New Long Covid Breakthrough! First step towards a treatment?? Dr Gill

[Music] if you're affected by long covid there's a new paper out that you need to be aware of by Dr felic louu and others titled large scale phenotyping of patients with long covid po hospitalization reveals mechanistic subtypes of disease but what does this mean in simple terms and why should you care the thing is this study has identified not merely theorized or suggested that there are people with long covid who have patterns of inflammatory markers which can be detected on a blood sample okay so far so good but here's the kicker the patterns seem to correlate with different subtypes of long covid as well although the authors are quick to state that the study was undertaken to better understand the inflammatory processes which Drive long covid not to discover biomarkers of disease thing is that correlation of long covid subtypes does strongly suggest that this might be the first step towards a disease modifying therapeutic trial potentially now we know that one in 10 covid-19 cases leads to a degree of long covid so it's no surprise that there's an estimated 65 million people worldwide waiting anxiously for a test which can deliver a clear insight as to what's going on with their body and by my reading this study isn't that yet but I think this study is probably going to be one of the paper that we'll look back on as marking a turning point in our understanding of long Co so the study was led by Imperial College London and looked at 657 people who'd previously been hospitalized due to covid-19 infections which occurred more than 3 months prior to the study now that's important because 3 months is 12 weeks and that's considered to be the the cut off for where prolonged symptoms are now indicative of long Co of those 600 plus patients 426 still had at least one covid symptom whilst 233 had completely recovered now on the face of it that's vastly more than the 10% of patients who developed long covid which jars with my earlier statement however the hypothesis for this difference in symptoms is that this was not a general population study but actually was looking at Patients specific specifically who had been hospitalized due to covid and that's important because we're aware that those patients seem to be a to hire risk of developing long covid after their initial infection the team went with a slightly shotgun style approach so to speak looking for a wide range of proteins in fact 368 separate proteins these are specific ones that are known to be involved in immunity and inflammation now from my perspective when I'm dealing with an individual patient this this isn't the best approach as essentially you're throwing everything at the wall to see what sticks problem is you don't know if something is stuck because they should have done or if they've stuck just by chance given the large number of patients in this study this greatly reduces the chances of the team having picked out so many similar findings across so many different patients by chance so I say that so many different findings what did they actually find compared to the recover covered patients the long Co patient still experiencing symptoms had detectable patterns of blood markers consistent with immune activation was ongoing okay we kind of expected that from the title but what do they mean when they say immune system activation the study found two signals in fact there was one marker of inflammation of bone marrow cells specifically myoid cells whose role is to trigger other white blood cells but there was also EV evidence of an activation of the complement system now these findings specifically that compliment system activation perhaps give an idea why long Co has been such a tough nut crack because if you ask Medics which lecture was their favorite at Medical School very few are going to stick up their hand and say anything to do with the compliment system and those doctors who did unsurprisingly became blood doctors and are working hematology now I raise that point because when covid came around it was the respiratory teams the Intensive Care teams the cardiologists the A&E and general practice teams that ended up being the heroes Who Bore the brunt of the workload on the ground but that was because we were dealing with patient symptoms and it makes sense really if your patient can't breathe or their heart is doing something weird you really want to be talking to the heart or the lung doctor but now as we're digging into what's causing that 10% % of patients to remain ill it appears that the hematologists and the immunologists might hold the key unfortunately these guys and girls are some of the smartest doctors there are and unfortunately we don't have enough of them which maybe why it's taken so long to get these studies out so the compliment system is by all accounts thick textbook type medicine and as a GP remember I'm a bearer with a very small brain I'm going to try and break down what the compliment system does and why that's relevant to you I suppose the first part is explaining the name the complement system is so named as it complement or enhances the activities of two specific parts of the immune system that of antibodies and phagocytic cells so what happens is literally the body detects an infection antibodies are produced and they stick onto identify markers or antigens on the pathogen this and triggers a large Cascade of reactions which complement that antibody related immune system so whilst it's nice know where the name comes from how does activation of the complement system relate to the second finding from the study that markers of inflammation from myoid cells were also elevated why might that explain the subtypes of long covid that the authors thought they could identify in the study oh yes I I've not gone into that yet but the study suggested patterns of immune activation which could potentially differentiate five different phenotypes or symptomologies of long covid but we'll get to that in a moment with regards to the compliment system there are five things that happen where the body notices an infection or damage the tissues the first is what's called opsonization so here complement proteins bind to the surface of an infectious agent essentially tagging them for death by the body and this death is achieved by the immune system attacking those pathogens with nutrifil and macrofagos the second bit of the complement system is a relatively straightforward one inflammation but what does that mean for p s basically you get vascular permeability which allows cells immune cells to pass into tissues think when you get an infected wounds when it's beginning to ooze this is the result of inflammation triggered by the tissue injury and the infection the third part of the compliment system is what's called membrane attack complex formation which honestly sounds like something from a 1980s cartoon and actually might not be missing the point by that not because essentially it's a bomb that the immune system can produce that can be attached to the side of bacterial pathogens which then causes the bacteria to leak and burst so throughout this complement activation process we also have another system going on that's the activation of an Adaptive immune response basically this is about the complement system making blueprints of bacteria viruses and damaged cells and making that blueprint available to white blood cells specifically B cells which leads the B cell producing more antibodies to help mopet that infection and then the final bit of the compliment system is the cleanup teams you see when we've got an immune system reaction like this we've got all these proteins and antibodies and immune stuff flying around this part of the compliment system helps clear up all those leftover weapons of the immune system meaning we don't get tissue damage after the infections being dealt with and I think that is where the light bulb might go off for some people so it's fair to say that the complement system is complex and while lots of people haven't heard about the compliment system many are aware of diseases that occur when it goes wrong the big names that you might be aware of are antiphospholipid syndrome rumod arthritis and as everybody knows from house lupus one of the things that was particularly interesting about the findings from this study as we've just highlighted the complement system basically has its own cleanup Cruise and they're there to terminate activation and remove leftover ammunition After The Infection has been dealt with however with long Co it seems we get a continued activation of the compliment system and perhaps a breakdown in the cleanup cruise and first author Dr Phil L strongly highlighted that it's indicative that the range of long covid symptoms is as a result of active inflammation and again is that the compliment system going to Haywire or is it the cleanup part not working what we can say is the information from this paper and that whole idea that long covid is due to active inflammation does make sense with the conversations I have with patients I mentioned earlier when I highlighted five symptomologies or phenotypes of long covid had been identified in the study I don't think anyone's going to be surprised to see that they were fatigue cognitive impairment respiratory issues gastrointestinal symptoms and also interesting enough anxiety and depression However the fact that they were able to identify pattern which marked particular symptoms could be key for tailoring treatments to patients I say that because we see this with antibiotics you basically nuke the patient's own microbiome whilst treating that single pathogenic bacteria and in the shortterm that might cause an up stomach but we'll actually have lowlevel lasting effects for up to 3 months after you've taken those antibiotics when it comes to looking at ways to potentially modulate the patient's immune system which is relatively important we want to be as careful and as targeted as possible to reduce the risk of collateral damage so these patterns indicating different symptoms or presentations along covid might mean in the long term we can tailor specific treatments to specific patients and reduce harm from our treatments one of the big problems with long covid has been our lack of focus to treatments there's evidence plenty of evidence of microclot issues in some patients and we do see improvements with those patients when we treat them with anticoagulation but we haven't been able to ex conclusively prove what has triggered that inappropriate clotting in the first place it may be that ongoing issues with inflammation are likely to be one of those triggers for coagulopathies and now we' have a study that might not necessarily give us the specific Target but certainly gives us is a very good idea of where we need to keep looking for the answer to which end the authors of this paper highlighted might be able to use a series of drugs called il1 antagonists to treat lco and I'm sure no one's going to be surprised to hear that il1 agonists are used for conditions like severe Advanced rheumatoid arthritis personally I feel lco is a spectrum of symptoms related to coagulation problems inflammatory problems gut microbiome changes and possibly allergic mediative responses but you know what would tie all of these together an autoimmune system issue such as what this team are talking about here but and this is very important the team of this paper have highlighted that they can't be sure that the findings in this paper are applicable to all long covid patients so we're going to take all of it not with a grain of salt but with some por with some caution given the possibilities that these newly found blood markers suggest that fatigue in some covid patients might be responsible for inflammation it also opens up the possibility of running this same panel of tests against patients who might have been affected with other post viral fatigues such as me I raised the point do investigations by Dr Lou's team have given strong evidence that lco is post viral INF inflammation unfortunately we know that such inflammation such as when it's come from sign bar infections you know we've said you were fine you had EBV and now you've got post file fatigue can be incredibly difficult to counter but now we've got to Target it might be much easier for us to direct our medical Arsenal to identify treatments that could be directed towards General post viral information ultimately this to me was a really important paper and I think it gives a little bit of Hope to those patients with long covid so I I hope this has been a useful uh little overview for you if you'd like me to do more um chats uh like this when interesting papers come across my way drop drop comments uh down below and we'll see what we can do with that in mind take care and we'll see you in the next one cheer