Dr. Jetelina, this is a MASTERPIECE of information-packed clear writing. You are a public health, public-facing information rock star. Thank you so much.
This really is a great compilation of all the stuff I’ve been reading, but all in one place. It’s been a flurry of studies lately! I think Eric Topol would say the same, as he dropped a related post full of good stuff.
I would add complement system activation and dysregulation to the immune system dysfunction bucket:
Metformin is mentioned here as potentially helpful, and has previously been shown to have protective effects with respect to mitochondria, another casualty among the subsets of long Covid.
It seems like we need to start formally carving long Covid into distinct categories defined not only by symptoms but also by evolving biomarkers. Much as cancers are now classified by TNM, histological, and biomarker profiles. Each is a slightly different disease within their umbrella, and therefore can present different targets for treatment. It’s one of the promises of individualized immunotherapies for cancer based on each unique phenotype and genotype… at least that’s how the future contours might look to me from primary care.
Yes, “all in one place,” along with well-organized, layperson-friendly language, are keys to why I thought this post so enormously helpful. BTW, when I saw Dr. Topol’s post, I thought much the same as you. This particular post was mostly way over my head, but his ability to round up and synthesize the state of the research, and so quickly, always amazes me.
Thanks Katelyn! Glad you are in contact with Betsy and Miles at The Sick Times. You and Betsy are my go to people when it comes to COVID. Been following both since close to the start of the pandemic.
Thank you, Dr. Jetelina, for this comprehensive overview and for the recommendation to subscribe to “The Sick Times” newsletter. I found them on Twitter/X and they did a great job live tweeting about the Senate Committee hearing on Long Covid today. The committee heard from people with Long Covid (and a parent of a teenager with Long Covid), as well as experts in the field. It was a promising start to addressing this important topic at the national level, and the bipartisan agreement and civil tone of discussion gives me hope for some meaningful governmental action on this topic.
Thanks so much for explaining the latest research findings! It's much appreciated.
I have a question about California's updated isolation guidance for COVID. The guidelines are more lax, with reduced isolation times. I'm very worried this will lead to increased spread of COVID. Also, I'm concerned that sick people won't have enough time to rest and recover at home.
Thank you for these updates. In addition, it would be really helpful if you could revisit the kind of information you gave in your past post that was comparing risks of long covid and the level of debilitation with other things we commonly take risks for (e.g., your post comparing it to long-term effects of car accidents, dog bites, etc.). Have any of those rates changed since that post? If not, that'd be great to know, too.
Also, could you also do a Research Round-up about long-term risks that don't fall under the "long covid" category? Like increased risk of diabetes for children, increased blood clots?, etc.? I feel like these risks are discussed here and there, but it'd be great to have a comprehensive understanding of what we believe are the various multi-systemic impacts at this point.
Yes, if someone did such a risk calculation analysis, coupled with wastewater levels, it would be very helpful. If there was a 3 % chance of serious injury each time one got behind the wheel or on a plane, I'm sure many people would stop driving and flying.
As you pointed out, the term long covid (PASC) is an broad umbrella with many population subsets. This is not the only pathogen that can have long sequelae, Flu and Lyme for example. Hopefully research will help provide clues and treatments for a number of conditions like CFS and A one size fit all is not likely to work here. I did come across an interesting pilot trial of three people that receive treatment with casirivimab/imdevimab (Regeneron), a mABS that is no longer authorized. This was rendered ineffective by Delta/Omicron but it was suggested it may help with those affected prior to this. https://www.sciencedirect.com/science/article/pii/S073567572300534X
Gut microbiome may play a big role as well. A rather liberal use of antibiotics prescribed for covid didn't help here.
I will limit my comments to the purported reduction in risk of long covid among adults...
In your article you cite the Swedish study, Lundburg-Morris, et al, in the British Medical Journal. While you have accurately summarized the authors’ findings you have not put these results into context or pointed out the serious limitations of this singular study.
1) Though this large study found long Covid risk reduction amongst the vaccinated cohort that was significant, the risk of long Covid itself was very low in both the vaccinated and unvaccinated; vaccination offered about a 1% reduction in long-covid. This means that if you choose to vaccinate, there is a 1 in 100 chance that you will derive benefit with regard to this end point.
2) It is well known that the risk of long covid is directly correlated with the severity of infection. In this study there was a large imbalance between the two groups: 60.2% of persons of unvaccinated infections were infected with the alpha variant compared to the vaccinated where only 3.5% of them suffered infection with alpha. The opposite is true with regard to Omicron, a less severe variant: Nearly 75% of the infections in the vaccinated occurred with Omicron compared to only 12.4% in the unvaccinated. The heterogeneity between the two cohorts was not mentioned by the authors but impacts the significance of their findings.
3) People who vaccinated within 28 days of getting Covid were excluded from the study. This is an arbitrary window of time and by doing so nearly 60 thousand of a total of about 360 thousand vaccinated individuals were not part of the analysis. The authors are free to do this, of course, but given that they chose the cut off time arbitrarily, they should have followed up on them with regard to the primary outcome, i.e. long Covid. This would have been the appropriate approach to providing transparency. In other words, how do we know that a lot of those recently vaccinated folks didn’t develop long Covid? This could have completely upended the vaccine effectiveness calculation.
4) A different study (see below) which looked at the same outcome, long Covid, demonstrated exactly the opposite: the primary series INCREASED the risk of long-Covid by 130% over remaining unvaccinated. In this study, both cohorts were matched with regard to the infectious strain. This is actually not so surprising. Antibody-dependent Enhancement (ADE) is a known phenomenon, especially with regard to the mRNA products. I would appreciate your commentary on this study.
Anecdotally, and as a Biopharma researcher I realize anecdotes aren't data, my mother's college roommate said her Long COVID got much better after she got her booster shot in Fall 2023.
Thank you for this excellent LC (aka, PCC) Research Roundup. You once again manage to provide the exact information/insight I want, in the form that I want it.
I was very worried about long covid, because I have a hyperactive immune system, ‘long’ Epstein Barre, and Hashimoto’s. I finally had covid, took paxlovid, tested positive for 24 days with one negative day in the middle. For three weeks after testing negative again, I was exhausted all the time. I went to my integrative medicine MD and she recommended a three week, once weekly, course of IV NAC. It was amazing. Definite and significant improvements in how I felt and how quickly I was getting better after the first two treatments. Here is a link to one study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390689/ Of course, it was not cheap ($450 a treatment) and not covered by insurance, but so worth it.
I encourage folks with long covid to read Nicole Sachs and read about TMS/MBS and the brain-body connection. Many, many people have found their PASC symptoms go away once their nervous system moves from fight or flight to rest and repair (even things like ME/CFS, POTS, IBS, etc). Dan Buglio, Howard Schubiner, and Alan Gordon are other great places to start to learn about the science behind mind-body conditions.
One of the witnesses at the Senate hearing on Long COVID today made an important point about brain-body issues. She said in addition to brain-body issues, there are body-brain issues. A hallmark of Long COVID is neuro-inflammation, which is known to have damaging mental health effects. The upstream biological drivers have to be addressed first.
Thank you for keeping us up to date! I'm still trying to wrap my head around risk assessment and what can be done to avoid getting LC other than simply praying that the "Russian Roulette" of covid doesn't have a bullet with my name on it. I'm getting the latest boosters, still limiting social interactions during surges, eating outdoors, and masking in most public indoor spaces. Started using Enovid too, but its efficacy is not proven, so it's more of a placebo effect thing.
It's not a binary question. IIRC the first vaccines prevented up to 60% of infections by variants up to Delta in healthier and/or younger cohorts. Protection was substantially less in older cohorts with comorbidities.
Here's a reference for a more recent meta analysis that suggests the first vaccines were only about 20% effective in preventing infection against the Omicron family (https://www.mdpi.com/2076-393X/11/2/224)
This is a good question. I admit I haven't paid attention to the *type* of vaccine in these studies. Given mRNA and Novavax reduce infections (in short term) and reduce viral load, I would assume no meaningful difference in long Covid
Thank you, Dr. Jetelina. One other question about the two types of vaccines –why the recommendation for mRNA boosters but not the protein (Novavax) vaccine, as both reduce infection and viral load "in the short term"?
I'd love for you torevied Dr. Seheult's Medcram session on "Photobiomodulation for Long Covid". Interesting review from 4 months ago looking at near-infrared light therapy. https://www.youtube.com/watch?v=lLDYNoIVLmk
Very different from anything I learned in Med School!
Dr. Jetelina, this is a MASTERPIECE of information-packed clear writing. You are a public health, public-facing information rock star. Thank you so much.
100% - I just shared today's post with many people, telling them it's a "must read"
This really is a great compilation of all the stuff I’ve been reading, but all in one place. It’s been a flurry of studies lately! I think Eric Topol would say the same, as he dropped a related post full of good stuff.
I would add complement system activation and dysregulation to the immune system dysfunction bucket:
https://www.science.org/doi/10.1126/science.adg7942
Metformin is mentioned here as potentially helpful, and has previously been shown to have protective effects with respect to mitochondria, another casualty among the subsets of long Covid.
It seems like we need to start formally carving long Covid into distinct categories defined not only by symptoms but also by evolving biomarkers. Much as cancers are now classified by TNM, histological, and biomarker profiles. Each is a slightly different disease within their umbrella, and therefore can present different targets for treatment. It’s one of the promises of individualized immunotherapies for cancer based on each unique phenotype and genotype… at least that’s how the future contours might look to me from primary care.
Yes, “all in one place,” along with well-organized, layperson-friendly language, are keys to why I thought this post so enormously helpful. BTW, when I saw Dr. Topol’s post, I thought much the same as you. This particular post was mostly way over my head, but his ability to round up and synthesize the state of the research, and so quickly, always amazes me.
Thanks Katelyn! Glad you are in contact with Betsy and Miles at The Sick Times. You and Betsy are my go to people when it comes to COVID. Been following both since close to the start of the pandemic.
She's been great throughout the pandemic. I love her data-driven style.
Thank you, Dr. Jetelina, for this comprehensive overview and for the recommendation to subscribe to “The Sick Times” newsletter. I found them on Twitter/X and they did a great job live tweeting about the Senate Committee hearing on Long Covid today. The committee heard from people with Long Covid (and a parent of a teenager with Long Covid), as well as experts in the field. It was a promising start to addressing this important topic at the national level, and the bipartisan agreement and civil tone of discussion gives me hope for some meaningful governmental action on this topic.
For those who want to see the recorded committee meeting, it can be accessed here: https://www.help.senate.gov/hearings/addressing-long-covid-advancing-research-and-improving-patient-care
Thanks so much for explaining the latest research findings! It's much appreciated.
I have a question about California's updated isolation guidance for COVID. The guidelines are more lax, with reduced isolation times. I'm very worried this will lead to increased spread of COVID. Also, I'm concerned that sick people won't have enough time to rest and recover at home.
https://www.kpbs.org/news/health/2024/01/17/new-ca-covid-guidance-people-can-go-to-school-work-if-asymptomatic
What are your thoughts on this?
Thank you for these updates. In addition, it would be really helpful if you could revisit the kind of information you gave in your past post that was comparing risks of long covid and the level of debilitation with other things we commonly take risks for (e.g., your post comparing it to long-term effects of car accidents, dog bites, etc.). Have any of those rates changed since that post? If not, that'd be great to know, too.
Also, could you also do a Research Round-up about long-term risks that don't fall under the "long covid" category? Like increased risk of diabetes for children, increased blood clots?, etc.? I feel like these risks are discussed here and there, but it'd be great to have a comprehensive understanding of what we believe are the various multi-systemic impacts at this point.
Thank you so much!
Yes, if someone did such a risk calculation analysis, coupled with wastewater levels, it would be very helpful. If there was a 3 % chance of serious injury each time one got behind the wheel or on a plane, I'm sure many people would stop driving and flying.
As you pointed out, the term long covid (PASC) is an broad umbrella with many population subsets. This is not the only pathogen that can have long sequelae, Flu and Lyme for example. Hopefully research will help provide clues and treatments for a number of conditions like CFS and A one size fit all is not likely to work here. I did come across an interesting pilot trial of three people that receive treatment with casirivimab/imdevimab (Regeneron), a mABS that is no longer authorized. This was rendered ineffective by Delta/Omicron but it was suggested it may help with those affected prior to this. https://www.sciencedirect.com/science/article/pii/S073567572300534X
Gut microbiome may play a big role as well. A rather liberal use of antibiotics prescribed for covid didn't help here.
One day at a time.
I will limit my comments to the purported reduction in risk of long covid among adults...
In your article you cite the Swedish study, Lundburg-Morris, et al, in the British Medical Journal. While you have accurately summarized the authors’ findings you have not put these results into context or pointed out the serious limitations of this singular study.
1) Though this large study found long Covid risk reduction amongst the vaccinated cohort that was significant, the risk of long Covid itself was very low in both the vaccinated and unvaccinated; vaccination offered about a 1% reduction in long-covid. This means that if you choose to vaccinate, there is a 1 in 100 chance that you will derive benefit with regard to this end point.
2) It is well known that the risk of long covid is directly correlated with the severity of infection. In this study there was a large imbalance between the two groups: 60.2% of persons of unvaccinated infections were infected with the alpha variant compared to the vaccinated where only 3.5% of them suffered infection with alpha. The opposite is true with regard to Omicron, a less severe variant: Nearly 75% of the infections in the vaccinated occurred with Omicron compared to only 12.4% in the unvaccinated. The heterogeneity between the two cohorts was not mentioned by the authors but impacts the significance of their findings.
3) People who vaccinated within 28 days of getting Covid were excluded from the study. This is an arbitrary window of time and by doing so nearly 60 thousand of a total of about 360 thousand vaccinated individuals were not part of the analysis. The authors are free to do this, of course, but given that they chose the cut off time arbitrarily, they should have followed up on them with regard to the primary outcome, i.e. long Covid. This would have been the appropriate approach to providing transparency. In other words, how do we know that a lot of those recently vaccinated folks didn’t develop long Covid? This could have completely upended the vaccine effectiveness calculation.
4) A different study (see below) which looked at the same outcome, long Covid, demonstrated exactly the opposite: the primary series INCREASED the risk of long-Covid by 130% over remaining unvaccinated. In this study, both cohorts were matched with regard to the infectious strain. This is actually not so surprising. Antibody-dependent Enhancement (ADE) is a known phenomenon, especially with regard to the mRNA products. I would appreciate your commentary on this study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9767341/
Here's an answer to one of your questions, from Children's Hospital of Philadelphia: https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-safety/antibody-dependent-enhancement-and-vaccines
Anecdotally, and as a Biopharma researcher I realize anecdotes aren't data, my mother's college roommate said her Long COVID got much better after she got her booster shot in Fall 2023.
There have been reports of a few cases like this with vaccination, primary or booster.
Which booster?
The most recent booster to be approved in the USA
Thank you for this excellent LC (aka, PCC) Research Roundup. You once again manage to provide the exact information/insight I want, in the form that I want it.
I was very worried about long covid, because I have a hyperactive immune system, ‘long’ Epstein Barre, and Hashimoto’s. I finally had covid, took paxlovid, tested positive for 24 days with one negative day in the middle. For three weeks after testing negative again, I was exhausted all the time. I went to my integrative medicine MD and she recommended a three week, once weekly, course of IV NAC. It was amazing. Definite and significant improvements in how I felt and how quickly I was getting better after the first two treatments. Here is a link to one study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390689/ Of course, it was not cheap ($450 a treatment) and not covered by insurance, but so worth it.
I encourage folks with long covid to read Nicole Sachs and read about TMS/MBS and the brain-body connection. Many, many people have found their PASC symptoms go away once their nervous system moves from fight or flight to rest and repair (even things like ME/CFS, POTS, IBS, etc). Dan Buglio, Howard Schubiner, and Alan Gordon are other great places to start to learn about the science behind mind-body conditions.
One of the witnesses at the Senate hearing on Long COVID today made an important point about brain-body issues. She said in addition to brain-body issues, there are body-brain issues. A hallmark of Long COVID is neuro-inflammation, which is known to have damaging mental health effects. The upstream biological drivers have to be addressed first.
Some of us find the alphabet soup daunting! Could you spell these out please?
Tension myositis syndrome and mind body syndrome.
Thank you for keeping us up to date! I'm still trying to wrap my head around risk assessment and what can be done to avoid getting LC other than simply praying that the "Russian Roulette" of covid doesn't have a bullet with my name on it. I'm getting the latest boosters, still limiting social interactions during surges, eating outdoors, and masking in most public indoor spaces. Started using Enovid too, but its efficacy is not proven, so it's more of a placebo effect thing.
Thanks for addressing Long Covid. I really want to hear more about this subject as time and studies go on.
This is the first mention I’ve seen that vaccines can prevent infection at least initially. Can you please provide a source for this?
It's not a binary question. IIRC the first vaccines prevented up to 60% of infections by variants up to Delta in healthier and/or younger cohorts. Protection was substantially less in older cohorts with comorbidities.
Here's a reference for a more recent meta analysis that suggests the first vaccines were only about 20% effective in preventing infection against the Omicron family (https://www.mdpi.com/2076-393X/11/2/224)
The point is that 60%, even 20%, is not zero.
Thanh’s very much!
Can I assume that all or most information on vaccines and boosters and their effects on long Covid are from mRNA vaccine studies and not Novavax?
This is a good question. I admit I haven't paid attention to the *type* of vaccine in these studies. Given mRNA and Novavax reduce infections (in short term) and reduce viral load, I would assume no meaningful difference in long Covid
Thank you, Dr. Jetelina. One other question about the two types of vaccines –why the recommendation for mRNA boosters but not the protein (Novavax) vaccine, as both reduce infection and viral load "in the short term"?
Dr. Jetelina,
I'd love for you torevied Dr. Seheult's Medcram session on "Photobiomodulation for Long Covid". Interesting review from 4 months ago looking at near-infrared light therapy. https://www.youtube.com/watch?v=lLDYNoIVLmk
Very different from anything I learned in Med School!
Graham Barden MD FAAP