Some of the criticisms here can be answered by the paper and the code. To handle the "green jellybean" problem of multiple testing, they apply the Bonferonni correction. (Actually, the code uses the Simes variant of Bonferonni, so I think the article wording is not precise but it's not a major difference.)
I believe the code has a flaw in that it does not apply a multiple testing correction to the confidence intervals in the diagrams. (See lines 3199-3217). This makes the diagram inaccurate but does not alter the number of symptoms that would meet the bar of corrected-p < 0.05.
The deeper challenge is of course that it is a retrospective study with synthetic controls, so it will not be a gold standard. I think the best criticism is the one they note themselves:
"Conversely, with the evolving awareness of long COVID, it is possible that patients with a history of COVID-19 may have been more likely than those without to access primary care and alert clinicians of their symptoms, which could potentially lead to an inflation of the observed effect sizes. This is potentially supported by the increased aHRs observed for symptoms such as cough, sneezing, fever and allergies among patients who were infected during the second surge of the pandemic, compared to those infected during the first surge"
How likely are you to go to the doctor if you symptom is reduced libido and you have no recent major medical issues? But if you have diverse symptoms AND recently recovered from COVID, you may be much more likely to seek a medical opinion.
My comments above are methodological and not at all meant to deny that people do suffer long after acute COVID. Some of the ratios (like anosmia being 6x more likely in COVID group) are pretty large and that to me would continue to merit further investigation.
Thanks for that. It's a shame no one posted the original nature link previously.
> How likely are you to go to the doctor if you symptom is reduced libido and you have no recent major medical issues?
What's your estimation on how likely this is? If someone had just recovered from the worst pandemic in a century, would they self-assess as having no recent major medical issues? It's an interesting question.
Everything you stated is based on emotional stances and conclusions. Medicine doesn't work that way. This was a pretty good study with a very large sample size.
The cohort included 486 149 people with confirmed SARS-CoV-2 infection who were not admitted to hospital, matched with a control group of 1.9 million people with no recorded evidence of coronavirus infection.
> People who tested positive for the virus reported at least one of 62 symptoms more frequently 12 weeks after initial infection with SARS-CoV-2 than those who had not contracted the virus.
It was also a self reported. Self reporting for something like this is probably going to be useless.
In fact what might be more interesting is using this as an opportunity to study med student syndrome.
EDIT: Looking at the quote again, less troubling than the self reporting part is the 62 symptoms, I mean how many of you know how much hair loss you've had over the past year vs 12 weeks. They did have a considerable control group, but I also know there are plenty of ways to massage data.
But seriously 62 different possible symptoms? This seems like a very wide list of possible symptoms cast over a very wide net of people.
Still, it's an observational study with no reasonable, plausible mechanism of action presented. Worst of all, the study participant were in no way blinded: they knew, from testing, that they contracted a virus that was the constant focus of fear and uncertainty and pushed by media, quite literally 24/7, for months.
UPDATE: I've read up a bit more about Long COVID. I believe a relative minority of people who suffered from COVID experience lingering health issues. I think Long COVID is currently ill-defined. The respiratory and cardiopulmonary symptoms make perfect sense given what is known about COVID. Other symptoms like mental fogginess make sense as secondary symptoms from respiratory and cardiopulmonary complications.
I still don't find this particular study convincing in its claims of hair loss and sexual dysfunction being mechanically related to COVID aside from the general stress of it.
As a layperson, I have some sort of cognitive dissonance calling it "Long COVID" as if it's a separate but related disease, or a continuation of the primary infection. People's bodies suffer long-lasting damage while successfully fighting off all sorts of infections. But I don't recall it being framed this way.
ORIGINAL: Like most people here in the comments, I'm coming at this report with a healthy amount of skepticism.
The relatively paltry numbers and self-reporting remind me of the folks in cancer clusters in Londonderry Township, Pennsylvania, who completely believe they're victims of the Three Mile Island accident even though it's scientifically impossible for that to be true.
I believe the symptoms are real. But about a million things can cause hair loss and sexual dysfunction, including stress. Perhaps the stress of getting sick during a pandemic when people are dying and you know you're infected with the same illness? The fear of the unknown? Seeing people survive with complications and worrying that the worst of your particular case is yet to come? The guilt from wondering why you were pardoned when so many others weren't so lucky?
I'm pretty sure there's historical precedent for psychological symptoms made physical among the survivors of pandemics throughout history.
That's not to say that there are no precedents of lingering disorders, for example encephalitis lethargica in the wake of the 1918 flu pandemic. But my layperson's application of Occam's razor is telling me this is more Morgellons than encephalitis lethargica given the data currently available.
I would be more than happy to be proven wrong about so-called "long COVID" if it meant there could be a more effective treatment than the complicated world of psychiatric healthcare. If there could be a pill or a shot that could relieve these symptoms, I'd be delighted to eat crow.
"A total of 486,149 non-hospitalized individuals had a coded record of SARS-CoV-2 infection [...]. From the pool of patients with no recorded evidence of SARS-CoV-2 infection, 1,944,580 individuals were propensity score-matched to patients infected with SARS-CoV-2."
Put another way, according to Johns Hopkins, there have been a total of 24,079,325 reported cases of infection in the UK. That means a smidge more than 8% of infected people are suffering from prolonged symptoms as they are defined in this study.
That is statistically significant, but not exactly overwhelming by my personal yardstick of whether or not I'd gamble money on it. Not exactly scientific, I know.
I wish there was a way to measure how many people would self-report these symptoms without having had COVID first. Unfortunately, those numbers aren't being collected.
This feels like another of those cases where some random guy on the internet intimates that with just a few moments' consideration they've uncovered a fatal flaw in a huge study (500k actual, 2m control) conducted and reviewed by experts.
Specifically to your implication - if you're suggesting the chronic stress came from having COVID, then it's a valid side-effect of the disease. OTOH if it's a background effect of the pandemic, then (naively) I'd suggest that with those cohort numbers it's naturally controlled for, as both the 500k and the 2m demographics both lived / are living through the same pandemic.
EDIT: if you're concerned with the tone of my first paragraph, please click on parent's profile to understand my phrasing choice.
Really? You don't think that living in a pandemic and also getting the disease associated with that pandemic wouldn't be an inherently more stressful situation than not getting the disease?
It seems like a potential confounder to me.
> EDIT: if you're concerned with the tone of my first paragraph, please click on parent's profile to understand my phrasing choice.
Fair - but remember that your negative tone is read by everyone, not just GP.
A woman I know in her early thirties experienced severe, sudden hair loss in the two weeks she had covid (the original strain). She'd never had hair loss before. It did grow back but it scared her half to death. She's had covid twice now, but not long covid.
Tack it onto the list of bizarre symptoms I guess.
One of my more bizarre ones was Reynaud’s-like symptoms in my feet during the winter. Scared me half to death thinking I was going to lose a toe or something and had to run my feet under a hot bath several times to bring feeling back into my toes.
Another one was odd susceptibility to bruising in my feet. I wore some tight shoes one time, the same shoes I had always worn before COVID (some running shoes) and the resultant bruising/swelling made me think I had deep vein thrombosis.
In both cases, after my long COVID symptoms mostly went away around 2-6 months after I got COVID, I’ve never had anything like it happen again before or since.
> Electronic health records of 2.4 million people in the UK from January 2020 to April 2021
I don't know when the UK rolled vaccines out en masse, but I'm guessing that most of these people were not vaccinated when they had COVID.
Also, if they're looking at records only through April, that means they would have had to have had COVID weeks/months before then, for the follow-up symptoms to be recorded by April 2021. That would make it even more likely that the people were not vaccinated before infection.
My understanding is that people who were vaccinated before infection are at somewhat lower risk of long COVID, so it'd be great to see a large study like this of vaccinated people.
Indeed. Unsurprisingly, they did make some notes about this in the study:
"We were unable to estimate the effect of vaccination and infection year on long COVID symptoms in our study due to the very short follow-up period among those vaccinated and infected in the year 2022 (median 8 (IQR 4–14) and 12 (7–16) days, respectively) compared to those unvaccinated and infected in the year 2021 (33 (16–77) and 64 (31–90) days, respectively). Furthermore, the majority (81%) of patients vaccinated before infection in our cohort were infected with SARS-CoV-2 within 2 weeks of vaccination, which would be before acquiring immunity from vaccination, thus restricting the validity of our data to assess the effects of vaccination on long COVID."
> ... it'd be great to see a large study like this of vaccinated people.
I, too, am very interested in further research in this area, because it will strongly inform my actions now and for the next couple of years. As noted above though, it's frustrating, but it sounds like it's way too early.
Readit News
Their code is public: https://github.com/AnuSub/Stata-and-R-codes/
Some of the criticisms here can be answered by the paper and the code. To handle the "green jellybean" problem of multiple testing, they apply the Bonferonni correction. (Actually, the code uses the Simes variant of Bonferonni, so I think the article wording is not precise but it's not a major difference.)
I believe the code has a flaw in that it does not apply a multiple testing correction to the confidence intervals in the diagrams. (See lines 3199-3217). This makes the diagram inaccurate but does not alter the number of symptoms that would meet the bar of corrected-p < 0.05.
The deeper challenge is of course that it is a retrospective study with synthetic controls, so it will not be a gold standard. I think the best criticism is the one they note themselves:
"Conversely, with the evolving awareness of long COVID, it is possible that patients with a history of COVID-19 may have been more likely than those without to access primary care and alert clinicians of their symptoms, which could potentially lead to an inflation of the observed effect sizes. This is potentially supported by the increased aHRs observed for symptoms such as cough, sneezing, fever and allergies among patients who were infected during the second surge of the pandemic, compared to those infected during the first surge"
How likely are you to go to the doctor if you symptom is reduced libido and you have no recent major medical issues? But if you have diverse symptoms AND recently recovered from COVID, you may be much more likely to seek a medical opinion.
My comments above are methodological and not at all meant to deny that people do suffer long after acute COVID. Some of the ratios (like anosmia being 6x more likely in COVID group) are pretty large and that to me would continue to merit further investigation.
> How likely are you to go to the doctor if you symptom is reduced libido and you have no recent major medical issues?
What's your estimation on how likely this is? If someone had just recovered from the worst pandemic in a century, would they self-assess as having no recent major medical issues? It's an interesting question.
https://xkcd.com/882/
Dead Comment
I expect more and more "normal/ongoing things" will be attributed to covid as time goes on.
I imagine the massive lifestyle and economic disruption would add to these problems entirely independent of infection, for instance.
The cohort included 486 149 people with confirmed SARS-CoV-2 infection who were not admitted to hospital, matched with a control group of 1.9 million people with no recorded evidence of coronavirus infection.
It was also a self reported. Self reporting for something like this is probably going to be useless.
In fact what might be more interesting is using this as an opportunity to study med student syndrome.
EDIT: Looking at the quote again, less troubling than the self reporting part is the 62 symptoms, I mean how many of you know how much hair loss you've had over the past year vs 12 weeks. They did have a considerable control group, but I also know there are plenty of ways to massage data.
But seriously 62 different possible symptoms? This seems like a very wide list of possible symptoms cast over a very wide net of people.
I still don't find this particular study convincing in its claims of hair loss and sexual dysfunction being mechanically related to COVID aside from the general stress of it.
As a layperson, I have some sort of cognitive dissonance calling it "Long COVID" as if it's a separate but related disease, or a continuation of the primary infection. People's bodies suffer long-lasting damage while successfully fighting off all sorts of infections. But I don't recall it being framed this way.
ORIGINAL: Like most people here in the comments, I'm coming at this report with a healthy amount of skepticism.
The relatively paltry numbers and self-reporting remind me of the folks in cancer clusters in Londonderry Township, Pennsylvania, who completely believe they're victims of the Three Mile Island accident even though it's scientifically impossible for that to be true.
I believe the symptoms are real. But about a million things can cause hair loss and sexual dysfunction, including stress. Perhaps the stress of getting sick during a pandemic when people are dying and you know you're infected with the same illness? The fear of the unknown? Seeing people survive with complications and worrying that the worst of your particular case is yet to come? The guilt from wondering why you were pardoned when so many others weren't so lucky?
I'm pretty sure there's historical precedent for psychological symptoms made physical among the survivors of pandemics throughout history.
That's not to say that there are no precedents of lingering disorders, for example encephalitis lethargica in the wake of the 1918 flu pandemic. But my layperson's application of Occam's razor is telling me this is more Morgellons than encephalitis lethargica given the data currently available.
I would be more than happy to be proven wrong about so-called "long COVID" if it meant there could be a more effective treatment than the complicated world of psychiatric healthcare. If there could be a pill or a shot that could relieve these symptoms, I'd be delighted to eat crow.
Wait, what?
"A total of 486,149 non-hospitalized individuals had a coded record of SARS-CoV-2 infection [...]. From the pool of patients with no recorded evidence of SARS-CoV-2 infection, 1,944,580 individuals were propensity score-matched to patients infected with SARS-CoV-2."
That is statistically significant, but not exactly overwhelming by my personal yardstick of whether or not I'd gamble money on it. Not exactly scientific, I know.
https://en.m.wikipedia.org/wiki/Dancing_plague_of_1518
[1] https://www.who.int/europe/news/item/13-09-2022-at-least-17-...
Both are well known to be caused by age.
Dead Comment
Specifically to your implication - if you're suggesting the chronic stress came from having COVID, then it's a valid side-effect of the disease. OTOH if it's a background effect of the pandemic, then (naively) I'd suggest that with those cohort numbers it's naturally controlled for, as both the 500k and the 2m demographics both lived / are living through the same pandemic.
EDIT: if you're concerned with the tone of my first paragraph, please click on parent's profile to understand my phrasing choice.
It seems like a potential confounder to me.
> EDIT: if you're concerned with the tone of my first paragraph, please click on parent's profile to understand my phrasing choice.
Fair - but remember that your negative tone is read by everyone, not just GP.
Dead Comment
> matched with a control group of 1.9 million people with no recorded evidence of coronavirus infection
Still could be lurking variables of course.
One of my more bizarre ones was Reynaud’s-like symptoms in my feet during the winter. Scared me half to death thinking I was going to lose a toe or something and had to run my feet under a hot bath several times to bring feeling back into my toes.
Another one was odd susceptibility to bruising in my feet. I wore some tight shoes one time, the same shoes I had always worn before COVID (some running shoes) and the resultant bruising/swelling made me think I had deep vein thrombosis.
In both cases, after my long COVID symptoms mostly went away around 2-6 months after I got COVID, I’ve never had anything like it happen again before or since.
I don't know when the UK rolled vaccines out en masse, but I'm guessing that most of these people were not vaccinated when they had COVID.
Also, if they're looking at records only through April, that means they would have had to have had COVID weeks/months before then, for the follow-up symptoms to be recorded by April 2021. That would make it even more likely that the people were not vaccinated before infection.
My understanding is that people who were vaccinated before infection are at somewhat lower risk of long COVID, so it'd be great to see a large study like this of vaccinated people.
"We were unable to estimate the effect of vaccination and infection year on long COVID symptoms in our study due to the very short follow-up period among those vaccinated and infected in the year 2022 (median 8 (IQR 4–14) and 12 (7–16) days, respectively) compared to those unvaccinated and infected in the year 2021 (33 (16–77) and 64 (31–90) days, respectively). Furthermore, the majority (81%) of patients vaccinated before infection in our cohort were infected with SARS-CoV-2 within 2 weeks of vaccination, which would be before acquiring immunity from vaccination, thus restricting the validity of our data to assess the effects of vaccination on long COVID."
https://www.nature.com/articles/s41591-022-01909-w
> ... it'd be great to see a large study like this of vaccinated people.
I, too, am very interested in further research in this area, because it will strongly inform my actions now and for the next couple of years. As noted above though, it's frustrating, but it sounds like it's way too early.
https://www.washingtonpost.com/health/2022/05/25/long-covid-...
https://www.nature.com/articles/s41591-022-01840-0
https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.51570
Deleted Comment