Roger Seheult, MD of MedCram explores elevated interferon levels associated with long covid. See all Dr. Seheult’s videos at: https://www.medcram.com/
(This video was recorded on February 23rd, 2024)
Roger Seheult, MD is the co-founder and lead professor at https://www.medcram.com/
He is Board Certified in Internal Medicine, Pulmonary Disease, Critical Care, and Sleep Medicine and an Associate Professor at the University of California, Riverside School of Medicine.
LINKS / REFERENCES:
Spontaneous, persistent, T cell–dependent IFN-γ release in patients who progress to Long Covid (Science Advances) | https://www.science.org/doi/10.1126/sciadv.adi9379
Viruses and interferon: a fight for supremacy (Nature) | https://www.nature.com/articles/nri888
Interferon Responses Could Explain Susceptibility to Severe COVID-19 (Medium) | https://medium.com/swlh/interferon-responses-could-explain-susceptibility-to-severe-covid-19-cc69a654b999
Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients (Science) | https://www.science.org/doi/10.1126/science.abc6027
Examination of autoantibodies to type I interferon in patients suffering from long COVID (Journal of medical virology) | https://pubmed.ncbi.nlm.nih.gov/37698062/
SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice (PNAS) | https://www.pnas.org/doi/10.1073/pnas.2302083120
Early Treatment with Pegylated Interferon Lambda for Covid-19 (NEJM) | https://www.nejm.org/doi/full/10.1056/NEJMoa2209760
Hyperthermia in humans enhances interferon-gamma synthesis and alters the peripheral lymphocyte population (Journal of interferon research) | https://pubmed.ncbi.nlm.nih.gov/3132509/
The biological activity of interferons in post-COVID syndrome (ERJ) | https://openres.ersjournals.com/content/8/suppl_8/240
Prevalence of persistent SARS-CoV-2 in a large community surveillance study (Nature) | https://www.nature.com/articles/s41586-024-07029-4#Sec2
Interferon Response in Hepatitis C Virus-Infected Hepatocytes: Issues to Consider in the Era of Direct-Acting Antivirals (International journal of molecular sciences) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177520/
Treatment of hepatitis C virus infection with interferon and small molecule direct antivirals: viral kinetics and modeling (Critical reviews in immunology) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882097/
SUBSCRIBE TO THE MEDCRAM YOUTUBE CHANNEL:
https://www.youtube.com/user/MEDCRAMvideos?Exposure to a more unhealthy diet impacts sleep microstructure during normal sleep and recovery sleep: A randomized trial=1
Get notified of new videos by hitting the bell icon
MEDCRAM WORKS WITH MEDICAL PROGRAMS AND HOSPITALS:
MedCram offers group discounts for students and medical programs, hospitals, and other institutions. Contact us at customers@medcram.com if you are interested.
MEDIA CONTACT:
Media Contact: customers@medcram.com
Media contact info: https://www.medcram.com/pages/media-contact?utm_source=Youtube&utm_medium=Video&utm_campaign=Video+Link+Clicks&utm_term=Insights+Into+Cirrhotic+Bleeding+of+the+Liver%2C+and+How+to+Stop+It&utm_content=CaBnPmyY5kE
Video Produced by Kyle Allred
FOLLOW US ON SOCIAL MEDIA:
https://www.facebook.com/MedCram
Tweets by MedCramVideos
https://www.instagram.com/medcram
DISCLAIMER:
MedCram medical videos are for medical education and exam preparation, and NOT intended to replace recommendations from your doctor.
#covid19 #interferon #coronavirus
Med.com welcome to another medc co9 update today we’re going to talk about a paper that was just published looking at long covid and interferon hi I’m Dr Roger schwell I’m the co-founder of medcram.com where we have continuing medical education accessible to MDS nurses Pas respiratory therapists Pharmacy students even EMTs
Join us at mc.com to get those informational videos if you need continuing medical education units or are just curious or you want to know more about a particular disease join us at medcram.com so let’s briefly talk about the immune system the immune system is made up of the innate immune system and the
Adaptive immune system the Adaptive is the part of the immune system that makes antibodies and takes a little while for it to identify the antigen and then form antibodies against it however today we’re going to talk about the innate immune system and the inate immune system is important because it
Recognizes certain molecules as being foreign and one of the major defense mechanisms that the inate immune system has against viruses in general is something called interferon or ifn as we’ll talk about and we’ve talked about this before it’s something that’s important in terms of fighting covid and
SARS K2 the virus that causes covid there’s been a number of articles about interferon and viruses in general and the fight for Supremacy we’ve covered this before the type one interferon response is important not only in SARS Toopy 2 but in the original SARS virus and also
In Ms and what has been emerging is evidence that if you cannot mount a good interferent response you typically get more critical types of disease whereas higher interferent responses acutely in covid-19 leads to more mild cases a number of papers have been published in the journal science looking
At this and you can see here that patients who had severe types of covid-19 have had inborn errors of signaling of interference the signaling was pretty low and the interferon Alpha in patients with covid-19 were very low and those that had antibodies against interferon their course was also very
Severe the quote here is that together these two papers that looked at the inborn errors of type 1 response and auto antibodies explain nearly 14% of all of the severe covid-19 cases in that cohort the question though is not about acute covid-19 today we’re actually going to talk about long covid or
Persistent covid-19 and a lot of the symptoms that go along with that such as fatigue shortness of breath muscle aches Etc there’s been a couple of papers that have looked at this one of the papers was the question of whether or not antibodies against interferon might be
The reason for people to have long Co there actually has been a paper that is published on that topic and in this paper which was not the one that we’re talking about today but was was published back in 2023 what they found here is that five long covid patients and three in the
Control groups actually had detectable circulating type 1 interferon Auto antibodies and so the conclusion was they did not see at least in this cohorts a causation for long covid from type 1 interferon Auto antibodies we have reviewed data that has shown that SARS kov 2 has a gene
Called Mac 1 which actually prevents the host from making interferon when they looked at specific types of bronchial cells and alveolar cells they noticed that the wild type virus which had the ability to make the gene product of Mac 1 cause lower levels of interferon in the cells that they looked at whereas
When they used the deletion Gene the ones that could not make the gene product there were higher levels of interferon at least in the acute phase but again what we’re looking at here is long Co but I’m setting this up so you understand the importance of interferon
At least early on in trying to get rid of the virus even more evidence in acute covid-19 this was a randomized control trial of almost 2,000 and what they found specifically was that a single subcutaneous injection of pegal interferon Lambda reduced the hospitalization rate by 50% highlighting the need for an interferent response
Acutely when the patient develops an infection with SARS K2 and then gets covid-19 we also showed how this was related to fevers and how at specific temperatures the body can release very high levels of interferon gamma specifically at 39° C or about 102° fahit it was also the basis for me
Theorizing that potentially hydrotherapy or raising the body’s temperature at least not treating fever fever reasonably so long as the fevers didn’t get too high could be a possible strategy at least acutely in people with covid-19 infections so with that in mind let’s move on to Long Co this is people
Persistently having symptoms of covid that would be headaches fatigue brain fog shortness of breath muscle aches things of that nature and this paper that was published by a Russian group in about 47 patients what they found is that the postco period was characterized by a less pronounced degree of
Inhibition of antiviral activity so we know that the virus reduces interferon and that after the postco period that that suppression of interferon is somewhat relaxed they go on to say here that patients with a more severe form of covid-19 have lower levels of type 1 and
Type 2 interferon but they say here that recovery of interferon status reveals positive Dynamics up to 7 months after disease but that even a longer period of time might be required for full recovery of functionality of interferon so interestingly in these patients not necessarily with long covid but in
Patients who have had postco syndrome as they name it here there was a reduction in interferon in these patients and that’s interesting as well because there’s this paper that was published in nature that looked at 93,000 samples from 990,000 people living in 66,000 households this was in
The UK from November of 2020 to August of 2022 when they were first sampled and being positive they were sampled once every week for four weeks and then once a month thereafter a number of these people who had been infected were persistently infected and still had viral antigens
Circulating it says here of the 381 persistent infections that we identified among participants of the on CIS that is the office of national statistics in the UK lasted for at least 2 months and two over 6 months in some cases the infecting lineage had gone extinct by the general population by contrast we
Only identified 60 reinfections by the same major lineage as the primary infection suggesting that immunity to the same variant remains strong after infection at least until the lineage has gone extinct so 54 out of 381 persistent infections lasted at least 2 months they go on WE estimate that one in a thousand
Of all infections and potentially as many as 1 in 200 may become persistent with intermittent High viral loads for at least 2 months the infection is suppressing interferon and the interferon is somehow necessary to rid the body of persistent viral infection specifically SARS K2 it would seem at least that perhaps increasing the
Amounts of interferon may help get rid of the last traces or remnants of that persistent infection let’s see if the data bears that out now we come to our feature article that was published just recently here titled spontaneous persistent te- cell dependent interferon gamma release in patients who progress
To long covid so we’re talking about long Co specifically this was a study that followed 55 patients with long covid fatigue this was after hospitalization for over 2 and 1/2 Years starting in August of 2020 and ending in July of 2021 severe long covid symptoms lasting
For at least 5 months after an acute bout of covid-19 you can see here some of the results based on the blood test and again we’re looking at interferon specifically and if you compare the amount of interferon in people who who are unexposed to those who are in Long
Co you’ll see here very clearly that in Long Co there are higher levels of interferon so realize that interferon is used all the time in chronic hepatitis C and when it is it can cause symptoms that are very similar to Long Co they’re very non-specific but they are similar
Similar symptoms like fatigue headache muscle aches body aches lack of energy and so the question is could it be that this elevation in interferon is high enough enough to cause the symptoms persistently but not high enough to get rid of the actual persistent infection we can see in patients who had acute
Covid-19 with the unexposed here being not exposed and then day 28 we see an increase in interferon and then at day 990 still elevated and then finally a reduction back down to the limits of detection here at day 180 that’s literally half a year later at 6 months
If we look at that data once again here are the unexposed here are those that had the virus but recovered we see that same data here but at the same time period of 180 days or greater we can still see that interferon levels are elevated and may be the cause of the
Symptoms of people with long covid if we look at people without long covid we can see here that there is definitely a statistically significant drop in interferon however interferon with people without recovery and it seems as though it’s all elevated but it’s always above the lower limits here of
Abnormal and if you look at the symptoms in the cohort of patients in this study you will see here what symptoms they had at their first visit and what symptoms they had at their final visit a lot of fatigue that is the major symptom a number of other different types of
Symptoms and of course being resolved is going to be the most common at the final visit brain fog got better fevers got better a number of things didn’t even exist like cough pneumonia anosmia myalgia palpitations got better rash stayed about the same fatigue got significantly better headache actually
Got a little bit worse in these patients so something that was interesting with these cohort of patients is that they got vaccinated and some of these people got vaccinated either because the vaccines became available or they might have gotten vaccinated because they thought it might help with their symptoms as there was
Some data that was suggestive of that early on they don’t mention in the article which vaccine was used or how many times they were vaccinated but they just looked at before and after they were vaccinated in terms of their symptoms there was a reduction after vaccination back to that graph you can
See here before vaccination and after vaccination there was an improvement and one has to wonder whether or not vaccination boosted the Adaptive immune system to help clear the virus so that the innate immune system didn’t have to produce interferon and cause some of these symptoms that we’re seeing
Here again we’re looking at interferon here before vaccination after vaccination and you can see here statistical significant drop in interferon levels before and after vaccination would have to do with time and we can see here that with time there was a reduction in symptoms so it’s unclear whether or not there was an
Increase based on just time or actually vaccination the other thing that is very clear is that compared to people at the beginning of the cohort versus those at the end there was a drop in interferon levels and you can see here that those that did recover eventually the
Interferon levels did go down this brings up a lot of interesting questions is the association between long covid symptoms and high and elevated interferon levels and resolution of long covid symptoms and low interferent levels is that causitive or is there something that’s causing both and I
Think that is a very good question it is possible that a persistent infection in the body is causing the symptoms of long covid because it is activating and increasing the body’s response in the form of interferon which is causing those symptoms but that when that persistent virus is eliminated
Eventually then the immune system is turning off that interferon and the symptoms are going away the question at this point is whether or not increasing interferon would be beneficial by getting rid of the infection or if binding or eliminating the interferon would get rid of the symptoms but on the
Other hand would make the infection worse one thing of interesting note the authors of the paper very specifically state that once the interferent was above a certain threshold there wasn’t a dose response curve in terms of the amount of interferon and the worsening of symptoms meaning that if somebody had
Higher levels of interferon and therefore symptoms increasing the interferon might not necessarily increase symptoms at least there was no evidence of that in this publication just so everyone’s clear hepatitis C is also a similar situation to what we’re seeing now in SARS Co V2 SARS K2 suppresses interferon production
In the cells in the acute phase and then in the persistent phase we see an elevation in SARS K2 especially in Long covid patients as we just talked about the same thing happens here in hepatitis C notice it says hepatitis C virus inhibits interferon production in infected hepatocytes type three
Interferon production persists in hcv infected cells that’s exactly what we’re seeing in SARS kov 2 as a result interferon lambdas are expressed at high levels in livers with chronic hepatitis C infections several studies have demonstrated in cell culture models that interferon lambdas were expressed at higher levels than interferon betas in
Hepatitis C infected cells later it was found that only cells that are infected with hepatitis C Express interferon lambdas we have a situation where chronically infected cells with a virus that is persistent makes more interferon and the question would remain here as well is it possible that giving more
Interferon would actually help get rid of the virus and the clear answer in terms of hepatitis C is absolutely yes we have known for years that the way that we used to treat hepatitis C especially two and three genotypes was exactly with pegol interferon Alpha plus ribavirin as
Well so I would be careful in making the assumption that just because we see high levels of interferon in Long Co that somehow the answer is to reduce the amount of interferon remember that in people who have infections in general they get fevers let’s not make the same
Mistake by assuming that simply by getting rid of the fever as they did in the 1918 pandemic by dosing on aspirin that this is somehow going to improve outcomes in influenza there was an article about this research and they said here in terms of classifying long Co this study
Argues that the presence of interferon gamma could be used to classify long covid into subtypes which could be used to personalized treatment they say quote it’s unlikely that all the different long covid symptoms are caused by the same thing we need to differentiate between people and tailor treatments
Some patients are slowly recovering and there are those who are stuck in a cycle of fatigue for years on end and we need to know why Dr Krishna said Dr Krishna is one of the authors of this paper and for those that are interested in seeing where funding came from for this
Paper I post this and my thoughts on the topic are that clearly interferon is one of the very important markers of inflammation it is one of the tools that the innate immune system uses to deal with SARS K2 viral infections but I think this research is very important in
Understanding the effects of and the causes of long covid and based on this data it’s possible that many people who have long covid symptoms are probably having those symptoms because of persistent viral infections and if we can find some way of enhancing the immune system to deal with that
Persistent infection that might be beneficial in terms of ending the long Co symptoms obviously more research needs to be done and I’m sure that is in the process of being done don’t forget to join us at medcram.com for more continuing medical education units and these are useful for medical doctors nurses Nurse
Practitioners Pas PA students Pharmacy students and respiratory therapists alike or if you’re curious to learn more about diseases in general join us at medcram.com
