I know this is likely in response to the viral, scary article being passed around widely. I always appreciate your sane and comprehensive write-ups! Couple of curious questions ...
1) If re-infections are rare -- maybe at most ~27% of infections -- shouldn't we be running out of folks who've never been infected before? For example, we know that the number of people who've ever been infected in those under 18 in the US as of Feb 2022 was around 75% IIRC. Is it still possible that today (or very recently) 75% of new cases in those under 18 are from that incredibly shrinking 25% who had never been infected?
I know anecdotally, I don't have many friends who've still never caught COVID.
Methodologically, if we're not great at counting actual cases (I see some reputable people apply a 5x multiplier to current case counts in the US to estimate actual cases), wouldn't it also stand to reason that we've even more terrible at counting re-infections? It would be like lighting striking twice. I guess my question is whether or not we're undercounting cases and then by extension (squaring the probability), very much undercounting re-infections.
I feel like if reinfections were actually as rare as these numbers suggest, we should be running out of new folks earlier this year.
2) Part of the public horror about the danger of re-infection is that it goes against the public's prior understanding of the risks. Many folks believed it was "one and done" and there was some value to simply "getting it over with." Likewise, if there was some rare change of a re-infection, it wasn't anything to worry about because someone already had immunity.
I think the reason that article (as careless as it might have been with language and hyperbolic) went viral was because it was making a few key points. 1) It isn't one and done. The virus mutates more quickly than expected. Reinfections can definitely happen and they can even happen on a surprisingly quick timeline. 2) Re-infections pose some additional health risk. Whether that risk is the same as the initial infection or to a lesser degree, there is *some* additional risk associated with getting re-infected. Which leads to 3) Unmitigated transmission is a problem (both for individuals and society) and no matter your prior infection history, you should continue taking active steps to minimize your total number of infections. Even if you've had it, you should keep from getting it again. It's not necessarily "no covid" (almost impossible to avoid), but our philosophy needs to be "low covid" (as few infections as possible).
The well-intentioned "take-downs" I see of that article seem to miss the gist behind why it went viral in the first place.
How concerned should we be about cumulative risk (longer term) of multiple infections? I think this is a key point. It’s been such a struggle to get the general population to see that taking reasonable precautions to avoid infection and reinfection as we learn more about a novel virus is a reasonable goal for overall health at any age.
I wonder if we have any suggestive evidence from other viral infections - for example, it seems like colds (some of which are due coronavirus varieties) don't necessarily get worse with each cold (unless the person has underlying health problems). Is this relevant? Likewise, I've read in vaccine-skeptical blogs about the concern that repeated vaccination drains or somehow impairs "the immune system" (deliberately in quotes)
Is there any talk about allowing 2nd boosters for a younger age group? I know many people in their 30's and 40's who want a second booster but aren't eligible. Those who have been extremely careful are now getting Covid with dropping their guard briefly. As so few are getting even the initial booster, shouldn't these be available?
I understand the math and science behind it, but as other meds are often prescribed that later prove to have little or just minimal effect or at a low level of effectiveness, I say let people try. Look at the results for the youngest children, the vaccine isn't as effective as it is for adults, but if I had a child that age, I'd have them vaccinated in a flash. I don't know if Moderna or Pfizer will take the time to do another study on boosting younger people.
In general terms, and especially with the immune system, "letting people try" isn't something we like to do. That was the original logic behind Pfizer's attempt to use the lowest possible dose for kids; what they thought was a lower, safer dose didn't fully meet the study criteria for success.
So great to open the mail in the morning out here on the west coast and see one of your reports! Having long covid from a moderate (with fever) B.1 infection in spring 2020, I've noticed a strange periodicity over a two year period of symptoms waxing then waning then waxing again. Not a reinfection process so much as a resident living in an uneasy equilibrium with the immune system. Can the virus have harbors in the body where it is occult to the immune system and periodically re-erupt? My experience is that over 26 months the symptoms have been steadily weakening and at the present rate may be entirely gone in a year.
Being obsessive compulsive is sometimes a blessing! As is being a quant. I compulsively journaled all my symptoms for the 2020 - 2022 period, with strength and duration quantifiers and a picture of polyrhythms of symptom types with steady decreasing intensity emerges. Conclusion was that this was not a case of reinfections or chronic inflammatory response to past but now vanished virus, but some other phenomenon. But what?
Probably I'm just a statistical outlier; be hard to draw conclusions from a sample set with just one member!! The true picture will emerge in s year or so, no doubt. 🙂
Thank you as always- Can you revisit pediatric risk and outcomes? I have read that the newest variants are more contagious for young children and as a preschool director, in line with how most of the world is moving on, I’m trying to review and relax some long standing more cautious protocols but I want it to be well-reasoned.
Katelyn - I'm not very science-savvy, but I recently ran across a couple new discoveries on long COVID I thought you might find interesting. Actually, I assume you're already aware of them, but just in case!
First, a new MRI technique that found an "abnormality in the exchange of oxygen across the alveolar membrane that depresses transition of oxygen into red blood cells." Evidence of it being a vascular disease that messes with out circulatory system, and might explain some of the long COVID respiratory symptoms. https://www.sciencealert.com/new-imaging-techniques-starkly-reveals-what-long-covid-lungs-can-look-like
Second, an NIH study that found it was "the people's own antibodies that attacked the cells lining the brain's blood vessels, causing inflammation and damage. This discovery could explain why some people have lingering effects from infection including headache, fatigue, loss of taste and smell, and inability to sleep as well as "brain fog" – and may also help devise new treatments for long COVID." https://www.sciencealert.com/where-does-brain-fog-come-from-new-evidence-could-solve-the-mystery
I feel like this is a silly/simplistic question, but I wonder about it whenever I see information showing less severe disease and less deaths as time goes on... is any of this explained by the fact that so many high risk people died from primary infection? It stands to reason that those who survived once would be at less risk for severe disease if they were to be reinfected. Over time, sadly, there are less vulnerable people to infect, so on a population level the risk of severe disease and death is lower, but if you are (or love) a vulnerable person, is the risk really any lower?
Not a silly question at all! This is called survivorship bias in epidemiology. And, actually, was another limitation to that VA study (I didn't dive into it). So, yes, reinfections are naturally only among those that made it past this first "selection process".
Note that hybrid immunity (prior infection plus vaccination) tends to protect better in all aspects than infection or full immunization alone. And note I didn't use the term "up to date" in that statement.
I understand. Ironically I was just reading the WashPo coronavirus updates discussing this. This was actually a response to a question about why boosters aren’t automatically available every 4 months. This section is at the end of the article. “Some U.S. officials have signaled that more people should have access to another booster. Anthony S. Fauci, the government’s top-infectious disease expert, said he's “leaning toward flexibility” for adults younger than 50 who got their last booster many months ago, and whose immunity is waning.” Gee, great minds…lol.
"Safety doesn’t appear to be an issue,” Fauci told The Post, listing other considerations too, like expiring supply. “We got a lot of doses, if we don’t get them into people soon, they’re going to be wasted.”
Having not had covid, but living with asthma and multiple sclerosis I'm 100% certain we are going to see a rise in autoimmune diseases in the coming years. It's horrifying.
Excellent analysis. Really appreciate all you do. Would love to hear your latest thoughts and the research on adult boosters — especially in light of new variants. If one has had the two regular doses and a booster, should one try to get a second booster given the state of the world?
The VA study was much more useful to epidemiologists and ID docs than to the public because of the way they compared cohorts. It does still highlight that there is an increased risk for reinfection... and for serial reinfection, however, that clinicians need to be able to advise about. Anecdotally, my wife and I had our first infection in July, 2020 and recovered. We were reinfected in early February 2022. I recovered fine, but she's exhibiting signs of long-COVID. We were, in February, fully up to date. Timing suggests BA.1.
I'll also offer that BA.4/5 are closer to a new, novel coronavirus in their immune-evasion and the fact that they really don't produce antibodies against ancestral variants.
She's four months into the long-COVID track. Exhibiting signs of POTS, an autonomic postural tachycardia, which has some differences in post-COVID from the more generic POTS. Heat intolerant, and tires easily. No real signs of resolution so far.
This is an interesting article but rather niche-focused. In general, it's thought that the vascular effects of microclot evolution are derived from a variety of sources. I suspect the best take-home from this report (which I'm re-reading for additional content) is the use of a triple-anticoagulant therapy. A competent 3-drug cocktail should address misdirected fibrenogen constructs, increased platelet activation and endothelial exacerbations that can lead to "normal" clot cascades.
It's certainly possible this paper will become the seminal element in treating both acute and long COVID but it'll take time and other research groups confirming results.
Teasing out the mechanisms of COVID as a vascular disease are starting to be seen in the literature. That said, I've argued for well over 18 months that COVID's a vascular illness. If we're looking at an anomalous fibrinogen mechanism in thrombocytopenic yet hypercoagulable patients, that's a reasonable explanation. But 2 studies on preprint servers don't constitute a final answer to this question.
I'd missed the first article although it's pretty general in nature. I'm not sure I completely concur with Goodwin. I suspect she has cause and effect reversed. Infiltration of endothelium was found early on. There was evidence, as well, that endothelial changes and endovascular changes in the alveoli and capillary beds changed the nature of the exudate filling the alveoli and making it difficult to 'recruit' alveoli using conventional high-pressure, high-PEEP volume ventilation. This was contributory to the loss of so many patients early on who were intubated and mechanically ventilated based on earlier ARDS experience and respiratory failure criteria.
I know this is likely in response to the viral, scary article being passed around widely. I always appreciate your sane and comprehensive write-ups! Couple of curious questions ...
1) If re-infections are rare -- maybe at most ~27% of infections -- shouldn't we be running out of folks who've never been infected before? For example, we know that the number of people who've ever been infected in those under 18 in the US as of Feb 2022 was around 75% IIRC. Is it still possible that today (or very recently) 75% of new cases in those under 18 are from that incredibly shrinking 25% who had never been infected?
I know anecdotally, I don't have many friends who've still never caught COVID.
Methodologically, if we're not great at counting actual cases (I see some reputable people apply a 5x multiplier to current case counts in the US to estimate actual cases), wouldn't it also stand to reason that we've even more terrible at counting re-infections? It would be like lighting striking twice. I guess my question is whether or not we're undercounting cases and then by extension (squaring the probability), very much undercounting re-infections.
I feel like if reinfections were actually as rare as these numbers suggest, we should be running out of new folks earlier this year.
2) Part of the public horror about the danger of re-infection is that it goes against the public's prior understanding of the risks. Many folks believed it was "one and done" and there was some value to simply "getting it over with." Likewise, if there was some rare change of a re-infection, it wasn't anything to worry about because someone already had immunity.
I think the reason that article (as careless as it might have been with language and hyperbolic) went viral was because it was making a few key points. 1) It isn't one and done. The virus mutates more quickly than expected. Reinfections can definitely happen and they can even happen on a surprisingly quick timeline. 2) Re-infections pose some additional health risk. Whether that risk is the same as the initial infection or to a lesser degree, there is *some* additional risk associated with getting re-infected. Which leads to 3) Unmitigated transmission is a problem (both for individuals and society) and no matter your prior infection history, you should continue taking active steps to minimize your total number of infections. Even if you've had it, you should keep from getting it again. It's not necessarily "no covid" (almost impossible to avoid), but our philosophy needs to be "low covid" (as few infections as possible).
The well-intentioned "take-downs" I see of that article seem to miss the gist behind why it went viral in the first place.
How concerned should we be about cumulative risk (longer term) of multiple infections? I think this is a key point. It’s been such a struggle to get the general population to see that taking reasonable precautions to avoid infection and reinfection as we learn more about a novel virus is a reasonable goal for overall health at any age.
I wonder if we have any suggestive evidence from other viral infections - for example, it seems like colds (some of which are due coronavirus varieties) don't necessarily get worse with each cold (unless the person has underlying health problems). Is this relevant? Likewise, I've read in vaccine-skeptical blogs about the concern that repeated vaccination drains or somehow impairs "the immune system" (deliberately in quotes)
I read a very preliminary study that it may increase the risk of Long Covid, but who knows?
the data are sparse, but the current leaning is that BA.4/5 are somewhat less likely to product long-COVID.
Is there any talk about allowing 2nd boosters for a younger age group? I know many people in their 30's and 40's who want a second booster but aren't eligible. Those who have been extremely careful are now getting Covid with dropping their guard briefly. As so few are getting even the initial booster, shouldn't these be available?
I understand the math and science behind it, but as other meds are often prescribed that later prove to have little or just minimal effect or at a low level of effectiveness, I say let people try. Look at the results for the youngest children, the vaccine isn't as effective as it is for adults, but if I had a child that age, I'd have them vaccinated in a flash. I don't know if Moderna or Pfizer will take the time to do another study on boosting younger people.
In general terms, and especially with the immune system, "letting people try" isn't something we like to do. That was the original logic behind Pfizer's attempt to use the lowest possible dose for kids; what they thought was a lower, safer dose didn't fully meet the study criteria for success.
Thanks, thanks! Not just for the information but how you write clearly enough for non-science folks to understand!
So great to open the mail in the morning out here on the west coast and see one of your reports! Having long covid from a moderate (with fever) B.1 infection in spring 2020, I've noticed a strange periodicity over a two year period of symptoms waxing then waning then waxing again. Not a reinfection process so much as a resident living in an uneasy equilibrium with the immune system. Can the virus have harbors in the body where it is occult to the immune system and periodically re-erupt? My experience is that over 26 months the symptoms have been steadily weakening and at the present rate may be entirely gone in a year.
Being obsessive compulsive is sometimes a blessing! As is being a quant. I compulsively journaled all my symptoms for the 2020 - 2022 period, with strength and duration quantifiers and a picture of polyrhythms of symptom types with steady decreasing intensity emerges. Conclusion was that this was not a case of reinfections or chronic inflammatory response to past but now vanished virus, but some other phenomenon. But what?
Probably I'm just a statistical outlier; be hard to draw conclusions from a sample set with just one member!! The true picture will emerge in s year or so, no doubt. 🙂
Thank you as always- Can you revisit pediatric risk and outcomes? I have read that the newest variants are more contagious for young children and as a preschool director, in line with how most of the world is moving on, I’m trying to review and relax some long standing more cautious protocols but I want it to be well-reasoned.
Katelyn - I'm not very science-savvy, but I recently ran across a couple new discoveries on long COVID I thought you might find interesting. Actually, I assume you're already aware of them, but just in case!
First, a new MRI technique that found an "abnormality in the exchange of oxygen across the alveolar membrane that depresses transition of oxygen into red blood cells." Evidence of it being a vascular disease that messes with out circulatory system, and might explain some of the long COVID respiratory symptoms. https://www.sciencealert.com/new-imaging-techniques-starkly-reveals-what-long-covid-lungs-can-look-like
Second, an NIH study that found it was "the people's own antibodies that attacked the cells lining the brain's blood vessels, causing inflammation and damage. This discovery could explain why some people have lingering effects from infection including headache, fatigue, loss of taste and smell, and inability to sleep as well as "brain fog" – and may also help devise new treatments for long COVID." https://www.sciencealert.com/where-does-brain-fog-come-from-new-evidence-could-solve-the-mystery
I feel like this is a silly/simplistic question, but I wonder about it whenever I see information showing less severe disease and less deaths as time goes on... is any of this explained by the fact that so many high risk people died from primary infection? It stands to reason that those who survived once would be at less risk for severe disease if they were to be reinfected. Over time, sadly, there are less vulnerable people to infect, so on a population level the risk of severe disease and death is lower, but if you are (or love) a vulnerable person, is the risk really any lower?
Not a silly question at all! This is called survivorship bias in epidemiology. And, actually, was another limitation to that VA study (I didn't dive into it). So, yes, reinfections are naturally only among those that made it past this first "selection process".
This study from South Africa shows that vax + Omicron BA1 infection has antibodies holding up against BA5. But unvax + BA1 infection leaves little protection against reinfection. Seems to hold up with real world wave results. https://secureservercdn.net/166.62.108.196/1mx.c5c.myftpupload.com/wp-content/uploads/2022/04/MEDRXIV-2022-274477v1-Sigal.pdf
Note that hybrid immunity (prior infection plus vaccination) tends to protect better in all aspects than infection or full immunization alone. And note I didn't use the term "up to date" in that statement.
Fantastic article. Grateful for how you break down complex and varied data from so many sources!
I understand. Ironically I was just reading the WashPo coronavirus updates discussing this. This was actually a response to a question about why boosters aren’t automatically available every 4 months. This section is at the end of the article. “Some U.S. officials have signaled that more people should have access to another booster. Anthony S. Fauci, the government’s top-infectious disease expert, said he's “leaning toward flexibility” for adults younger than 50 who got their last booster many months ago, and whose immunity is waning.” Gee, great minds…lol.
"Safety doesn’t appear to be an issue,” Fauci told The Post, listing other considerations too, like expiring supply. “We got a lot of doses, if we don’t get them into people soon, they’re going to be wasted.”
Having not had covid, but living with asthma and multiple sclerosis I'm 100% certain we are going to see a rise in autoimmune diseases in the coming years. It's horrifying.
Could what appears to be a more severe reinfection be a prime/boost effect?
Excellent analysis. Really appreciate all you do. Would love to hear your latest thoughts and the research on adult boosters — especially in light of new variants. If one has had the two regular doses and a booster, should one try to get a second booster given the state of the world?
My husband and I (both in our mid-50s) got our second boosters as soon as they were available.
Great summary. Again. Thanks.
The VA study was much more useful to epidemiologists and ID docs than to the public because of the way they compared cohorts. It does still highlight that there is an increased risk for reinfection... and for serial reinfection, however, that clinicians need to be able to advise about. Anecdotally, my wife and I had our first infection in July, 2020 and recovered. We were reinfected in early February 2022. I recovered fine, but she's exhibiting signs of long-COVID. We were, in February, fully up to date. Timing suggests BA.1.
I'll also offer that BA.4/5 are closer to a new, novel coronavirus in their immune-evasion and the fact that they really don't produce antibodies against ancestral variants.
Would you feel comfortable sharing if her long-COVID symptoms are improving? Are they/were they severe? Hoping she is on her way back to normal.
She's four months into the long-COVID track. Exhibiting signs of POTS, an autonomic postural tachycardia, which has some differences in post-COVID from the more generic POTS. Heat intolerant, and tires easily. No real signs of resolution so far.
I'm very sorry to hear this. Hoping time (and not too much of it) resolves these issues.
Your analysis is for respiratory infections, but what about the data that SARS-CoV-2 is a vascular disease?
https://mobile.twitter.com/drclairetaylor/status/1534659652901822465?s=20&t=jHAgOcRy_la0UH_Rt3-nFA
Not according to this paper. https://portlandpress.com/biochemj/article/479/4/537/230829/A-central-role-for-amyloid-fibrin-microclots-in
This is an interesting article but rather niche-focused. In general, it's thought that the vascular effects of microclot evolution are derived from a variety of sources. I suspect the best take-home from this report (which I'm re-reading for additional content) is the use of a triple-anticoagulant therapy. A competent 3-drug cocktail should address misdirected fibrenogen constructs, increased platelet activation and endothelial exacerbations that can lead to "normal" clot cascades.
It's certainly possible this paper will become the seminal element in treating both acute and long COVID but it'll take time and other research groups confirming results.
Or this pre-print: https://www.researchsquare.com/article/rs-1727226/v1
Teasing out the mechanisms of COVID as a vascular disease are starting to be seen in the literature. That said, I've argued for well over 18 months that COVID's a vascular illness. If we're looking at an anomalous fibrinogen mechanism in thrombocytopenic yet hypercoagulable patients, that's a reasonable explanation. But 2 studies on preprint servers don't constitute a final answer to this question.
I'd missed the first article although it's pretty general in nature. I'm not sure I completely concur with Goodwin. I suspect she has cause and effect reversed. Infiltration of endothelium was found early on. There was evidence, as well, that endothelial changes and endovascular changes in the alveoli and capillary beds changed the nature of the exudate filling the alveoli and making it difficult to 'recruit' alveoli using conventional high-pressure, high-PEEP volume ventilation. This was contributory to the loss of so many patients early on who were intubated and mechanically ventilated based on earlier ARDS experience and respiratory failure criteria.