Metformin shown to prevent long Covid
cidrap.umn.edu
cidrap.umn.edu
> 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.
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"
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.
> 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.
https://cardiab.biomedcentral.com/articles/10.1186/s12933-02...
For this pathology long covid can be treated with so called triple therapy for instance
https://medhelpclinics.com/uploads/files/anticoagulant-tripl...
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.
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!
I understand the distinction you are making, and that's why I said semantics aside.
https://pubmed.ncbi.nlm.nih.gov/3320358/
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.
But none of them had a placebo group as far as I know.
If another one did, I'd love a reference.
Isn't this the most common demographic?
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.
No symptoms = not having COVID-19, GP was using the term correctly.
Conflating SARS-CoV-2 with COVID-19 is a big annoyance I have with the general usage of "covid".
Has terminology moved on?
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.
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.
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.
SARS-CoV-2 "referring to the virus" is for things like "SARS-CoV-2 has a number of receptor binding sites..."
If you're talking about what a person has, even if it's mild or largely symptom free, we use COVID-19.
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.
So it would make sense that the folks whom benefited tended to be overweight.
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.
Do keep in mind that having been lucky so far doesn't necessarily prove that playing with fire is safe.
https://www.nature.com/articles/d41586-022-00319-9
> 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.
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?
Come on now.
And no, I'm not a programmer. My job isn't remoteable outside of the occasional paperwork or Zoom meeting. I can't stay home.
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?)
Since you aren't discussing the topic I wrote about, I won't reply further.
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
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.
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.
Not number of samples. The sample size.
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).
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".)
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.
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.
https://med.stanford.edu/news/all-news/2022/03/birth-defects...
I would definitely take this study seriously, and I don't usually pay a huge amount of attention to population studies.
What the study shows is that if there's an effect it would have to be in the short time between the sperm developing and dying
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.
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.
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.
https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burd...
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.
We’re all laymen here.
Maybe 1% for highly at risk populations like elderly and immune compromised people but nowhere near 1% for the general population.
The myocarditis caused was also, generally speaking, milder than that caused by infection.
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?
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.
Between that and the "totally not caused by the vaccine" friends who had blood clots, gallbladder and appendix removals, etc... all in their late 20s.
All I'll say is I'm happy I never got it.
Pretty odd to cite something that has always mostly affected people under 30.
I have started taking ivermectin to prevent this from happening so don’t worry about your money. You can thank me later.
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.
https://www.science.org/content/blog-post/long-covid-shows-c...
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.
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.
12 weeks to recover from a viral illness, is unfortunately not special.
I believe most definitions are 12weeks+
WHO definition is 3 months from onset with symptoms for at least 2 months (so there could be a brief recover period after which symptoms return).
If it took you "3 months to shake the symptoms" you wouldn't meet WHO criteria.
Participants section of the paper
> 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.
See the outcomes section. Also, read the paper.
I.e. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537824/
> 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
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.
[0] https://www.cell.com/cell/fulltext/S0092-8674(22)00713-9
> 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
https://www.science.org/content/blog-post/long-covid-shows-c...
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.
Given everything going against it, if two people actually have told you they have long Covid, what do you reckon the real number is?
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.
I'm not sure if tinnitus is a form of long COVID, but I remain hopeful that my tinnitus can be fixed.