Possible impact of functional active gpcr-autoantibodies in long Covid(iovs.arvojournals.org)
iovs.arvojournals.org
Possible impact of functional active gpcr-autoantibodies in long Covid
https://iovs.arvojournals.org/article.aspx?articleid=2781044
52 comments
Thanks - I've changed it to the original title now (or rather, a truncated version to fit HN's 80 char limit).
Submitters: please follow the site guidelines, which ask: "Please use the original title, unless it is misleading or linkbait; don't editorialize."
Submitters: please follow the site guidelines, which ask: "Please use the original title, unless it is misleading or linkbait; don't editorialize."
I couldn't tell from the abstract (is there a link I missed), but I suspect that the test for GPCR-autoantibodies has a baseline (e.g. to test positive you must be 2-sd above the mean). From that if all 76 test positive you can know without a control group that that is otherwise very unlikely and a strong signal of correlation.
yea, these people have had covid.
What is "Long COVID" and how was it proved that all participants in the study "have" it?
Long covid is ongoing chronic illness symptoms following a covid infection, including but not limited to fatigue, heart problem, lung problems, brain fog, and auto-immune problems.
By that definition, anyone experiencing chronic illness symptoms "following" (said another way, "after") a Covid infection has "Long Covid" - even if Covid had nothing to do with those chronic illness symptoms developing or continuing.
I think we need a better definition.
I think we need a better definition.
I think at this point diagnosing long covid necessarily involves trusting patients. If you had no chronic illness symptoms you were aware of, and then get covid, and then have chronic illness symptoms - that's long covid. Until we understand what it is better, there's not going to be any way to objectively test for it, or define it more clearly.
After two years of confinement I have exhibited several of the symptoms associated with long covid.
I have done an asymptomatic COVID, so by all definition, I do suffer of long COVID.
Of course it could also be due to the fact that I am just generally getting older, being more tired and having a bit more headaches. Also, like many people I am doing a bit less sports than I used to, and my alcohol consumption has increased. The economy has gone to shit and my stress level have increased. It's probably unrelated tho and I will assume that the cause of my aliments is COVID.
"Long COVID" was used to describe the leftover symptoms of people suffering from a very hard COVID infection, leaving their lung half destroyed. Even tho they left the ICU, they still weren't back to 100%, and that's perfectly understandable. It could easily be identified by looking at a scan of a patient lungs.
It's now used as a catch-all name for purely subjective and self reported symptoms, which are also caused by bad diet, lack of exercise, excessive stress levels. No amount of scan/x-ray/... can be used to diagnose it, which is extremely convenient.
I do believe that "long COVID" is real. I just don't believe that self-diagnosis is the right way to measure it.
I have done an asymptomatic COVID, so by all definition, I do suffer of long COVID.
Of course it could also be due to the fact that I am just generally getting older, being more tired and having a bit more headaches. Also, like many people I am doing a bit less sports than I used to, and my alcohol consumption has increased. The economy has gone to shit and my stress level have increased. It's probably unrelated tho and I will assume that the cause of my aliments is COVID.
"Long COVID" was used to describe the leftover symptoms of people suffering from a very hard COVID infection, leaving their lung half destroyed. Even tho they left the ICU, they still weren't back to 100%, and that's perfectly understandable. It could easily be identified by looking at a scan of a patient lungs.
It's now used as a catch-all name for purely subjective and self reported symptoms, which are also caused by bad diet, lack of exercise, excessive stress levels. No amount of scan/x-ray/... can be used to diagnose it, which is extremely convenient.
I do believe that "long COVID" is real. I just don't believe that self-diagnosis is the right way to measure it.
So how do you measure it then?
Because if you're saying "self diagnosis is the wrong way", but there is no other way yet, you're effectively saying you don't believe anyone who has it has it. And that isn't helpful.
Because if you're saying "self diagnosis is the wrong way", but there is no other way yet, you're effectively saying you don't believe anyone who has it has it. And that isn't helpful.
As per my message: we have the CT scan/Xray to the chest showing clear signs of reduced lungs capacity following a COVID infection. Let's call this "doctor diagnosed long covid".
We also have the other self reported symptom. Because it's crazy to give it the same name, let's give it another one. We might call it the "I am feeling less well than 2 years ago" disease. It's a very common one.
Now the "I am feeling less well than 2 years ago" disease might have many origin. COVID being one of them. But considering that it has been rampant for years before COVID appeared, it's unlikely that it is the main origin of it.
According to me, it's not up to patient to diagnose it, just like we don't let patient self-diagnose brain cancer after letting them read 5 health article on Google otherwise everyone would have it - you know that joke, since why shouldn't it apply to COVID as well ? And since "long COVID" is discussed everywhere online and in the media, so it's natural people will associate with that, that does not make it true.
We also have the other self reported symptom. Because it's crazy to give it the same name, let's give it another one. We might call it the "I am feeling less well than 2 years ago" disease. It's a very common one.
Now the "I am feeling less well than 2 years ago" disease might have many origin. COVID being one of them. But considering that it has been rampant for years before COVID appeared, it's unlikely that it is the main origin of it.
According to me, it's not up to patient to diagnose it, just like we don't let patient self-diagnose brain cancer after letting them read 5 health article on Google otherwise everyone would have it - you know that joke, since why shouldn't it apply to COVID as well ? And since "long COVID" is discussed everywhere online and in the media, so it's natural people will associate with that, that does not make it true.
"long covid" is also going to be a goldmine for research funding for years to come, so it's not surprising that the term remains so vague.
> If you had no chronic illness symptoms you were aware of, and then get covid, and then have chronic illness symptoms - that's long covid.
Why even have a study if you refuse to be more scientific than this?
Why even have a study if you refuse to be more scientific than this?
> If you had no chronic illness symptoms you were aware of, and then get covid, and then have chronic illness symptoms - that's long covid.
Or a coincidence.. Not an unlikely one either, given the broad and vague set of symptoms.
Or a coincidence.. Not an unlikely one either, given the broad and vague set of symptoms.
Sure, but until we know what it is and how to measure if you have it - there is no difference between a coincidence and it. Would you rather we tell everybody who says they have it they don't, or accept everybody's self-assessment? Because until we have a way to diagnose it using an objective measure, those are the options.
Perhaps we'll get one after we understand it better. Medicine rarely works from first principles.
It's likely that long covid and many chronic illnesses share a similar pathology. The symptoms are surprisingly clustered.
I personally share your skepticism of self-reported diagnoses for such a vaguely defined condition. But it seems to me that a key part of developing a better definition would be to perform investigations like those in the source article, studying people with self-reported Long Covid to identify similarities between people who report it and/or differences with those who don't. How else could you research something like this?
You're a loser.
Not sure why this is downvoted. I am not qualified to read the paper but I have the same question. My impression was that "long covid" was self reported and there is no way to medically confirm if someone is actually has "long covid"
That’s like saying there’s no way to medically confirm that someone has a sore throat. Of course we may wish to determine the underlying cause of the sore throat, but even if we can’t that doesn’t mean that someone doesn’t have a sore throat.
We don’t yet know the underlying cause of long covid symptoms, which is what research like this is trying to uncover.
We don’t yet know the underlying cause of long covid symptoms, which is what research like this is trying to uncover.
You can say that one has sore throat, or fever, or fatigue, or headache.
But if you say one has long COVID, you are describing a condition (possibly a new illness, but not yet?) with a wide range of symptoms that occur in different combinations in different people, it seems fine to ask for clarification about what sets it apart other than having gone through acute COVID (natural question, as a person who has gone through acute COVID can still subsequently fall ill with an illness unrelated to COVID).
It is sufficiently vague that I have the same question each time I see the term. Maybe this subthread-starter was sincere?
But if you say one has long COVID, you are describing a condition (possibly a new illness, but not yet?) with a wide range of symptoms that occur in different combinations in different people, it seems fine to ask for clarification about what sets it apart other than having gone through acute COVID (natural question, as a person who has gone through acute COVID can still subsequently fall ill with an illness unrelated to COVID).
It is sufficiently vague that I have the same question each time I see the term. Maybe this subthread-starter was sincere?
> reported by people who have had acute COVID.
Plenty of cases of long covid are linked to not-particularly-severe covid cases.
Plenty of cases of long covid are linked to not-particularly-severe covid cases.
Acute doesn't mean severe, it means short. I used it to distinguish from long/chronic.
Oh, interesting. I hadn't actually encountered that definition of acute. Looked it up. Seems like medical dictionaries lean towards defining acute as an opposite to chronic, while non-medical dictionaries include that and other definitions like "extremely sharp or severe; intense" - which is how I took it. Good to know, for talking to doctors.
What is long covid, then?
My guess is they corrected for the # of people reporting these symptoms before covid happened.
But I didn't read the article.
But I didn't read the article.
How can you medically confirm someone has depression, chronic pain, or anxiety? You can't with diagnostic tests but you can observe their behavior and ask them.
"Long Covid" is extremely similar to other post viral illnesses that have been observed for decades, just getting more attention now.
"Long Covid" is extremely similar to other post viral illnesses that have been observed for decades, just getting more attention now.
I can say my left toe is hurting from long covid and no one can deny that. But if you say my left toe is hurting from depression that won't be taken seriously.
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Well for a study trying to find biological markers of a condition, I imagine the only way to source people is by self reporting. Because they haven’t found the markers yet…
Maybe someone with a medical background can answer this: Does this mean that long covid could be treated by blocking certain protein receptors?
Most probably not, at least not based on this study.
First of all, GPCRs are a class of many different receptors present in many different cells and with vastly different downstream effects, nothing that could easily be reversed with a targeted pharmacological intervention. Secondly, if there are general anti-GPCR antibodies present, it is most likely that they would inhibit the receptors or lead to damage of the cells expressing the receptors. Activating autoantibodies do exist (a form of hyperthyroidism being a common example) but are not the norm, so additional blocking would not be indicated. I also have some questions about the study as such. First of all, this is only an abstract that doesn’t describe all of their methods, it absolutely doesn’t allow any conclusions. My field of research is not GPCRs so I can’t say whether it’s common in that niche but their choice of using an in vitro rat (this cross-species) cardiomyocyte assay for antibody detection coupled with the absence of a proper control group or seropositivity threshold (at least not mentioned in the abstract) immediately makes me want to see further data before I trust anything described here. Their presentation style also seems confusing to me at a first glance and making it hard to tell what they did. Would have to spend more time on this and with the proper paper to disassemble everything. It also seems odd that they would not investigate this further if they indeed believed it to be involved in Long Covid at the systemic levels but rather chose to publish this in an ophthalmology journal.
Another question: how common are GPCR-antibodies in non-covid patients?
Very common, no doubt. Targeting GPCRs is a very wide net, GPCRs are a huge superfamily of proteins.
> GPCRs are an important drug target and approximately 34%[6] of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018.[6] It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of the pharmaceutical research.[2]
> GPCRs are an important drug target and approximately 34%[6] of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018.[6] It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of the pharmaceutical research.[2]
I think just about everyone has some level of GPCR-antibodies present just that people with long-covid have much greater amounts of them.
There are experimental drugs that can neutralize AAbs. They were successfully tested on Long Covid patients, but this is very preliminary. See for instance
https://www.frontiersin.org/articles/10.3389/fmed.2021.75466...
https://www.frontiersin.org/articles/10.3389/fmed.2021.75466...
I don't think this is a cause, but an indicator of an auto-immune related condition.
Covid may trigger autoimmunity though: [https://www.frontiersin.org/articles/10.3389/fimmu.2020.5893... Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis). I wonder what long covid might be then...
This paper was from the journal "IOVS - Investigative ophthalmology and visual science". So, I sent a copy to my ophthalmologist and asked his opinion. He replied that he couldn't understand any of it.
Should I start looking for a new ophthalmologist?
.
Should I start looking for a new ophthalmologist?
.
No, of course not, unless you are funding him to research long Covid.
Some doctors are unwilling to admit when they don't know something. If he was like that, then maybe it would make sense to start looking for another ophthamologist.
Some doctors are unwilling to admit when they don't know something. If he was like that, then maybe it would make sense to start looking for another ophthamologist.
Maybe? Reading the abstract, it seems to make sense to me how this paper ended up in this specific journal. From what I understand, the authors were specifically looking at one ophthalmology-related long COVID symptom (impaired retinal microcirculation) and found a common marker that is linked to that symptom.
Granted, I have 0 experience in any medical field, but it doesn't immediately look like a red flag to me?
Granted, I have 0 experience in any medical field, but it doesn't immediately look like a red flag to me?
Where’s the control? 100% of long Covid patients also had 2 arms and 10 toes
I came here to say "sure. But what's the control group," and "this would be more interesting if 100% of non-long-covid sufferers didn't have the antibody."
Interesting work, but this seems like only the first half of the experiment. Would love to see the data when the experiment is completed.
Interesting work, but this seems like only the first half of the experiment. Would love to see the data when the experiment is completed.
Does this apply outside of Europe? Those website banners drive me nuts.
This paper here will fill in the gaps of why auto antibodies against GPCR could be a bad thing - initiating autoimmune disease.
"GPCRs are the largest superfamily of integral membrane proteins in humans10. GPCRs play an essential role in vertebrate physiology by sensing the external environment of a cell and responding to a variety of physiological stimuli11. For instance, GPCRs coordinate the cellular behavior involved in host immune responses."
" we suspect that the homeostasis of aab relationships, which are possibly a physiological part of our immune system, may break down, causing autoimmune disease."
https://www.nature.com/articles/s41467-018-07598-9
"GPCRs are the largest superfamily of integral membrane proteins in humans10. GPCRs play an essential role in vertebrate physiology by sensing the external environment of a cell and responding to a variety of physiological stimuli11. For instance, GPCRs coordinate the cellular behavior involved in host immune responses."
" we suspect that the homeostasis of aab relationships, which are possibly a physiological part of our immune system, may break down, causing autoimmune disease."
https://www.nature.com/articles/s41467-018-07598-9
I've tested +ve for many GPCR-autoantibodies, I had it done at the CellTrend lab. I've never had covid but my pre-existing ME/CFS was made vastly worse from the booster shot, I have particularly high count of ACE2-AAb which seems to be associated with covid, and or the vaccine. I have the genetic predisposition called hEDS and knew the risks when I took them. It's taken 3 months of many powerful and experimental drugs and I'm just starting to get back to my normal baseline.
To the people wondering where the control group is; most people don't test positive to GPCR-autoantibodies. I don't know where the threshold is set but the probability that all 76 long-covid patients test positive is otherwise rather low.
To the people wondering where the control group is; most people don't test positive to GPCR-autoantibodies. I don't know where the threshold is set but the probability that all 76 long-covid patients test positive is otherwise rather low.
The study looked at 76 long covid patients with no control group, so you can't make a general conclusion from it. This post is a waste of time unless you're interested in obscure opthamological research.