Unfortunately Dr. Topol, denial is a very strong human trait especially when there is a political agenda to do so. Thank you for your interest in Long COVID, your formal review publications, commentaries in the mainstream media, and updates and podcasts on SubStack. Moreover, you are correct that more translational work has to be funded to help the millions of affected individuals worldwide. Finally, we don’t know what the current deficits being documented for Long COVID mean for longer-term CNS sequelae in the affected individuals.
The only good things I can find with these depressing studies and editorials presented in today's NEJM (which I read a day early in print form) are :
1) A lot of potential for bias. In the first study, those people motivated to stay in the survey might have been suffering from long Covid and problems that compelled them to respond. In the second study we are talking about self-reported memory problems via questionnaire (higher scores=more problems reported, therefore the red line on top is worse), and so once again there is the same potential for response bias and recall bias for those people knowing they had Covid. Hard to "blind" that!
2) ACIP/CDC meeting today recommends that those over 65 should get a second XBB monovalent Covid-19 vaccine this spring. Funny timing. The trends Dr. Topol has always highlighted show incremental but ever increasing benefits with staying up to date with vaccines and boosters.
3) Ventilation, respirators/masks in tight situations, and antivirals are still good options on the table.
I'm sticking with my own plan to take antivirals and probably metformin, and agree with Dr. Leana Wen's OpEd in the Washington Post about the pathetic under use of Paxlovid.
The potential for increased risk of Parkinson's disease and dementia years or decades later remains to be seen, but we have early contours emerging, and precedents with influenza... so why not use every tool we have to reduce viral load and the number/severity of infections sustained? The RCT needed to "prove" beyond a reasonable doubt that staying up to date with vaccines, treating infections, and reducing exposures will confirm long term relatively neuroprotective effects will never happen, as it would need to sprawl over decades, really.
Intuition and informed leaps of faith are part of this imperfect art.
As one of these "victims" with symptoms that are persistent *but intermittent*, I want large scale surveillance studies NOW to identify what personal health data metrics (sleep from Oura, activity from Apple Health / fitbit etc etc) and DIET data (MyFitnessPal etc) produce changes!
Do not wait, NIH and other countries! Start studying this NOW! There's no reason at all for delay.
Remember ACT UP. The people who were dying said "STOP JUST *STUDYING* THE DAMN DISEASE! WORK ON FINDING A *CURE*! WE'RE DYING HERE!"
@Ryan McCormick. It’s always gratifying to recognize a true thinking physician/caregiver esp one who recognizes the potential for a repurposed drug to treat such a potentially devasting illness like acute and Long COVID. I also believe in “talking the talk and walking the walk”. I too have formulated my own plan of action for COVID19. While the data supports the value of a TIMELY prescription for Paxlovid for preventing serious morbidity and mortality, my own insights support a contention that Paxlovid is uniquely designed to help the immediate crisis and must be given within 5 days of symptoms or a pos test. Furher, the patient must have no potential drug-drug interaction restrictions considering the significant hepatic enzyme effects from the ritonivir component. Metformin is designated as an anti-diabetic medication for type 2 DM, thus by definition it would be prescribed off-label for COVID19 (and possibly as a foresighted PASC therapy), both in the context of repurposing. Repurposing got a “bad rap” when the debacles of hydroxychloroquine and ivermectin came on the scene early in the pandemic. Many ClinicalTrial.gov studies showed no benefit with either drug for any stage of COVID19. Metformin has demonstrated some benefits for acute COVID19 in some laboratory studies but it too is not yet FDA-approved for this purposed. That is perfectly legal, perfectly ethical and NOT experimental as some wags opine. The prescriber uses his/her best judgement and information about a drugs risks and benefits for the intended use (NOT always a specific disorder, but the target physiological processes for the drug’s efficacy) and he/she feels confident the risk/benefit is favorable. Such a prescriber is using reasonable care and judgement. Rigid adherence to evidence-based knowledge (EBM) and formal RCT’s, esp in the scenario of a novel pandemic virus isn’t really focusing on patient advocacy as I view it. My own plan of action utilizes hydroxyurea/hydroxycarbamide (HU) based on extensive study literature research but even more importantly the consistently positive outcomes from ~2,500 patient prescriptions provided gratis by 6 prescribers over these past 4+ yrs. The clinical evidence accumulation began in a controlled inpatient setting in early 2020 at which time there were absolutely no guidelines, no approved therapies EUA or otherwise and no vaccines to benefit victims. Later, as word spread, hundreds of prescriptions were written for acute and extended illness from COVID19 in the outpatient setting, many given early enough to avoid a hospital trip despite declining vital signs with increasing disabilities.
HU is FDA-approved for several other diseases far less common (not always orphan type disorders) than the pandemic viral disorder COVID19. HU has been available for decades, is inexpensive and to date remains an essential drug per the WHO attesting to its safety and efficacy in the context of sickle cell disease (SCD) whose numerous pathophysiologies are also evident in acute and advanced COVID19. Derangements addressed include tissue hypoxia, vasoconstriction and nitric oxide deficiency, endotheliitis including thromboembolic disease with cortical, cardiac (myocarditis, arrythmias, coronary occlusions), renal, gastrointestinal and respiratory dysfunctions. HU safety is further evident in SCD since it is often prescribed for a life-time of use starting as young as 6-9 mos of age as fetal hemoglobin starts to wane and RBC membrane deformities add to the diffuse inflammatory issues associated with a painful sickle cell crisis. HU therapy is effective even for such a brief 5 day protocol and was noted to give prompt and durable results in our COVID19 pos patients and many of which we have presented to the FDA via the website CURE ID designed to solicit such COVID19 case reports.
For interested readers any number of AI search engines. using HU in the context of COVID19, hydroxyurea, a7 nicotinic acetylcholine receptors (a7nAChRs) and post-acute sequelae of Covid19 can identify many of the current articles with both new and old information in the scientific literature. My biochemistry collaborators have published several papers describing the role of HU with its link to these critical a7nAChRs and the ACE2 receptor gateway. Another article linking to the ACE2 receptor binding domain is in process. Haven’t heard anything about this? It’s available and it’s not misinformation. Thanks for having faith and scientific curiosity Dr McCormick. Few of our colleagues want to delve into the intricacies of this novel virus and fewer still have any faith in repurposing such as you advocate for metformin, or hydroxyurea/hydroxycarbamide as my prescribing colleagues and I advocate. I remain committed to hear more about the basic science promoted here by Dr Topol and his guests like Michelle Monje. The immune networks, microglia, as well as a7nAChRs remain credible and plausible areas to link to the outcomes with acute as well as PASC .
And this is one of the many reasons (edited from "exactly") why I'm trying to avoid catching COVID19 for a second time. No doubt it will happen eventually. Here in NZ the XBB vaccine will be available from 7th March, and I've made a booking for that day as we have a fair bit of JN.1 around.
I have been struggling with LC and truly have been considering getting an assessment to see if I have ADHD because of my struggles with executive functioning. These studies feel depressing and also validating for my experience.
Thanks for continuing to report on this. I hope the medical community takes notice.
Unfortunately Dr. Topol, denial is a very strong human trait especially when there is a political agenda to do so. Thank you for your interest in Long COVID, your formal review publications, commentaries in the mainstream media, and updates and podcasts on SubStack. Moreover, you are correct that more translational work has to be funded to help the millions of affected individuals worldwide. Finally, we don’t know what the current deficits being documented for Long COVID mean for longer-term CNS sequelae in the affected individuals.
The only good things I can find with these depressing studies and editorials presented in today's NEJM (which I read a day early in print form) are :
1) A lot of potential for bias. In the first study, those people motivated to stay in the survey might have been suffering from long Covid and problems that compelled them to respond. In the second study we are talking about self-reported memory problems via questionnaire (higher scores=more problems reported, therefore the red line on top is worse), and so once again there is the same potential for response bias and recall bias for those people knowing they had Covid. Hard to "blind" that!
2) ACIP/CDC meeting today recommends that those over 65 should get a second XBB monovalent Covid-19 vaccine this spring. Funny timing. The trends Dr. Topol has always highlighted show incremental but ever increasing benefits with staying up to date with vaccines and boosters.
3) Ventilation, respirators/masks in tight situations, and antivirals are still good options on the table.
I'm sticking with my own plan to take antivirals and probably metformin, and agree with Dr. Leana Wen's OpEd in the Washington Post about the pathetic under use of Paxlovid.
The potential for increased risk of Parkinson's disease and dementia years or decades later remains to be seen, but we have early contours emerging, and precedents with influenza... so why not use every tool we have to reduce viral load and the number/severity of infections sustained? The RCT needed to "prove" beyond a reasonable doubt that staying up to date with vaccines, treating infections, and reducing exposures will confirm long term relatively neuroprotective effects will never happen, as it would need to sprawl over decades, really.
Intuition and informed leaps of faith are part of this imperfect art.
https://mccormickmd.substack.com/p/my-self-treatment-plan-for-covid
As one of these "victims" with symptoms that are persistent *but intermittent*, I want large scale surveillance studies NOW to identify what personal health data metrics (sleep from Oura, activity from Apple Health / fitbit etc etc) and DIET data (MyFitnessPal etc) produce changes!
Do not wait, NIH and other countries! Start studying this NOW! There's no reason at all for delay.
Remember ACT UP. The people who were dying said "STOP JUST *STUDYING* THE DAMN DISEASE! WORK ON FINDING A *CURE*! WE'RE DYING HERE!"
@Ryan McCormick. It’s always gratifying to recognize a true thinking physician/caregiver esp one who recognizes the potential for a repurposed drug to treat such a potentially devasting illness like acute and Long COVID. I also believe in “talking the talk and walking the walk”. I too have formulated my own plan of action for COVID19. While the data supports the value of a TIMELY prescription for Paxlovid for preventing serious morbidity and mortality, my own insights support a contention that Paxlovid is uniquely designed to help the immediate crisis and must be given within 5 days of symptoms or a pos test. Furher, the patient must have no potential drug-drug interaction restrictions considering the significant hepatic enzyme effects from the ritonivir component. Metformin is designated as an anti-diabetic medication for type 2 DM, thus by definition it would be prescribed off-label for COVID19 (and possibly as a foresighted PASC therapy), both in the context of repurposing. Repurposing got a “bad rap” when the debacles of hydroxychloroquine and ivermectin came on the scene early in the pandemic. Many ClinicalTrial.gov studies showed no benefit with either drug for any stage of COVID19. Metformin has demonstrated some benefits for acute COVID19 in some laboratory studies but it too is not yet FDA-approved for this purposed. That is perfectly legal, perfectly ethical and NOT experimental as some wags opine. The prescriber uses his/her best judgement and information about a drugs risks and benefits for the intended use (NOT always a specific disorder, but the target physiological processes for the drug’s efficacy) and he/she feels confident the risk/benefit is favorable. Such a prescriber is using reasonable care and judgement. Rigid adherence to evidence-based knowledge (EBM) and formal RCT’s, esp in the scenario of a novel pandemic virus isn’t really focusing on patient advocacy as I view it. My own plan of action utilizes hydroxyurea/hydroxycarbamide (HU) based on extensive study literature research but even more importantly the consistently positive outcomes from ~2,500 patient prescriptions provided gratis by 6 prescribers over these past 4+ yrs. The clinical evidence accumulation began in a controlled inpatient setting in early 2020 at which time there were absolutely no guidelines, no approved therapies EUA or otherwise and no vaccines to benefit victims. Later, as word spread, hundreds of prescriptions were written for acute and extended illness from COVID19 in the outpatient setting, many given early enough to avoid a hospital trip despite declining vital signs with increasing disabilities.
HU is FDA-approved for several other diseases far less common (not always orphan type disorders) than the pandemic viral disorder COVID19. HU has been available for decades, is inexpensive and to date remains an essential drug per the WHO attesting to its safety and efficacy in the context of sickle cell disease (SCD) whose numerous pathophysiologies are also evident in acute and advanced COVID19. Derangements addressed include tissue hypoxia, vasoconstriction and nitric oxide deficiency, endotheliitis including thromboembolic disease with cortical, cardiac (myocarditis, arrythmias, coronary occlusions), renal, gastrointestinal and respiratory dysfunctions. HU safety is further evident in SCD since it is often prescribed for a life-time of use starting as young as 6-9 mos of age as fetal hemoglobin starts to wane and RBC membrane deformities add to the diffuse inflammatory issues associated with a painful sickle cell crisis. HU therapy is effective even for such a brief 5 day protocol and was noted to give prompt and durable results in our COVID19 pos patients and many of which we have presented to the FDA via the website CURE ID designed to solicit such COVID19 case reports.
For interested readers any number of AI search engines. using HU in the context of COVID19, hydroxyurea, a7 nicotinic acetylcholine receptors (a7nAChRs) and post-acute sequelae of Covid19 can identify many of the current articles with both new and old information in the scientific literature. My biochemistry collaborators have published several papers describing the role of HU with its link to these critical a7nAChRs and the ACE2 receptor gateway. Another article linking to the ACE2 receptor binding domain is in process. Haven’t heard anything about this? It’s available and it’s not misinformation. Thanks for having faith and scientific curiosity Dr McCormick. Few of our colleagues want to delve into the intricacies of this novel virus and fewer still have any faith in repurposing such as you advocate for metformin, or hydroxyurea/hydroxycarbamide as my prescribing colleagues and I advocate. I remain committed to hear more about the basic science promoted here by Dr Topol and his guests like Michelle Monje. The immune networks, microglia, as well as a7nAChRs remain credible and plausible areas to link to the outcomes with acute as well as PASC .
And this is one of the many reasons (edited from "exactly") why I'm trying to avoid catching COVID19 for a second time. No doubt it will happen eventually. Here in NZ the XBB vaccine will be available from 7th March, and I've made a booking for that day as we have a fair bit of JN.1 around.
I have been struggling with LC and truly have been considering getting an assessment to see if I have ADHD because of my struggles with executive functioning. These studies feel depressing and also validating for my experience.