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Inhaled Steroid For Early COVID-19: Increased Clinical Recovery And Decreased Persistent Symptoms?

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Inhaled Budesonide, a steroid medication, for the treatment of early COVID-19. This new research study published in Lancet found that in early COVID-19 inhaled Budesonide may increase the probability of clinical recovery, decrease the risk for decompensation, and prevent persistence of symptoms (decrease the potential for Long Haulers?). We discuss what this medication is, the dosing used, and then will dive into the study. Check out the video for all these details and more!

Hey everyone welcome to another video here at whiteboard doctor thanks for joining us today quick disclaimer before we move on none of these videos are intended to be act upon as medical advice please pause the video here and read the disclaimer in its entirety before moving on channel plug here at whiteboard doctor our mission is to bring you interesting

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Do that linked in the video description and pinned comment stay well keep learning and back to them all right everybody welcome back to another video here at whiteboard doctor today we’re going to be talking about a therapy that has been discussed in the past but of which there’s a new trial published and it’s an interesting therapy it’s the use of an inhaled

Steroid a steroid delivered through an inhaler for the treatment of early covet 19. so this is a study published in the journal lancet respiratory medicine and it’s looking at inhaled budesini this is the name of the steroid in the treatment of early kovid19 and they’re calling it the stoic trial s-t-o-i-c why are we talking about this well those of you that

Have been following this channel you many of you probably know we have several hundred at this point videos and all things covet 19. a big portion of those videos are on the research behind varying therapeutics one of the big goals in the treatment of covid19 is early therapy right obviously at this point we have vaccines for preventative measures we have some

Therapies for later covid such as steroids but we still don’t have any widely used early therapies now i know we’ve covered a number of potential candidates on this channel but the point of these early therapies is to prevent the progression of the disease and clinical deterioration i think a lot of people feel frustrated with the notion that you get diagnosed

With covid and if your oxygen levels are normal you get sent home to take some tylenol and hope for the best and some of those patients you know end up decompensating at home and having to come back so i think people you know both health care providers patients and the general public are are craving and you know desiring fiercely a therapeutic that could be

Initiated early on in the kind of clinical progression of covid19 that may prevent worsening progression and deterioration of the disease so why inhaled steroids many of you i’m sure are familiar with steroids right dexamethasone prednisone methylprednisolone in the treatment of covid19 this is a therapy that is used in patients who are you know often hypoxic

Aka have low oxygen levels but the idea is that’s a systemic steroid you can take it in pill form or put it through an intravenous line an iv line is there a possibility that inhaling the steroid through an inhaler could also provide benefit and that’s what this study looked at inhaled steroids and hailed budesonide a clinical observation made early on in

The coven 19 pandemic was that it seemed that there was a lower number of copd and asthma patients who were being hospitalized with covid19 and this is much different than flu in flu we have very large numbers of copd and asthma patients affected but in covid19 it was observed that there seemed to be less copd and asthmatics being hospitalized with covet 19.

And some postulated that that might be secondary to 2 2 secondary 2 the use of inhaled glucocorticoids are inhaled steroids inhaled steroids are often a medication taken at home by patients to prevent their exacerbations of asthma and copd so because of this a hypothesis was generated that may be inhaled glucocorticoids remember glucocorticoid is another name

For steroid but that these inhaled glucocorticoids may actually be used to treat covet 19 and this was studied a little bit more in cell culture initially in vivo and they actually found that there was a decreased um level of sars cov2 viral replication and airway epithelium treated with inhaled steroids and they also found some evidence that inhaled steroids

May down regulate the ac2 receptor and the tmprss2 what does this mean well many of you are probably familiar with this for those of you that aren’t just a quick review here is a human cell and here’s the sars cov2 virus the virus that causes covid19 it has these spike proteins these as proteins and the spike protein attaches to the human ace2 receptor and

Then the human tmprs this is a protease comes and it helps cleave this interaction to optimize it and make it stronger and the stars cov2 virus uses that to infect the human cells so by down regulating ace2 and tmprss2 there’s some theor some would theorize that that would decrease the ability of the virus to infect human cells so there’s some in vitro some

Cell culture evidence to further support the utility of inhaled glucocorticoids for the treatment of covid19 how does that tease out clinically though in a study so this trial here published in the journal lancet it was a randomized trial meaning patients were randomized to either get steroids or not it was open label so people knew whether they were getting

The inhaled steroid or not and then it was a phase two trial it was done in oxfordshire united kingdom and they enrolled adults greater than 18 years old to be enrolled you had to have either cough fever or anosmia right this is decreased smell and it had the symptoms had to come on within seven days because they were looking for early treatment all right so

You had to be within seven days of symptom onset they enrolled patients from july to december of 2020 and the medication that they gave patients was a budesonide inhaler and this budestinite this is the inhaled glucocorticoid or steroid and the dose of the pudesinide was 400 micrograms in one puff or actuation and the prescription was two puffs twice per day

So this was a total of sixteen hundred micrograms per day of budesinide okay and then this was just for standard care which antipyretics things like tylenol and motrin the protocol that they had was that they’d have a nurse go to the patient’s house on day zero day 7 and day 14 after they were enrolled and they would do pcr swabs help them with a symptom

Diary check their pulse oximeter and check their temperature and then a nurse actually called the patient each day to make sure they were filling out things like their symptom diary checking their pulse oximeter and their temperature the primary outcome here so the main outcome they looked at was the need for these patients to go to either an urgent care or

Emergency department as well as those that got hospitalized so the main outcome to see if the inhaled steroid could prevent clinical deterioration or you know progression of disease the secondary outcomes were several this is actually quoted from the paper itself so it was clinical recovery as defined by self-reported time to symptom resolution it was viral

Symptoms measured by this formal common cold questionnaire and this other influenza patient reported outcome questionnaire blood oxygen saturations body temperature and then viral load so there’s a number of secondary outcomes in addition to these primary outcomes so on the left here we have kind of the graph of patients enrolled so they enrolled 167 patients

Initially but 21 of them were excluded because some already had inhaled steroids six declined and 12 were not in the geographic area that they could enroll in the study so that left 146 to be randomized 73 were randomized to usual care and 73 were randomized to budestini the inhaled steroid alright we can see that a few did not end up getting allocated and ended

Up being 69 patients in standard of care versus 70 patients in budaped as for the two groups we always want to know if they’re well um appropriated you know if they’re well matched you want to make sure that the treatment group is of similar age gender demographic comorbidities as the usual care group and what you can see here is that the age was fairly variable

It averaged about 44 and 46 but you can see here that it was 19 to 71 and this is actually useful right because this is somewhat of a you know i will say a nice spread of ages it’s a representative of patients who in the real world are getting covet 19. all right in addition to that they looked and they had about 50 percent males and females you know maybe

More like 60 40. the majority of these patients were white they had on average you know uh normal to slightly high bmi they were relatively healthy um to the degree that they did not have many comorbidities about an average of one comorbidity per patient duration of symptoms this is something that i think is uh is great so that average duration of symptoms

Before they started taking the buddha and i was only three days so they did actually get to these patients you know fairly early on in their symptom onset which is you know one of the goals of the study and they were successful in doing that most of them were sars cov2 positive but there were a few it looks like so ninety four percent were stars cov2 positive

But there were a few it looks like that were not all right presence of symptoms the majority had at least a cough followed by fevers headaches fatigue and so on so forth all right highest temperature recorded not fab or um yeah not febrile lowest oxygen saturation recorded they also did not have hypoxia right above well in cova there’s some debate on this but

Above 88 percent in those with long disease 92 percent of those without lung disease some in covid would argue 94 but nonetheless they’re above that and then their cycle threshold so their viral loads based on pcr was 32.6 and 31.8 um for those not familiar with pcr and cycle thresholds we’ve done a number of videos explaining that um we’ll link a playlist in

The video description going over that so check it out if you’re interested what did the study find what were the results so on the left here you have their main graph and what they’re looking at here is if we looked its probability of clinical recovery based on days and the budesinide group is in blue usual care is in red and what we can see here is that

The budestinite group starts to have a higher clinical recovery as time goes on and that remains persistently higher to a p-value of 0.007 which is obviously less than .05 which means it is statistically significant so there is a higher probability of clinical recovery as days went on in the budesonide group compared to the usual care group this equated to

A 91 relative risk reduction in ed visits and hospitalization so there is a decrease by 91 percent in the need to go to an emergency department or urgent care or hospital in the group that got budestinide equated to a number needed of treat to treat of eight meaning if you give eight patients with covet budestinide inhaler in the study at least you would

Prevent at least one ed visitor hospitalization interestingly is this here and it’s something i kind of want to pause on at day 14 the budesinide group only 10 percent still had symptoms versus 30 percent in the standard of care group which brings up the question of could this be of benefit in long haulers right if only 10 percent in the budestonite group

Still had symptoms at day 14 and 30 did in the standard of care group could that be an indication that maybe inhaled budestinide um also could prevent the kind of persistence of symptoms in long haulers and then also interestingly even though you saw some of these clinical outcomes that were different there was actually no difference in viral loads between

The budestinide group and the standard of care group adverse effects were not all that surprising four individuals in the budestine group endorsed a sore throat which sometimes happens when you take inhaler therapies and one did endorse dizziness so what we have here is a therapy with minimal side effects that does seem at least in this study to demonstrate a

Decrea uh decrease in the need to prevent present to an urgent care emergency department or to get hospitalized a decrease in the persistence of symptoms an increased probability of clinical recovery but then at the same time no difference in viral loads between the two groups so it’s somewhat of a mixed bag and to be transparent some of the differences between

These groups were quite small you know a day or two here or there but i i’m most intrigued by the cheapness of the therapy the safety profile of the therapy and if we can you know prevent clinical deterioration obviously that’s tremendously important so i think a larger study on this would be quite intriguing the other thing that’s really interesting as i said

Is this right here could it prevent people progressing to the um long hauler phase you know with persistent symptoms so i’m looking forward to additional studies on this therapy i think this study in and of itself shows promise but it obviously has a huge number of limitations you know it’s not blinded meaning patients knew if they were getting the inhaler or

Not getting it which can you know sometimes um change how people fill out surveys for instance if you’re not getting the inhaler maybe you feel like your symptoms have not improved and you fill out that survey in a more negative fashion whereas if you are getting the inhaler maybe you get a little placebo effect and you think you feel better and then fill out

The survey you know as a result of that so lots of limitations here but still a very intriguing study and one that we’ll have to keep our eyes on as time goes on to see if there’s you know further larger studies that follow this up as it is a you know relatively inexpensive therapy that has a fairly reasonable side effect profile and there is both you know in

Vitro cell culture evidence to suggest efficacy as well is now some trial data too so interesting stuff anyways we’ll stop blabbering hope this was helpful or interesting or informative or educational we appreciate you taking the time to watch it if you like the video give us a like if you want to follow along on the channel hit that subscribe button and hit

The bell so you get notifications and new videos come out we have a pinned comment with a bunch of different videos we’ve done in the past and in this video’s description we’ll link some related playlists and videos so definitely check those out we appreciate you all stay healthy keep learning and we’ll see you next time

Transcribed from video
Inhaled Steroid For Early COVID-19: Increased Clinical Recovery And Decreased Persistent Symptoms? By Whiteboard Doctor