruses are not the influenza virus. Different families, different mutation paths.
How are the rapid antigen tests holding up under omicron, BA.2, etc.? I've heard rumors they're giving a lot of false negatives.
So far, the rapid antigen tests are working Just Fine, because the antigen content they're looking for isn't limited to just the Spike or Receptor Binding Domain. Where rapid Antigen tests are failing is there's no consistent mechanism to report and manage the results on a regional or national scale.
Brilliant information - thank you!
Thank you for this post!