> By day 300 of follow-up, 93 (8.3%) of 1,126 participants said they had received a diagnosis of long COVID by a provider. The cumulative incidence of long COVID by day 300 in those who took a 14-day course of metformin was 6.3% (95% confidence interval [CI], 4.2 to 8.2) compared to 10.4% (7.8 to 12.9) in the placebo group, or 39.4% lower.
Interestingly, half of the participants in the study (which took place starting in December of 2020) were unvaccinated. The researchers noted that metformin appears to have reduced the viral load greatly. I wonder if that is equally true for vaccinated and unvaccinated patients. It would seem plausible (not a doctor) that the reduction in viral load is related to the lower incidence of long COVID.
Now that we're in 2023, and pretty much everyone is either multiply-vaccinated or has had COVID, the study might turn out differently. If anyone has looked into the paper/data, I'd be interested to know whether the benefit is equal among vaccinated/non-vaccinated.
If Metformin reduces the viral load, it probably does so throughout the entire body. Whereas intramuscular vacccination leads to good protection against serious disease through humoral (body serum) immunity, it does not, unfortunately, provide significant protection to the other immune compartments like the upper respiratory mucosal layer (served by a different set of antibodies than the humoral).
So this is good. This (and paxlovid) can help protect those remaining unprotected tissues of the upper respiratory that tend to be the first infected. It should be a good temporary mitigation until the USA and other countries approve of good intranasal sars-cov-2 vaccine boosters like India has (Innovac).
I like USSF's Qyndr vaccine candidate, it's an oral one. For mucosal immunity I've read that it doesn't matter whether the vaccine is targeting the upper-respiratory system or the gut.
3.4 million people die every year in the US. What makes these deaths acceptable but COVID a tragedy? And yes, many of those 3.4 million are preventable.
It's fine if you want to make a point about COVID deaths—go ahead and say what you mean to say. I get there are many things to be said. But it's unclear why you're involving my comment with your soapbox. The parent comment to mine was about "not thinking about COVID".
Why not just say what you mean to say in full? There is no need to try to put words into someone else's mouth to speak up for what you believe. You seem to simply be re-framing my comment in order to make yours.
One way to start is along the lines of "This makes me think of an aspect of [the topic] which is [...] and what I think about that is [...]".
(No one brought up or said any of those other deaths were acceptable. Nor did I say that COVID deaths were unacceptable or "tragic".)
Your comment itself carried implications. “Some of us think…” is aggressive, and it contrasts the “enlightened” view against others. And you assume that the OP was ignoring those deaths, when they simply said it isn’t at the forefront of their mind.
I was contrasting your admonishment of the OP against the millions of deaths that you, presumably, “ignore”. The thesis is, why is it that COVID is hard to ignore while the totality of all other causes of death are more easily ignored?
My point was, you and me and everyone ignores deaths to some extent all the time. And you were so sure of your righteousness that you had to reply showing the world how refined and caring you are.
One thing to point out--this study provides the first really solid evidence that Long Covid actually exists.
From Derek Lowe:
"An overarching point, though, is made in a valuable commentary in the same issue of the Lancet by Jeremy Samuel Faust: this effect against a placebo control really shows us that there is something there. Long Covid is looking less like a cloudy mass of speculation and shoulder-shrugging, and more like a problem that medical science can start to unravel, using the tools we already have"
There are literally thousands of studies about long COVID- unless you believe they were all hallucinations by people who shouldn't be in academia, this is very much so not the "first" really solid evidence. I've seen evidence of increased all-cause mortality, arterial stiffness, reduced physical fitness, and much, much more.
All of which is in the first place only necessary because a core pillar of healthcare is the neglect and misattribution of mind-affecting disorders as psychosomatic.
I know people after brain injury now being treated for "depression" instead of pituitary dysfunction that occurs in ~80% of cases.
I think you're misinterpreting it. The full quote:
> Long Covid is looking less like a cloudy mass of speculation and shoulder-shrugging, and more like a problem that medical science can start to unravel, using the tools we already have:
> When a disease is too poorly defined, it follows that it is almost impossible to modify either the incidence of that disease or the distribution of its outcomes—that is, unless the treatment effect is so great, and the true target population so common in the assembled denominator, that any corresponding signal dilutions are offset. The present study suggests that, even with definitions as amorphous and heterogenous as those currently in use for diagnosing long COVID, there was to be found within this study population an ample cohort of individuals with syndromes similar enough that disease incidence could be modified, and metformin appeared to achieve that. Furthermore, the finding that long COVID is modifiable, although here showing prevention, offers hope. . .
This is definitely the first time I've seen anything showing a reliable effect on long Covid. Pretty much everything else I've seen has been a collective shoulder shrug of "well, we saw this, and it's maybe something about Covid, but we really don't know, and we have no idea how to treat this" and a bunch of people saying "it's just a possible side effect of an infection, we've been seeing this for decades". I have no idea how you can dismiss this as something we already know and that this isn't a positive and meaningful step forward.
You’re not paying attention if you think this is the first evidence of long covid. There’s been significant strides towards understanding long covid in terms of microclots and viral persistence.
Parent is saying it's the first evidence of TREATMENT.
Incidentally, my bet is that many other viruses and bacteria have similar post acute symptoms. I wonder if these can also be measured and treated, perhaps even with metformin. I wonder how much of metformin's magical anti aging capabilities are actually due to fighting off latent infections.
Metformin doesn't have any "magical" anti-aging properties. It is effective for treating certain metabolic conditions such as type-2 diabetes but it has never been proven to extend lifespan in otherwise healthy humans (or any other higher primate). There are some significant negative side effects.
I meant the magical part as tongue in cheek. I guess that doesn't come across well in text. My conjecture is that the anecdotal or limited evidence could be conflated with an improvement of latent infections, which would be an inconsistent effect.
They’re quite clearly saying that the effectiveness of the treatment is actually “the first” solid evidence of the disease.
Which is wrong, it’s not the first, but it is also pretty darn good evidence to add to the pile, so it’s not that wrong. It’s just the evidence that appears to have convinced GP, which is cool to see happen in real time!
Not in places were vaccine rollout was quick and frictionless with good coverage, thus reducing probability of transmission of the main strain and early mutations.
I think a lot of people in Northern Europe have either never had covid or had a mild possibly unnoticeable infection
Essentially everyone eventually gets Covid, vaccination or not, it's just that it's not worth testing continuously to see if your zero-symptom-life is currently infected.
What? Googling "asymptomatic covid" seems to disagree with this assertion? Even the wikipedia page for it claims: "At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time."
I'm not sure I follow, honestly. If you are trying to hold colloquial use to a technical measure, good luck. Even https://en.wikipedia.org/wiki/COVID-19_naming has "While COVID-19 refers to the disease and SARS-CoV-2 refers to the virus which causes it, referring to the "COVID-19 virus" has been accepted." Meaning, that ship sailed.
More, https://en.wikipedia.org/wiki/COVID-19, clearly talks about people having the disease but not being symptomatic. Such that you may be building a false divide? Yes, the virus is different from the disease. That does not imply that you only have the disease if you have symptoms.
> referring to the "COVID-19 virus" has been accepted." Meaning, that ship sailed.
Not exactly, "COVID-19 virus" is more like [descriptor][noun], it's saying "the virus that causes COVID-19".
On the other hand I also agree that the general usage of "covid" unfortunately means the virus for most people, but I still try to push back on it (and always try to jump in with confusion like at the start of this thread) because it has real effects, for example this "revelation" that was treated as a scandal 8 months ago? https://www.youtube.com/watch?v=mnxlxzxoZx0
Those of us paying attention knew it the entire time because Pfizer didn't conflate the two terms. Their press release back in 2020 very specifically only talked about stopping the disease, not stopping the virus.
> That does not imply that you only have the disease if you have symptoms.
Not the GP, but I've heard their perspective before from others, i.e. in medicine the symptom is the disease (or that the disease is defined by the symptom). If you have some virus in you that never does anything, you don't have a disease.
Same. I'm not clear on if that is all diseases or not.
I'm also still unsure it matters for this discussion. Especially if we don't have a causal understanding of what moves you from not having symptoms to having symptoms.
It was also tested only in overweight and obese patients.
Pretty much most people are overweight and obese in the US as well, I wouldn't draw any results from this study for people at normal weight.
That is a terrible conclusion to draw. BMI is a horrible indicator of health and to say that this study has no merit to "normal" people is idiotic. Also the jab against people in the US doesn't have any place in a scientific discussion of this study. Keep your prejudices to yourself next time.
BMI is fine as an indicator of "are you fat or not", UNLESS you are a very fit athlete. However being fat and being unhealthy aren't 1 to 1, contrary to popular bias and stereotypes. I've known plenty chubby and healthy people. They might not run marathons but get on with their lives just fine. Certainly it can raise your chances of being unhealthy but it's certainly not 1:1 as many online "experts" seem to claim.
There may be a misunderstanding about terminology here. COVID-19 is the clinical disease caused by the SARS-CoV-2 virus. If you are infected by the virus but asymptomatic then you don't "have Covid".
Can't say too much about it. Didn't really follow the whole Covid discussion and just continued my lifestyle. Eating healthy (fresh self-made food), doing sports and looking after a good mental state. Family and my circle did the same. Friends who have been vaccinated got Covid several times. But are also good now... My grandmom (89 years), also unvaccinated, didn't get Covid. Her sister got it (vaccinated). Both healthy now... Just let everybody do their own thing... The whole hate in the communities was unnecessary.
Attitudes like yours are why it kept spreading instead of petering out. I'm not saying that people need to get vaccinated, but I'm god damn sick of people not caring about spreading disease, whether vaccinated, or not. Humanity, as a whole, is in a war with disease. We don't need collaborators. All it takes for evil to triumph is for good people to do nothing.
> Healthy, young people who were intentionally exposed to the coronavirus SARS-CoV-2 developed mild symptoms — if any — in a first-of-its-kind COVID-19 human-challenge study.
That doesn't mean they weren't contagious.
> The first participants received a very low dose — roughly equivalent to the amount of virus in a single droplet of nasal fluid — of a virus strain that circulated in the United Kingdom in early 2020. Researchers anticipated that a higher dose would be needed to infect a majority of participants, says Andrew Catchpole, chief scientific officer of hVIVO. But the starting dose successfully infected more than half of the participants.
> The virus replicated incredibly rapidly in those who became infected. On average, people developed their first symptoms and tested positive, using sensitive PCR tests, less than two days after exposure, on average. That contrasts with the roughly five-day ‘incubation period’ that real-world epidemiological studies have documented between a probable exposure and symptoms. High viral levels persisted for an average of 9 days, and up to 12 days.
> Attitudes like yours are why it kept spreading instead of petering out.
Defining “why” can be a complex exercise, but let’s take a very simple approach: if there were not attitudes like the GP and everyone who could got vaccinated, would COVID have petered out? I don’t think so.
It’s plausible that, if enough production capacity had existed to rapidly vaccinate, say, 85% of the world population, evenly distributed, that it would have worked. But getting a uniform 85% was never in the cards, and, starting some time in 2021, the vaccine was nowhere near effective enough for a two-dose series to suppress transmission even with 100% coverage.
Sorry, but the idea of eliminating Covid with the vaccines we have was a nice fantasy, but it was not going to happen.
(If the vaccine were much better and had good worldwide coverage, then maybe. The smallpox vaccine was good enough. The measles and chickenpox vaccines are plausibly good enough. The oral polio vaccine might be good enough, but I have serious doubts that the strategy with which it’s used is actually appropriate. Somehow there does not appear to be community transmission of polio in New York right now, and I’m a bit surprised.
(People under about 23 years old in the US have generally received the injectable polio vaccine, not the oral vaccine. The injectable vaccine seems to be generally considered inadequate to prevent transmission. Maybe the under 23 year old NY population coupled with modern hygiene is not actually able to sustain an outbreak?)
My opinion doesn't lead to harm to other people, so you'll understand why I don't respect yours. Your right to swing your infected spittle ends where other people's mouths and noses begin.
> My opinion doesn't lead to harm to other people, so you'll understand why I don't respect yours. Your right to swing your infected spittle ends where other people's mouths and noses begin.
Don't you have the ability to stay home and avoid breathing near other humans if you're so concerned? I'm confused by that statement. How is demanding reduced freedom for him more just than simply exercising your own?
To be fair, Covid was never all that dangerous (in a statistical sense) for relatively young, relatively healthy people.
Of course, in the beginning that wasn't clear. And you might still want to get vaccinated, to decrease the likelihood of you passing the virus to your older relatives.
See my other comment. My circle consists of people up to 89 years. Thanks for the hint, but I am not convinced of the vaccine. I'll continue doing my stuff and it's my own responsibility.
I was very interested at the results of my spouse's antibody test! It was negative, and we thought for sure she had antibodies from infection. I have no scientific evidence, but she has genetic abnormalities in certain blood proteins, and I wonder if that assists with her resisting the infection!
antibodies are only measurable for a short time; long-term ability to defend is "learned" by the immune system but not measurable in any ordinary way; here in California coastal area there is a lot of social pressure about vaccination. Random people still insist that vaccination is important for healthy adults and sometimes under-18.
The fact that the 95% confidence intervals of two variables have some overlap doesn't mean there's a >5% chance that the expected values of the two variables are the same.
Consider two independent random variables X and Y; the chance that (a sample from X is above the 90th percentile of the true distribution of X) is 10%, but the chance that (a sample of X is above the 90th percentile of the true distribution of X AND a sample of Y is below the 10th percentile of the true distribution of Y) is 1%.
(disclaimer: with actual science the stats are a lot more complicated and you can't just assume they're independent and multiply the two, it's just a simplified example to give intuition about why overlapping confidence intervals don't imply what the parent thought, IANAstatistician)
Overlapping confidence intervals does not mean > x% chance that the two variables' expected values are the same. If the intervals overlap, the difference is not statistically significant.
Your example about random variables is largely misinformed. You're talking about things as if they are individual values. But we're talking about sample means. The probability that a sample mean for a large sample is above the 90th percentile is massively lower than 10%, and depends on n. The joint probability of getting two sample means above X threshold is irrelevant.
Confidence intervals don't tell you what the probability of the true mean being above X is. They tell you, bluntly, the range of values where the true mean could be, with 95% confidence ("If i were to do this experiment 100 times, based on the results I got, I would expect the true mean to be within this range")
You can play with some numbers and methods but you can rest pretty sure that a material effect size is probably not rigorously evidenced if the intervals overlap
> If the intervals overlap, the difference is not statistically significant.
Demonstrably false. Obvious counterexample: the study in the OP, which has overlapping confidence intervals and a statistically significant difference.
Proof: just calculate the 95% confidence interval for the difference between the two means. You can figure out what the stddev was from half the confidence interval divided by the z-score for a 95% confidence interval, 1.96, and you get 1.02 and 1.30 for the two groups. Then the confidence interval is:
(10.4 - 6.3) +/- 1.96*sqrt(1.02^2 + 1.30^2)
gives [0.86, 7.34].
This does not include 0, therefore the difference is significant.
> The probability that a sample mean for a large sample is above the 90th percentile is massively lower than 10%, and depends on n.
I was trying to give a basic intuition about normal distributions with a simple example, the distribution of one sample is a simpler example of a different normal distribution. Yes obviously the distribution of an estimate of X given lots of samples is not the same as the distribution of a single sample, I never claimed it was.
> You can figure out what the stddev was from half the confidence interval divided by the z-score for a 95% confidence interval, 1.96, and you get 1.02 and 1.30 for the two groups.
I'm not really interested in double checking your math, but you cannot derive the standard deviation of a sample mean confidence interval without considering the sample size. You seem to be making the same mistake again, confusing the Z score of a single value vs. the Z score of a sample mean. The standard deviation is of course going to be much larger. Why? Because you're actually looking at a difference of proportions where the values are either 1 or 0. The standard deviation is of course going to be much larger than 1%.
Ignoring that and assuming you meant to say standard error, where your math appears to work at a glance; in general, sure, overlapping confidence intervals don't mean that statistical tests of mean difference won't be significant. But... if you don't have that your effect size is probably pretty small. I would not put a lot of faith on these particular results as strong evidence of anything.
I would advocate for people to just look for overlapping curves.
> Yes obviously the distribution of an estimate of X given lots of samples is not the same as the distribution of a single sample, I never claimed it was.
If the inconvenience of having a vaccine are a turn-off for this demographic, I can’t imagine that GI distress (i.e. urgency) associated with metformin would be tolerable either.
> Men who filled metformin prescriptions before or after the three-month period of sperm development did not have offspring with a higher incidence of birth defects, the study found.
"impregnate" is not wrong per-se, but it is weird in placing the emphasis on only one of the two people required. Usually you'd say something like "trying for a child", I believe.
While more study is warranted, I believe the thesis is there is possibly a similar mechanism to how anti parasitics kill parasites during a specific window of their development cycle (with little effect outside of those windows).
As far as population studies go, this one seems pretty good though. There's a clear pattern attributable to the lifecycle of sperm, very large sample size, and pretty good controls.
I would definitely take this study seriously, and I don't usually pay a huge amount of attention to population studies.
>Now that we're in 2023, and pretty much everyone is either multiply-vaccinated or has had COVID
I'm a facilitator for a men's mental health talking group in my county. Sample size is small and not indicative, but there are a few people who are anti-vaccination, have continued to eschew popular science in favour of their trusted researchers, and are now assigning blame to almost any other person's illnesses as caused by "the vaccine".
Edit: I'm getting downvoted, so I should clarify -- I'm not agreeing with this person at all, I'm vaccinated and boosted.
Aside: one of the (anti-vaccination, anti-establishment) attendees has said that his (anti-vaccination, anti-establishment) trusted expert told him "the banks will collapse" on June 27th (he mentioned Santander specifically). So, now you know.
Well, I developed heart problems just after getting vaccinated so it's pretty hard for me not to agree when people speculate that some sudden death, severe illness or whatever at a young age may be due to the vaccination. I know I am biased, but how can I not be?
Firstly, I'm sorry you've developed heart problems. That sucks. I can't imagine how that feels in real life, but I can fully understand how it changes your perspective on a lot of stuff.
I should further clarify. My original comment was referring to a person who was saying, essentially, that if a person had been vaccinated, then any subsequent illness was a direct cause of the vaccine. His take was that any pre-existing condition was made worse, and the root cause of any kind of ailment was the Covid vaccine. Black & white, no room for discussion.
I can see how my comment could be misinterpreted in a number of ways. I don't subscribe to his stance, but I'm absolutely open to the increasing body of evidence of post-vaccine and post-Covid medical issues that have and continue to arise. I have a friend who was a whip-smart and highly capable gastric surgeon. She was fully vaccinated, then got Covid (positive tests), now has many symptoms of long Covid, and she's medically retired at 34. She has to have 10 minute snoozes every 30 minutes during the day. No diagnosed pre-existing conditions, she was in tip-top health.
I have absolutely no pro- or anti- agenda here, I was merely sharing some anecdotal evidence.
Most importantly, I hope you can find your way with your health stuff.
Emphasis on may, or might. Your experience is certainly valid, and I'm sorry you have to go through this, but it's still a sample of one with no theory of causation. If a certain percentage of people are vaccinated, and a certain percentage of people develop heart problems regardless of vaccination, a few of those people will develop those problems immediately after vaccination. Such things can be just statistical accidents. If I developed heart problems at 58, after years of poor diet and other bad habits, I don't think I'd ascribe it to one discrete recent event unless I was predisposed to believe that the two were related. Therefore, I think it's worth asking: did (or do) you have any such predisposition?
Eh, it's totally fair to draw a connection between Guillain-Barre, myocarditis, etc, and vaccination. They are all fundamentally the immune system overreacting and attacking your own tissues, and the vaccines are provoking an immune response. There's a clear mechanism for this to happen, so it's not shocking or a mystery.
The reason we accept this risk and get vaccines anyway is that all of these same conditions occur at higher rates when you are naively exposed to a virus. Myocarditis rates, for instance, are roughly 10x higher in any age group when you get COVID (without a prior vaccination or infection) than if you get a vaccine.
So if you aren't likely to be exposed to a particular virus, it's totally reasonable to not get vaccinated for it, just because there are side effects. I haven't been vaccinated for any of the various tropical diseases, for instance, because I don't travel anywhere. I haven't been vaccinated for rabies, because I'm not a vet and don't go spelunking. There's no point in rolling the dice on side effects when I have essentially no chance of contracting the diseases.
Once it became clear that everyone is going to be exposed to COVID, you stopped having the option to avoid rolling the dice on myocarditis or other immune-system disorders; it's just a matter of whether you want to roll the dice with a vaccine, or wait and roll them with your first infection, and have 10x the likelihood of getting hit with one of them.
Honestly, I didn't have any strong opinions and just did what everyone else did. Moreover, it was inconvenient that I could not enter to a grocery store without proof of vaccination so there is that. I am 26. I do not and never smoked, do not drink alcohol, maintain a healthy diet (do not eat sweets (except for dark chocolate sometimes) or anything that has lots of sugar, avoid highly processed foods, eat a decent amount of fruits, vegetables, nuts, fish, whatever), exercise regularly and never had any notable health problems prior to vaccine, I am not overweight not underweight. To the best of my knowledge, I never had Covid either.
Sure, I do not disagree that predisposition does not exist in such cases as you described, but I just feel bitter and miserable.
There is a small risk of developing myocarditis after being vaccinated, but the risk of dying of COVID in the US, for instance, was of 1.1% after being diagnosed.
I’m really sorry you are going through this. People didn’t have time to better test the vaccines to ensure their safety before having to use them to prevent massive loss of life due to the disease.
Perhaps we’ll find ways to alleviate the issues the vaccines caused, or even fix them, as the number of cases is significant and, with that, they can be better studied and the mechanisms better understood.
Not to mention the fact that the risk of developing a serious heart condition after getting Covid is massively higher than for getting the vaccine—including myocarditis. Though I would like to know what that comparison looks like if were only considering young, healthy people. That data still seems difficult to come across. But, I don't think there's any reason at this point to think that the relative risk of vaccine induced myocarditis vs covid induced myocarditis is significantly different in that demographic than any other.
Having done that comparison, really the only group where the vaccine wasn't protective against myocarditis (let alone everything else) was young men. And even then, it was more "Ehhh...?"
The myocarditis caused was also, generally speaking, milder than that caused by infection.
I don’t think “misinformation” is appropriate. Given the novel nature and chaos with COVID, the limitations with best effort, rushed information, etc there were a lot of different numbers thrown around for various cohorts, etc.
Figures like 1.1% were definitely cited, especially in the early days where the initial iteration of the virus devastated congregate living and other settings. It also took about 6 months for best practices for acute management of hospitalized patients were developed. Many people died as a result who would not have after 2021.
I got the data from https://ourworldindata.org/mortality-risk-covid which, recently, uses WHO data. In the case of the US, this is probably CDC’s. I probably should have noted that, initially, when COVID tests were scarce or non-existing because at that time a diagnosis implied symptoms. Still, the numbers are not as off as GP claimed. One number that still seems to hold is a 50% fatality rate for patients admitted to ICU (I just checked with a doctor friend)
> Aside: one of the (anti-vaccination, anti-establishment) attendees has said that his (anti-vaccination, anti-establishment) trusted expert told him "the banks will collapse" on June 27th (he mentioned Santander specifically). So, now you know.
I have started taking ivermectin to prevent this from happening so don’t worry about your money. You can thank me later.
Would these treatments work for other long-term viral illnesses?
I know Covid is getting the attention, but many have had long-term health effects from mono, influenza, and other viral illnesses. I was extremely sick for over a year and believe I may have had a severe Vitamin D deficiency at the time (it only got better once I finally crawled out of the house).
> It has to be noted that metformin has pleitropic effects that have shown up with a number of diseases. That simultaneously gives you some belief that the drug really could be working here too, while making the actual mechanism hard to pick out.
One thing metformin does is occasionally encourage cells to burn excess energy rather than store it. This may lead to extra cellular repair processes. I heard cancer rates were lower in metformin users and could extend life. Had my doc prescribe it to me 5 or so years ago.
I take it daily. There were mild GI side effects and weight loss at first, but my body adjusted and now it is BAU.
Haven't changed my lifestyle, can't know if it has made me more healthful. I still get colds and flu maybe once every other year.
Had a vaccine injury scare after the second jab. My health has been down since, can't know if Metformin is helping or hurting that situation - hopefully in the background helping me heal.
500mg twice daily, but I usually forget in the morning and take 1000mg before bed.
At least for my body, the troubled GI side effects faded over time. I never noticed any lightheadedness or fatigue by it unless I overdosed. But as I mentioned, I never changed my lifestyle and eat America-sized portions, so I suspect there's plenty of sugars and energy sloshing about and all systems have power.
I had long covid back in early 2022. It was not fun, despite being fully vaccinated and being extremely fit(run 20+ miles a week etc). It took me 3 months to shake the symptoms and I tried everything. Vitamin B IV injection(helped a little with splitting headaches I constantly had a month after covid). Vitamin D 5000iu daily, Fish Oil supplements, Zinc(had to stop from stomach issues), even tried MSM with Tumeric. I felt like alot of them did not make that much of a difference, taking NUUN(a electrolyte supplement seemed to work in fighting the fatigue and headaches). Glad there is something out there that finally works well.
so I contracted covid jan. 1st 2022, and was having symptoms in april of that year, I actually was admitted to the scripps long covid clinic, so I guess it was a bit longer than 3 months, memory was a bit fuzzy during that time. The Dr. who I saw at the clinic said on the scale of long covid symptoms mine were on the milder side, I couldn't imagine what moderate or severe would be like. Equally frustrating was the lack of tests that could detect it. The Dr. readily admitted this issue and said it made people who were suffering sometimes feel like imposters due to tests showing anything concrete.
Is there a good explanation of the mechanism of action? Metformin is also a Mitochondrial Complex 1 inhibitor, so I would be curious about Annonaceous acetogenins.
> We excluded people who were already taking one of the study medications or who had already received a COVID-19 treatment with Emergency Use Authorization by the US Food and Drug Administration.
Baseline characteristics table, Medical history section
> Only 17 (1.5%) of the participants had diabetes.
How many had pre-diabetes? Type-2 is a pretty serious diagnosis above a pretty significant threshold. Long-covid as defined can be somewhat marginal in characteristic.
Metformin also helps keep you under that threshold. Without Metformin my A1C is typically around 10 but with it I'm usually around 5. This complicates classification.
So I guess what I'm wondering is, how do we know we are treating lingering covid rather than pre-diabetes symptoms? Pre-diabetes is not symptomless and metformin is prescribed off-label to manage those symptoms. How many pre-diabetes symptoms overlap with long-covid classification?
> The primary method for ascertaining long COVID was participant-reported receipt of a long COVID diagnosis from a medical provider. Participants were asked whether a medical provider had given them a diagnosis of long COVID in follow-up surveys on days 180, 210, 240, 270, and 300.
Possible but untested. You may be interested to see this recent study that draws a mechanistic link (broadly, microglial inflammation) between the symptoms of long covid and "chemobrain" following chemotherapy [0]. The authors do suggest treatments proposed to restore cognition post-chemotherapy may also be applicable to long covid, e.g. metformin [1].
Nir Barzilai and a team of researchers are leading a large clinical trial to test the benefits of metformin in slowing the aging process, which is upstream of so many diseases that yeah, it could just be a cheap cure-all. Sadly requires a prescription in the US. But berberine is the off-the-shelf equivalent.
Yeah agreed. Is berberine really an equivalent though if the mechanisms are different and the not knowing metformin’s complete mechanism although it has a pleitropic effect? Metformin is heavily studied in comparison too.
The claim is that metformin greatly reduces viral load. If your long COVID is caused by the virus continuing to linger on 8n some tissues, as there is evidence might be the case for s9me patience, then it might. But if your long COVID is caused by microclots or lung scarring or other physiological damage caused by COVID, then no.
Makes sense. I found this too in a science journal:
> The exact pathophysiology of long COVID is unknown but is likely to be multifactorial, including the inflammatory cascade during acute infection and persistent viral replication. Mechanistic in-silico modelling predicts that translation of SARS-CoV-2 viral proteins is a particularly sensitive target for inhibition of viral replication, and previous studies have shown that metformin is capable of suppressing protein translation via mammalian target of rapamycin (mTOR) inhibition
And yet they have the clickbait headline. Overweight and obese people already have their body in a constant state of inflammation, and their blood sugar control probably isn't great either.
I wonder if they controlled for insulin resistance and prediabetes, which is related to obesity.
> Though not indicated for the treatment of PASC, the treating physician felt that her prolonged nasopharyngeal antigen positivity warranted the treatment. Indeed, the patient’s PASC symptoms fully resolved 3 weeks after completing antiviral treatment
It's not clear it's acting as an antiviral, in the classic sense of directly interfering with the virus, by directly bonding with and neutralizing viral proteins, or supplying lookalike proteins for the cells to make defective viral particles with.
Metformin affects glucose metabolism. It may be similar to how metformin seems to help with HIV infection; an immune cell infected with HIV goes into metabolic overdrive as it starts producing virus. Metformin seems to block that boosting mechanism through its effect on glucose, preferentially on the most over-driven cells. A similar story with certain glucose-fed cancers, which metformin is also used in treating.
I do wonder about treatment of people who already have long covid. I don't know if long covid is just lingering damage, or is the result of continuing low-level infection
I also wondered whether this could be a treatment for long covid. I don't know enough about it's etiology to say; however, like you I was downvoted without any response. Which is sad and not constructive.
You know a 1000 people who will personally tell you if they have a disorder that’s to begin with hard to diagnose and to make worse also hotly debated as even existing at all?
Given everything going against it, if two people actually have told you they have long Covid, what do you reckon the real number is?
I know several dozen people. One person who is still unable to work after COVID in late 2021, and a fair amount of people, myself included, whose condition substantially worsened for indeterminate reason during the last few years.
Most likely, the majority of people who are damaged by COVID aren't cases severe enough to label as "long COVID", and often just passed off as having become more depressed due to social distancing, etc. except they then don't recover with lifestyle improvement.
I suppose there are business connections among those 1000+, and I have a policy of never telling a business contact anything about my health (except "I'm on sick leave", if necessary). I suppose I'm not the only on doing that, so you most likely underestimate the occurrences.
I know a couple people in their 30’s struggling with long covid. One of them is a startup founder in SF and now has long covid and it’s been really terrible for them and their family. We speak often about it because I was out of work for months unable to function due to intense neurological inflammation. It greatly exacerbated what used to be a mild auto immune condition and I’m still traveling the country to get medical help and working from bed most days.
How would you know? How many in your extended network have Crohn's? Hashimoto's? Diabetes?
A lot of people with long covid don't realize there's a common syndrome for their symptoms. And of those who do know, most people don't broadcast their experiences with a long-term disability.
Significant numbers of my network have SOME kind of reported issues long after infection. Most common is respiratory issues – reduced lung capacity, difficulty breathing, running out of breath more quickly during exercise, etc. That's not to say any of these are official diagnoses, but we still know relatively little about the long term effects of COVID.
Yes, I know of friends and coworkers who have had to change career because they couldn't do their old job anymore. This after a year long recovery.
They aren't happy about it, they really want to do their old job, if only they could.
Then there are a few more who where home sick for 1 or 2 months. They all seem to have recovered.
People suffering from long covid certainly have a different experience. There's a range from "things smelled differently for a few months" to "I'm now functionally disabled due to fatigue". But without biomarkers that say you have this thing, it just looks like you're being lazy. So why would anybody tell you they have it and be judged?
There are literally hundreds[1] of literature reviews and meta-analyses about long COVID alone, based on *thousands* of publications about it. Go read some.
You don't get to go all "oh idk is there even any credible research about it" as if there's still any reasonable doubt that it's a real condition. There isn't.
And fun fact, both depression and "psychosomatic" symptoms have in recent years been increasingly linked to underlying physiological pathology and are no longer considered psychogenic symptoms by many, to a point where it's seeming like "psychosomatic" has all along been an excuse to blame people for conditions healthcare has been unable or unwilling to diagnose and treat.
> You don't get to go all "oh idk is there even any credible research about it" as if there's still any reasonable doubt that it's a real condition. There isn't
There's a lot of credible-sounding misinformation on this running around. Wouldn't be too harsh on OP.
It would be unusual if it wasn't real in some cases. Fatigue is common following viral infections, in general. It's not that unusual to be left very weak for months after a severe bout of influenza. The herpesviruses can do it too, as will most of the classics like measles, even a common cold if you're particularly unlucky.
Just intuitively, a virus causes damage to the infected tissues. The more severe/long-lasting the infection before recovery, the more likely some of that damage is going to be permanent in the form of scar tissue, rather than normal healing.
It almost certainly is associated with depression. Both in that if there is reduced lung function, etc. it may cause depression. But also in that depression can make an otherwise tolerable physical burden intolerable.
It's a respiratory infection. It would be surprising if every case was psychosomatic, given that other respiratory infections can also cause long term symptoms.
Vinay Prasad said I shouldn't bother putting on a mask when the east coast of the US was blanketed in wildfire smoke.
> First, recognize that some baseline exposure will happen no matter what. Even in your house, you still can smell smoked salmon. The baseline exposure may dwarf any portion remotely modifiable.
I guess none of us should wear masks because you can smell cooking salmon in your house?? Seems like this guy is not that trustworthy
It seems disingenuous to imply that the effects of COVID are not worsened by a high body fat percentage and / or poor physical health.
COVID is not a fat persons disease, but as with most detrimental health episodes, the negative effects are greater in people with high body fat percentages.
I would say OP was pretty disingenuous in implying that this was merely "fat people feel better from diabetes drug", when clearly it's not that they "felt better", it was that the medication reduced incidence of long covid when given during infection.
That's not the point GP was responding to though. OP was writing as if they just felt better because they were fat, regardless of whether covid had anything to do with it. That simply doesn't match with the study and just comes off like kneejerk fat shaming.
i think obesity is a risk factor but to call COVID a fat people disease is ignorant. There are many other risk factors (eg being immunocompromised) and you may get it (and long COVID) even without any risk factors.
> By day 300 of follow-up, 93 (8.3%) of 1,126 participants said they had received a diagnosis of long COVID by a provider. The cumulative incidence of long COVID by day 300 in those who took a 14-day course of metformin was 6.3% (95% confidence interval [CI], 4.2 to 8.2) compared to 10.4% (7.8 to 12.9) in the placebo group, or 39.4% lower.
Interestingly, half of the participants in the study (which took place starting in December of 2020) were unvaccinated. The researchers noted that metformin appears to have reduced the viral load greatly. I wonder if that is equally true for vaccinated and unvaccinated patients. It would seem plausible (not a doctor) that the reduction in viral load is related to the lower incidence of long COVID.
Now that we're in 2023, and pretty much everyone is either multiply-vaccinated or has had COVID, the study might turn out differently. If anyone has looked into the paper/data, I'd be interested to know whether the benefit is equal among vaccinated/non-vaccinated.