Some permanent long covid

hello and welcome to today's talk thursday the 4th of august now the largest study so far on long covered has just been published and it is quite disconcerting and when we combine this study large-scale study with previous smaller scale pathological studies looking at actual organ damage it puts it into context now it's not that common it looks like about 1 in 200 or 1 in 230 people are getting significant long coverage but some of those a significant proportion of those unfortunately may have permanent problems but let's get straight down to it here's the initial data

here across all variants of the virus apart from omicron this doesn't include omicron times so this is the original wuhan type the alpha type the delta type in the uk three main clusters of symptoms so people kind of go into these groupings central neurological cluster like nervous system type features is one next one is cardio respiratory cardio of course is heart respiratory as the lungs that's the next cluster and debilitating multi-organ systemic sort of inflammatory things including long-term fever and things that basically can affect any parts of the body muscle aches and things like that

but can be quite debilitating as the third group so regardless of the variance these are the types of long-covered clusters nervous system cardiorespiratory multi-organ systemic inflammatory that's what it fits into and and so what we'll do now is we'll look at these in turn and look at them in detail but just before we go on we will notice after this the vaccination didn't really seem to make any difference to the likelihood of quali the qualitative nature of the long coverage but but more on that in a minute now starting off with the uh central neurological

cluster anosmia loss of smell or abnormal or reduced smell very common fatigue now fatigue of course can have many causes but this is more the neurological cause of fatigue brain fog that sort of groggy feeling that you're not quite there i i've had this a few times um i had it after a bad ear infection and it's it's horrible it's almost like you're watching yourself on a video it's kind of a de-realization for me different people experience it differently of course but really very unpleasant uh symptom brain fog simple depression again terrible condition can be

terrible can make people feel absolutely wretched delirium is like a confusional state where you can be disoriented for time place person confusion difficult difficulty thinking and headache of course is is common in that in that group of symptoms and what the researchers found was that this this cluster this neurological cluster um was the uh the largest in both the alpha and the delta variants and it was the second in the uh the wild type variant now of course the wild type variant there was no uh vaccines at all it came and went the original wuhan

virus came and went without vaccination then alpha came uh vaccination came in during alpha and of course during delta people were very uh fairly comprehensively vaccinated so how much this is accounting for the difference it's it's unclear but uh the data clearly shows that this was the largest cluster in the alpha and delta times so most people have got this recently are presenting with this central neurological sort of presentation now we could look at about a dozen consistent studies because it's always good to compare and contrast and see if it makes sense so this is

a good study from the uk biobank which is a uk as it suggests it's where the uk collects biological data with many people contributing to that and the paper was called this um size coronavirus 2 is associated with the changes in brain structure changes in brain structure so this is consistent and the idea that i'm explaining this is this presenting this is this probably explaining some of the previous features now the uk biobank study found reduction in gray matter thickness now basically there's two sorts of matter in the central well in the brain anyway the

you know the central nervous system you've got grey matter around the outside white matter on the inside although there are nuclei of gray matter on the inside as well but the gray matter basically is nerve cells the nerve cell bodies and the white matter is basically the nerve cell fibers so if there's a reduction in the thickness of gray matter that indicates there's been a loss of gray matter a loss of neurocortical cells and these don't regenerate it it's that simple there is no significant regeneration no significant ongoing mitosis essentially no ongoing mitosis cell division

in grey neurocortical cells now of course all of the people with neurological symptoms won't have this loss of uh there's this loss of brain cells but we know that some do and this is concerning because it could well be um this is a potentially permanent effect so definitely the biobank study showed reduction in gray matter thickness that won't recover unfortunately if it's caused by loss of cells which it probably is tissue damage to the primary olfactory cortex that's where you smell with and again if there's damage to the nerve cells in the olfactory cortex that

probably won't recover significantly meaning people basically won't recover if this is true the meaning people won't recover their sense of smell to any significant amount and the uk biobank study also showed reduction in global brain size and again that may not recover so i think what we're seeing here in this neurological group as with other groups um we've got the people who are presenting the symptoms some of those symptoms are caused by temporary reversible physiological changes in the nervous system which will get better others of those changes are caused by permanent tissue damage in this

case in the brain which won't get better now we hope that most are in the physiological group where there's a pathophysiological derangement that will recover and we hope there's only a very small minority that have got permanent tissue damage but the bottom line is we don't know which is which at the moment so how many people some people are going to be left with long lifelong debilitating effects from this because of these neurological this neurological damage the proportion of those we simply don't know at the moment it is concerning we've seen this after previous pandemics

the the encephalitis lethargica that occurred after the 1918-19 pandemic post-encephalitic parkinsonism that occurred after that pandemic um i mean i can remember seeing people with that when i when i was a student i mean it's a long time ago but the oldest people were still around then from from the pandemic and um they had it for the rest of their lives so big unknown there how much is temporary pathophysiological pathophysiological derangement how much is actual damage similar picture really with the cardio um cardiorespiratory one uh this was the largest cluster in the wild type period

now again whether that's caused by the lack of vaccination or whether that's caused by a difference in the uh the viral presentation we don't really know symptoms may reflect lung damage here so dysmear this is this difficulty breathing shortness of breath going upstairs shortness of breath on exercise all of those things chest pain now if the chest pain is associated with um breathing um like when you take a deep breath in you get the chest pain that can be pleuritic or it can be the the pericardium if the chest pain is constant is more constant

or referred particularly to the left arm and into the jaw that can be cardiac so anyone with chest pain should get an immediate medical referral to to work out which it is because chest pain should always be taken seriously so different presentations of chest pain ongoing fatigue now again we looked at fatigue in the neurological um thing neurological section cohort and and fatigue of course can be neurological but fatigue can be cardiovascular as well so if you have damage to the heart and the heart's not pumping properly you're not pumping the blood around the body

the blood's not getting to your brain the blood's not getting into your muscles you'll have fatigue you put perfectly healthy young fit athletes on beta blockers that prevent the heart from contracting properly beta-blocking drugs they'll report undue fatigue it's due to reduced cardiac output again how much of that is due to temporary physiological derangement of the heart and how much of that is due to permanent damage of the heart muscles because if the actual myocytes the cells in the myocardium have actually died again they're not going to recover unfortunately so again some proportion are going

to get better or have degrees of recovery others are probably going to have lifelong disability as a result of this the proportions of which we don't know yet palpitations is another feature awareness of the the heart beating irregular or awareness of the heart whether it's fast or irregular or pounding or whatever it is consistent from a study in medicine we're only going to give one again clinical characteristics and outcomes of post-coverage pulmonary fibrosis this is the reference here i think it's published in nature um direct quote postcard 19 pulmonary fibrosis is a severe complication that

leads to permanent lung damage and death so um it's a bit the lungs are a bit like the liver if they've got great powers of recovery but if the scar tissue is is established like in the liver if cirrhosis is established that's not reversible for that part of the liver at least and again if there's fibrosis in the lungs the normal lung architecture the bronchioles and the alveoli and the blood vessels aren't going to recover the pulmonary fibrosis for that part of the lung is permanent so again it's hoping that most of these cases are

temporary pathophysiological derangements but a proportion will be inevitably unfortunately caused by permanent lung damage moving on to the next third category that's been identified um debilitating multi-organ uh symptoms now this could be anything i remember a lot of people had ongoing uh fever for example um in the early days but these are systemic inflammatory effects affecting the whole body inflammation in the whole body abdominal symptoms muscle pains but basically whatever is being affected um is the organ that will will present the clinical feature so it could be a very wide variety of clinical features presenting

in that and some of these people are really quite debilitated again how many are caused by tissue damage that may not regenerate how many are caused by tissue damage that will regenerate because some tissues regenerate much better than others liver for example is a superb regenerator whereas if the architecture of the kidney is lost that that's not going to regenerate the the muscle pain is also in there so again hoping that most of these are temporary but there's going to be a proportion we don't know how big a proportion whether it's a minority or a

majority of the cases that are going to be permanent unfortunately now regards vaccines a very controversial issue so i'm going to be careful direct quotes vaccination and long-covered direct quote from the the king's study that we're quoting we did not observe evidence of qualitative different symptom clusters in vaccinated versus unvaccinated individuals the vaccine made no difference to the quality of the symptoms that are experienced now the authors did admit did say that there was a limitation here because they hadn't taken fully into account people who are vaccinated and infected versus people who are infected then

vaccinated in the timing so they don't claim to have comprehensive timing data but in terms of the quality of the clusters and the symptoms it didn't make a difference surprising because previous studies have and there's always been this assumption that vaccination would reduce the likelihood of long covered but that's the direct quote we did not observe evidence of qualitative different symptoms clustering vaccinated with unvaccinated in either the alpha or the delta and of course with the wuhan wild type there was no vaccine so it doesn't come into it so that's that's the that's the main

points i wanted to get across um i'll just run through a little bit of background very briefly um but that's the main part of the video done now it's now evident uh that with post covered syndrome presents with heterogeneous profiles many different presentations it's not one disease so the need to characterize it to have personal care this was from the the covid symptom study 336 000 people who tested positive so we know that these were positive um now long covered lasted for more than 28 days uh post-coverage syndrome this thing lasts for more than 12

weeks they had 1459 with post-covered syndrome that's more than 12 weeks now that works out at 1 230 now this is encouraging because there's about 2 million people with long covered in the uk at the moment and it looks like most of them will not go on to have the symptoms for more than 12 weeks um is there a high proportion of people with permanent tissue damage in the post-covered syndrome lasting for more than 12 weeks than in those that recover in four weeks inevitably that is the case so we could be dealing with this

post-12 weeks um post-coverage syndrome after 12 weeks after the resolution of acute symptoms there's a high proportion of permanent injuries in those we still hope it's the minority but it will be a higher proportion they did all sorts of cluster analysis pretty pretty amazing study actually if you read it there's masses of material there i'm only scratching the surface they looked at different variants they looked at vaccination status uh they looked at all of these things symptom prevalence duration demography prior conditions uh comorbidities findings were actually more complicated so this is we've just done a

summary here but wild type variance they found four four main endo types alpha variant there was seven delta variant there was a delta variant there was five so um again we can't possibly go into this in the video uh but um an endotype is is um a sub-variant of a disease with a different pathophysiology in other words there is a whole host of different pathological features going on here giving rise to the different features yet nevertheless they can mostly be classified into those three the uh central neurological uh the cardio respiratory and the debilitating multi-organ

systemic inflammatory features but they're able to come across many more classifications indicating that this viral infection is is damaging a wide variety of people in a wide variety of ways their interpretation our classification may be used to understand the distinct mechanisms of the post-covert syndrome which is good as well as subgroups of individuals at risk of prolonged debilitation now just a quick word from the authors uh dr claire steves these data show clearly that post-coverage syndrome is not just one condition but appears to have at least several subtypes as we've said three main ones and

other ones underneath that understanding the root cause of these subtypes may help in finding treatment strategies of course because if we know what's going wrong in the body we're going to have a much better chance of fixing it moreover these data emphasize the need for long-covered services to incorporate a personalized approach absolutely personalized approach sensitive to each individual and dr uh dr keynes another author uh these insights could aid the development of personalized diagnosis and treatment for these individuals so as always it's good to understand the physiology that helps us to understand what goes wrong

the pathophysiology and the pathology and if we understand that we can we can work out the best strategy to treat these patients so let's hope that the proportion of people with permanent organ damage is remarkably small and the people with temporal temporary pathophysiological aberrations is remarkably large but right now we simply don't know that so there we go that's the latest on long covered for a minority of patients this is going to be a lifelong problem um we hope for the majority there's going to be good levels of recovery but if people have had the

symptoms for 12 weeks or more um we actually don't know that to any great extent as of yet and disappointing that the vaccines aren't making any qualitative difference to these to these uh syndromes so thank you for watching and um i think i think i haven't put it below for a while but um these are my books here um they're now free on pdf so this is if you if you're serious about learning about this kind of stuff this one's all on physiology how the body works lots of diagrams this one's all on pathophysiology how

the body goes wrong or the different bits and bobs of the body that go wrong with lots of diagrams took me years to write them so it'd be good if someone would read them and i'll put the pdf link for free downloads in the in the description okay thank you for watching you