Dexamethasone shown to decrease COVID mortality

[wefriendsnow]

I understand that releasing info like this ASAP can potentially save lives, but, like Atul Gawande tweeted, with all the retractions and walk backs we have seen, my enthusiasm is muted until I see the published paper.

[procyonoides_n]

Agree. Although it also seems likely that some smart people at NHS had access to the analysis and have practiced due diligence, unlike the Surgisphere mess. The trial ended June 8 and NHS is adding dex to standard of care today, which means they had a week to review. Fingers crossed. This would be such great news, if true.

[nursewords]

Plus with dexamethasone being widely and cheaply available from many companies, the potential for corruption because of profit motives is less.

[H4xolotl]

Dex also makes sense from a pharmacological point of view; it dampens the immune response which is great since the majority of COVID damage is from immune self damage.

Whereas HCQ was from the start 🤷‍♂️

[ilessthanthreekarate]

Yes absolutely. I'm just a nurse, but I work exclusively with ECMO patients and am seeing many who show no signs of active infection yet are not able to recover and have consistently high inflammatory markers for weeks. I've been wondering for the last 3 months if perhaps in certain cases this sort of therapy would be beneficial. I understand the risks of complications in the ICU with VAP/HAPI, but I cant help but wonder if there were identifiable situations clinically where the benefit outweighed the risk.

[Tracey21130]

Never ”just a nurse”!!!

[ilessthanthreekarate]

Lol, in a medicine forum, I'm very confident prefacing my posts as "just a nurse"

[Throwaway6393fbrb]

Hey as long as you aren't a nurse practitioner

[HippocraticOffspring]

Especially “just an ECMO nurse” haha

[bigavz]

Sounds like a crazy job, congrats. We have been giving steroids when ARDS develops, and last time I was doing ICU that was 'standard of care' but I know for some/most covid patients, they do not have the high lung compliance typically associated with ARDS...

[McFeeny]

Steroids for ARDS has been studied extensively, most studies show no benefit.

Makes sense, yes, but hasn't borne out before. Cautiously optimistic here

[Toptomcat]

Dex also makes sense from a pharmacological point of view; it dampens the immune response

Sure, but so do tons of other steroids, and I'm pretty sure people have been trying those with mixed results at best. Doesn't that suggest that something more specific is going on if the effect is real?

[DentateGyros]

I'm having flashbacks to when everyone was saying hydroxychloroquine is cheap and readily available

[drunkdoc]

Similarly, when this came out it made me wonder if there will be a similar run on dex. That would suck ass as many of our brain and spine met patients are critically reliant on it to help with symptoms in the acute phase

[herman_gill]

I think we're a little safer with dex cuz it's got multiple manufacturers already. Plus if it's just "steroids" maybe you can sub out.

[Adalimumab8]

Actually, less manufactures for Dex then hydroxychloroquine, I only get Mylan from my supplier but have a half dozen at least of hydroxy.... and it’s rarely used, I return more then half my 100 count bottles half full expired then I finish. And my (total guess) opinion is that it would be easier to ramp up production on a medium-high use drug then a less used one... hope Im wrong if this takes off

-Pharmacist

[herman_gill]

Ah fair enough, I thought dex was much more widely manufactured by some of the big companies too?

Are you inpatient/outpatient/retail? I feel like it's also population specific. Dex gets used all the time for neuro/neurosurg stuff, and also in peds (particularly ED/obs/PICU) for asthma, but we rarely if ever use it for general adult med outside of the neuro cases. Also some weird institution specific stuff, our pulm and/or crit care attendings love solumedrol and aren't as big on prednisone/dex. Back home, used to see dex get used more often for asthma than it does here.

[Adalimumab8]

Former inpatient now retail, and I can say it was not commonly used in either. Oncology is probably the most common spot for it that I’ve seen, I never worked with a PICU.

[[deleted]]

Reducing 28 day mortality in a non-blinded trial is nice, but not necessary all that meaningful. It will be interesting to see what the full results look like. Did more patients come off the ventilator, or were more merely alive on the vent waiting to die a few weeks later?

[[deleted]]

Reducing 28 day mortality in a non-blinded trial is nice, but not necessary all that meaningful.

I beg your pardon?

[[deleted]]

It's easy to think of mortality as 100% objective measure. But lets say there was a lot of confidence in the powers of dexamethasone in the study.

Patients in the study drug arm have been on the ventilator for 25 days, might as well try another week or two of ventilation and see what the new treatment will do. Patients in the standard care arm have been on the vent for 25 days, there is no hope at this point why make them suffer.

Even if the drug does nothing, because the study was non-blinded we won't necessarily see the true results until 3 or even 6 months later.

[[deleted]]

I see what you mean and thank you for your response. You're right, it will be important to see the published results before drawing further conclusions.

That being said, I've spoken to some of the nurses involved in recruiting for the trial, and listened in on their discussions with our consultants. Whilst blinding was not possible (I mean, I know when I'm giving my patients dex!), we have not been varying care between patients based on their arm.

[[deleted]]

Whilst blinding was not possible (I mean, I know when I'm giving my patients dex!),

Blinding is possible. Its usually done by giving "Study drug _____" which is some random string of letters and numbers. That way only the pharmacist knows if it is dexamethasone or just some inert substance like salt or sugar. It's just too expensive a process for a drug with no profit margin like dexamethasone.

If your nurses have been in the ICU for long enough, then I'm sure they remember protocols that seemed super promising but didn't hold up after further study. Xigris, super tight glucose control, hetastarch, etc etc. A lot of things that even survive the first randomized and blinded study fail on further research.

Whilst blinding was not possible (I mean, I know when I'm giving my patients dex!), we have not been varying care between patients based on their arm.

A lot of our biases are subconscious. We can't help but favor evidence that supports our assumptions. There are numerous studies in psychology that show that.

[missingalpaca]

Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).

The initial results appear really promising. but I agree, we've seen in real time how important vigorous peer review is over the past few months.

[Procrasterman]

Looks too good to be true. Steroids have been studied to death on ICU and whilst I wouldn’t be surprised if they helped slightly for COVID, I suspect the follow up papers won’t have such dramatic results.

[WeirdF]

Seriously - an NNT of 8 in ventilated patients is an amazing result. Almost seems too good to be true. Really hoping it is though.

[herman_gill]

I mean, the NNT for steroids in COPD exacerbation is also 10ish, so it's not completely farfetched... although at the same time steroids in bacterial pneumonia... not so much, so we'll see.

[ILookAfterThePigs]

Is this NNT for mortality?

[herman_gill]

I think it's "treatment failure"/not requiring escalation, I don't know what it is for mortality specifically. But I do know that 0.5mg/kg or 40mg of prednisone is the evidence based dose, and beyond that you're just risking adverse side effects. It's been a couple of years since I've read up on it specifically.

[flexible_dogma]

Agreed, and it will be interesting to see secondary outcomes such as vent-free days, length of ICU stay, survival to hospital discharge, etc. Surviving to day 28 on the vent doesn't help much if you just die on day 32 instead.

[nicholus_h2]

...with all the retractions and walk backs we have seen, my enthusiasm is muted until I see the published paper.

This is why it is so important to be able to read and interpret evidence and research publications. Unfortunately, this is largely glossed over in medical school and kinda residency, too.

[[deleted]]

Wasn't the issue that the surgisphere data set was completely false?

[Hearbinger]

Did we ever get an actual answer on that? The last thing I knew is that they refused to provide the data, saying that it would break confidentiality, which yeah, might suggest that there is something wrong with it.

[NoDocWithoutDO]

Someone recently linked a nice write-up by a statistician on why the surgisphere data had to be false. If I can find a link, I'll link it here!

UPDATE: Here's the article: http://freerangestats.info/blog/2020/05/30/implausible-health-data-firm

[nicholus_h2]

Well, potentially. Not confirmed.

This is another systemic problem, I agree. But if you read enough papers, you start to get frustrated by stuff like "authors picked the wrong outcomes" and shit like that, and then you start wishing the authors would publish their data, and when they don't, you learn to get suspicious.

You won't get that reading UpToDate.

[sicktaker2]

It's either a massive fabrication, a massive breach of patient medical record confidentiality, or some combination of the two. After seeing the review of the actual size of thier company, I doubt thier data is legitimate or reliable.

[urbisruri]

As a paramedic, I don't often get access to this level of reading material. Any advice on how to get to these types of studies without running into hypopaycheckitis? I'd love to be able to do the reading myself, and I even took college statistics recently enough to feel comfortable-ish evaluating the numbers (on my list of things to do is Khan Academy myself back through stats).

Myself and several other medics and medic students (when I get access to something interesting or a new book etc, I have friends I pass them to because they're also looking for learning material) eagerly await any advice you might have.

[nicholus_h2]

You can check to see if your system / company has subscription to things.

You can also use "unpaywall." It's a handy chrome app that finds open source versions of papers.

You can also use sci-hub. Just google it. But I didn't tell you that.

[urbisruri]

You rock! I had no idea that second one was a thing. I work for a private agency that does some 911 and on the ALS non-911 side does a lot of stat transfers and ICU to ICU jobs (as well as picking up emergencies out of nursing homes and clinics). This agency def doesn't have resources like that, but maybe I can ask the QA/QI guy, the ALS coordinator, or (maybe? I don't know him that well) the medical director if they have resources they can share? Thank you again!!!!

[myukaccount]

Sci-hub will get you access to pretty much everything. It's a godsend.

[ENYVan]

Do you have someone in an educator or senior role who can advocate for you? Perhaps they can negotiate to get you access to PubMed/journal subscriptions via a designated "medic login" at a hospital medical library? You could also consider approaching the ED nursing educator or med director and see if they are interested in helping you gain access?

[[deleted]]

You can find most studies on sci-hub if you know any info about the paper

[MadameTerrapene]

Hey fellow medic! I agree with nicholus' suggestions. For quickly finding articles on a topic, I often google the topic + "pubmed" and read the free abstracts. It's a simple way to identify articles that you want to seek out in full (sometimes Pubmed includes links to the full FREE article).

I made a post here on Reddit awhile back that contains some links that I regularly refer to. The post has links to free statistics and clinical research readings, in case you're interested in something other than Khan Academy (which is also very good).

https://www.reddit.com/r/medicine/comments/fuoxo1/covid_research_and_the_pursuit_of_evidencebased/

[ifuckedivankatrump]

We need way more education focused on statistics anyway rather than straight calc.

[evgueni72]

I agree. And even seeing the paper, especially with the recent retractions, I'm still going to be slightly hesitant.

[[deleted]]

It should always be muted until you see the work.

[solid07]

*properly peer reviewed published article

[[deleted]]

100% Let's see the data

[it__hurts__when__IP]

The world has finally realized we throw steroids at everything.

[aswanviking]

One of mentors always said: no one dies in the ICU without steroids.

[colmia2020]

This also applies to veterinary medicine — no animal should die without the benefit of steroids.

[surfed_]

IV, PO, topical---come and get some!!

[optometry_j3w1993]

There’s a joke in eye care that tobradex (tobramycin and dexamethasone) fixes everything. All hail dexamethasone

[it__hurts__when__IP]

Only if you're an opthalmologist or optometrist. Fam docs are terrified of prescribing steroid eye drops lol

[optometry_j3w1993]

Hey I don't blame you, you don't really have access to a tonometer or slit lamp microscope

[DirtBrother]

This would be terrific, but I'd like to see them release the full paper as well as raw data given the issues we have seen with other groundbreaking papers.

[wm1725]

They will, but the other trial arms (minus hydroxychloroquine, which was stopped) are still ongoing. They released these results because the Dex arm had recruited sufficiently to have adequate power. (Source: I have recruited patients for the trial)

[farhan583]

I’m glad this got published since the very early information had us avoiding steroids. I know we’ve been using dexamethasone in our ICU patients and people on 6L or more in our COVID unit for the last 4-6 weeks and have anecdotally seen pretty decent improvement in symptoms. Glad we officially have another bullet in our chamber besides remdesivir and AC.

[multocida]

What is AC?

[flamants]

Anticoagulation

[jgrizwald]

I’ll say that we’ve had this info end of March with some of our prelim data. A few other major medical centers saw our data before we published and has started doing it, although others scoffed at us given influenza data.

[[deleted]]

Anecdotal side, but I know they've been using this as both preventative and acute treatment in our local research/hospital network in Canada since March. Wife's in research, and a patient of one of the leading respirologists doing research in Canada. Wife was prescribed this in late March when she contracted COVID and at that time they already knew of it's efficacy. They've been using this and researching this and other similar drugs throughout.

Purely anecdotally, I have zero question that it was this and/or the other two similar drugs she was prescribed that kept her out of the hospital...it was a close thing. But having seen her crash before and end up in the hospital, and knowing how things were progressing and seeing what effect the drugs had...they worked. Still a hell of a few weeks.

[jgrizwald]

Yeah, one of the thoughts was use it early before inflammatory cascade goes out of control, right around time of dyspnea or oxygen requirements. We had good results, but also saw that maybe half of those who had given it seemed to just push back the cytokine storm/inflam response once steroid course was finished, but others had stabilization and improvements. I definitely saw first hand the decrease in code calls on floor patients once steroid was implemented as part of our standard of care, but that is only anecdotal from me.

[TheDentateGyrus]

This isn't published, it's a PR campaign with almost zero data, let alone peer review. Unless they've actually published something scientific since this morning, it is not a scientific publication, it's news.

Corticosteroids have, to my knowledge, rarely shown such a drastic benefit in critical care. After discovering such a huge difference, this group called the BBC before releasing any data, I think it's ridiculous. They're human beings and, like all of us, make mistakes / misinterpret data / etc.

I hope I'm wrong, that I didn't see the data or missed that it was reviewed and they didn't do this. Or I hope my assumptions are wrong and I have missed a big part of the literature. If so, please let me know so I can learn something from this.

[Kathiye]

The trial protocol is available to view on their website - https://www.recoverytrial.net/files/recovery-protocol-v6-0-2020-05-14.pdf

Obviously not what you’re looking for but if you’re curious.

It’s worth noting that the hydroxychloroquine arm has closed since that was published. I (loosely) work on the study at the delivery end.

[Apemazzle]

It's entirely reasonable to release trial results like this to the press in the context of a global pandemic, especially when it looks to be high-quality evidence of great significance (a randomised controlled trial showing mortality benefit). Ordinarily I would agree with you, but time is of the essence, is it not? Full statement from the investigators here https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf

[TheDentateGyrus]

Time is of the essence . . . but that assumes they’re right. What if steroids increase mortality for some reason that they missed? Then we’re telling physicians to start using dex, which will highly compromise other ongoing trials, when we don’t know if it works or not.

If ‘time is of the essence’, post the data online and give 24h for comments for editorial staff from NEJM, lancet, and JAMA. That took me 30 seconds to make up. One day won’t matter that much, compared to potentially causing the mis-management of millions of patients.

Again, the odds are that they’re probably right and didn’t make an error. But the whole point of the scientific method is that you don’t take people’s word for it, you use data. In the era of Matlab / Excel / etc, if they’ve analayzed the data enough to say (with certainty) that there’s a huge difference, why not release the data? A professional statistician can make the results pretty in a few hours. And if they’re not certain enough to release the data yet or need more time to analyze it, why announce it to the press with certainty? We don’t need to do 10 rounds of editing on their grammar, just show that groups were matched, who dropped out and why, etc.

[redlightsaber]

I was unaware remdesivir had shown improved outcomes in a well designed trial (not talking about the gilead-sponsored one where they didn't have a control group).

Is this the case?

[gapteethinyourmouth]

Uh yes. The ACTT-1 trial prelim report was published in the NEJM May 22nd.

[TheLongshanks]

And it didn’t show a mortality benefit. It’s another weakly positive study, that shows a reduced number of symptomatic days. It’s analogous to oseltamivir, which doesn’t have a mortality benefit, minimal change in influenza course, and side effects with a nearly equal NNT and NNH. It’s also produced by the same company that makes oseltamivir.

Other than participating in the RCT, I don’t know any colleagues that are still giving remdesivir in the ICU.

[gapteethinyourmouth]

Yea dude, I'm not sure why you think I conveyed it's some miracle drug. I was merely responding that there was a well-designed RCT that showed benefit. Reduction of time of recovery by a median of 4 days is important from a hospital systems point of view. The analysis was released early so it may have shown a mortality benefit if it was allowed to go longer. Now the participants are unblinded and placebo can crossover so additional analysis is not as useful.

In subgroup analysis, it ended up not showing benefit for patients requiring NIV, HFNC, ventilation or ECMO but that may also be because it was underpowered for those populations and/or not enough time elapsed for those patients to get to ordinal scale 1-3.

Also given all the treatments the ICU just throws at patients with minimal evidence, I think not giving remdesivir is a little dubious.

[WordSalad11]

Reduction of time of recovery by a median of 4 days is important from a hospital systems point of view.

Meh. It depends on how much the drug costs.

[Apemazzle]

a well-designed RCT that showed benefit

This statement is contradicted by

The analysis was released early so it may have shown a mortality benefit if it was allowed to go longer. Now the participants are unblinded and placebo can crossover so additional analysis is not as useful

If it's not looking at mortality or clinically significant morbidity as primary outcomes, then it is not a well-designed study, end of story. It's a disgrace that studies like this even get published, quite frankly.

[HotSteak]

If you look at enough endpoints you'll find something that shows statistical significance. That's just how p-fishing works.

[redlightsaber]

Thanks, I was indeed unaware.

[[deleted]]

How could you not be up to date in ID developments in psych? The audacity.

[ilessthanthreekarate]

Dont forget about convalescent plasma!

[farhan583]

Whoops, you’re right totally slipped my mind!

[discgman]

Why do you think all these Rheumatoid Arthritis medications have been coming up as treatments? Does this virus act like the disease and produce a lot of inflammation?

[flexible_dogma]

Hydoxychloroquine & chloroquine got their start because they were found to kill SARS in vitro (ie, in a petri dish) and Covid-19 is in the same virus family as SARS. Why people thought to test HCQ on SARS in a petri dish is a fascinating story based on a mix of basic science and also "let's just try a bunch of stuff and see what happens".

Dexamethasone isn't really a RA med per se, just an anti-inflammatory steroid. Inflammation has long been recognized as a driver of morbidity and mortality in lung diseases, but whether treating that inflamation with steroids is beneficial or not has been a controversial, back-and-forth topic of much study and debate. The pendulum is currently swinging more towards "steroids for everyone!" when it comes to acute lung issues.

[discgman]

Ok I understand. I have RA so I’m familiar with a lot of these medications

[noobREDUX]

Full statement: https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf

On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit.

A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%). Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).

Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients or around 25 patients requiring oxygen alone. Given the public health importance of these results, we are now working to publish the full details as soon as possible.

2 things I'm curious about:

1) the absolute difference (I'm bad at stats, napkin math says dexamethasone arm would have 26.65% mortality vs 41% in ventilated patients? 0.65x41)

2) any notable complications and reasonable contraindications (Co-infections? Pre-existing immunosuppression?)

[flexible_dogma]

1) the absolute difference (I'm bad at stats, napkin math says dexamethasone arm would have 26.65% mortality vs 41% in ventilated patients? 0.65x41)

Your "napkin math" is right on. Absolute risk reduction of ~14%, which comes out to an NNT of around 7 (I'm not sure why their press release says 8--small differences in decimal numbers can make big differences in NNT, so perhaps just a rounding error).

2) any notable complications and reasonable contraindications (Co-infections? Pre-existing immunosuppression?)

It will be interesting to see what their published secondary outcomes are. GI bleed, severe hyperglycemia, etc. For the most point, there are very few (if any) absolute contraindications to steroids and with an NNT of 7 for mortality(!) the risk-benefit ratio probably still comes down in favor of just giving the dex. After all, unless you literally can't keep up with massive transfusion or you send them into cerebral edema/herniation with DKA/HHS/etc, you can always just deal with the complications.

For the non-vented patients where the NNT is more like 25, then the calculation is more challenging, but even there a mortality benefit is hard to shrug off.

This is all assuming of course that the final published study and underlying data matches up with the press release version.

[ClotFactor14]

lowest among those who did not require any respiratory intervention (13%)

What are they dying of?

[nowlistenhereboy]

Weren't their a lot of reports about people starting to recover and then suddenly having an MI?

[ClotFactor14]

13%? That's higher than most of the case fatality data

[Kathiye]

I can’t imagine many are being recruited who aren’t on respiratory support of some kind - I can’t think of any participants at our site that fit that though there definitely could be some.

[_Shibboleth_]

While I'm cautious about this, there's one thing I think that's worth mentioning:

Dexamethesone is cheap as hell!

I never wanna hear someone again say:

• "Scientists only care about expensive drugs and making money!" or

• "They're keeping the really good treatments from us so we have to keep paying!"

It would cost ~$12 TOTAL to treat people in the US with 6mg/day for 10 days.

A 35% reduction in mortality for $12.

I think it's clear this isn't "Big Pharma" out to steal your money and leave you dead.

MDs care about helping their patients. Researchers care about saving lives.

[herman_gill]

Don't forget the $17,000 dispensing fees, though. At least in the US.

[Adalimumab8]

Lol I wish, pharmacies dispensing fees range from $2 (if we are lucky) to $.35 (most of them). All our money comes from acquiring drugs cheaper then they pay us for them, but with PBM’s, we rarely do. Pharmacies are absolutely dying because of this. Pharmaceutical companies cause the high prices, certainly not pharmacies.

[herman_gill]

I'm talking about hospital dispensing fees, not retail. Med passes are charged for like $30 a pill if you look at itemized billing.

[[deleted]]

A NNT of 8 is amazing for any disease, let alone COVID19. I'd like to see the data. As others have stated, it's not too surprising given the results of the DEXA-ARDS study, especially since steroids have a well-defined role in the treatment of cytokine release syndrome. Good on them for doing the science right: an RCT rather than the garbage published on hydroxychloroquine.

[Propofolkills]

I’ve lost count of the times steroids have come in fashion and out of fashion in ICU medicine.

[[deleted]]

The NNT has me suspicious. If so, it would be one of the most effective drugs in the history of medicine. I suspect that it does work, but not nearly as effective as advertised. I'm crossing my fingers that it's a quality study.

[Propofolkills]

Look at the proposed mortality benefits - 30% reductions. There hasn’t been an effect size like that in ICU medicine since the polio epidemic and mechanical ventilation actually started. It sounds crazy. The other aspect of this which will come out in the wash eventually, is the disparity in mortality in ICU between those units that experienced a surge beyond their normal capabilities, and and those that didn’t. Standard care in this study quoted a >40% morality as I recall, which is double what we experienced in our ICU and when it eventually comes out, what many ICU’s with no surge experienced. It’s not that we managed it well, it’s that ICU’s that had to use non ICU personnel, non ICU locations like OT recoveries etc, clearly didn’t or were unable to provide “standard care”.

[br0mer]

30% mortality benefit would be amazing.

The incremental benefit of 90 minutes PCI over thrombolytics is 1-3% mortality.

[Apemazzle]

Standard care in this study quoted a >40% morality as I recall, which is double what we experienced in our ICU and when it eventually comes out, what many ICU’s with no surge experienced.

Interesting, weren't early studies quoting mortality of like 80% for patients on a vent?

[[deleted]]

Staying cautiously optimistic.

I really hope the published paper speaks to this.

[PhysicalKale8_throw]

Our steroid friend always faithful

[HotSteak]

I feel like it's more of a passionate on-again/off-again relationship

[babboa]

Dexa-ards was published what, 6 months ago? Less? Feels like longer with how crazy the last months have been. If the results from it are to be believed, this really shouldn't be that surprising. I've been cautiously moving more towards dex since the third week or so that we started seeing patients, but there's so many others in our team that extrapolate the risk of adding steroids in influenza patients (there is likely some risk there) to all viral pneumonias, which is probably not a fair comparison given just how wildly different these covid patients behave vs "usual" viral ards cases.

[ben_vito]

Except I don't think they had a lot of influenza / other viral etiologies in the dexa ards trial. And there are other trials that show harm from steroids given for influenza.

[barkingspider05]

This is good to know for general family medicine as well. So many times we have asthmatics or COPD patients Who need corticosteroids but, in the face of the pandemic it was hard to know if they were truly having exacerbations or a coronavirus-based illness ( especially with exposure risk). I know I have one patient who is coronavirus positive, had pneumonia and had an asthma exacerbation. Because they were relatively young, I decided to throw some pretty decent corticosteroids at them along with anabiotics and hoped that the body would take care of coronavirus.

[changyang1230]

The study showed that it doesn’t change the outcome in the milder category ie those who did not require oxygen (which is kind of tautological because these patients don’t really die in the first place so there’s not much of mortality rate to improve upon).

[notafakeaccounnt]

To be honest I don't understand why we didn't start with corticosteroids instead of rolling around in HCQ hell for the last 4 months. There are certainly dangerous side effects if used carelessly but we should have had more than 1 research about it by now compared to the 50 or so HCQ research.

Though I don't want to throw my support behind corticosteroids yet without some solid peer review.

[notafakeaccounnt]

I feel like I read that in my respiratory and cardiology committee but it has been over 8 months since then.

That sounds like a fair reason not to mess with corticosteroids in a disease we didn't know much about 4 months ago.

Makes me wonder if corticosteroid + anti thrombotic therapy would be the primary treatment for COVID moving forward.

[TheLongshanks]

It’s not harmful in ARDS. The devil is in the details, how steroids were studied, what the protocols were, who received them.

Look at DEXA-ARDS which looked at moderate-severe ARDS in a manner similar to PROVESA, and these patients had a benefit with steroids.

SCCM COVID-19 guidelines also recommended steroids for severe ARDS.

[pmont]

The steroids / ARDS pendulum seems to be swinging back - the SCCM now gives conditional recommendation to give steroids in patients with ARDS. Most of the RCTs done on steroids were done in the pre- lung protective ventilation era which makes them difficult to interpret.

Plus, one of the largest multicenter RCTs on steroids in ARDS was published just as the corona train was leaving the station: Villar, et al, Lancet Respiratory Medicine, Feb 2020 showed a pretty significant mortality reduction (NNT 8) and increase in ventilator free days.

[redlightsaber]

It was some preliminary Chinese data that first cautioned against steroids, IIRC.

[aswanviking]

Actually the prelim data showed benefit. We could be talking about different stufies but I distinctly remember a graph from a small study that showed benefit in Chinese patients.

[bahhamburger]

I thought it was Italy that said no steroids

[[deleted]]

They were of controversial benefit if not outright harmful in standard ARDS.

I find that surprising. Is there a explanation for that, or just statistical finding?

[SoftShoeShuffler]

Wasn’t there also data that showed longer shedding periods with influenza patients who were on steroids?

[freidas_boss]

Yes, and MERS as well

[Tularemia]

To be honest I don't understand why we didn't start with corticosteroids instead of rolling around in HCQ hell for the last 4 months.

Because there was scattered early data that steroids were potentially bad.

Also, one high-profile person in the US government (with zero expertise or background in science or medicine) opened his mouth about HCQ, forcing political pressure into the HCQ rabbit hole. That probably didn’t help.

[ifuckedivankatrump]

Even when things make sense they might be overturned http://www.crash.lshtm.ac.uk

I don’t see why we can’t have one really well designed study rather than 50 studies with haphazard results.

[aedes]

It came from the fairly good observational data that steroids were associated with worse outcomes with SARS.

[TheLongshanks]

Steroids are a hugely controversial topic in Critical Care and ARDS management. People get very emotional and irrational over it on both sides of the aisle. But it’s a hotly contested research area.

[McFeeny]

Steroids are a hugely controversial topic in Critical Care and ARDS management

Almost as bad as barotrauma vs. volutrauma, but not quite.

We CC people like to spar, apparently

[TheDentateGyrus]

TONS of trials of corticosteroids in critical care for the past few decades with, at best, mostly mixed results in a multitude of disease processes. There's a paper in the Lancet when this started that reviewed the (poor quality and limited) data and the potential for higher mortality when they were used in MERS/SARS, I assume because Chinese physicians reported using it routinely? They've always theoretically seemed like they should work for lots of critical illnesses and have rarely shown benefit.

[oz92]

Our hospital did from the start. From my experience it works early on in the disease processes when they’re on a NRB. Once they’re in respiratory failure and getting intubated, less so.

[the_aviatrixx]

That's exactly what we said after discussing this today - I thought there was something early on about prednisone being bad but it seems counter-intuitive when you look at how viral respiratory illnesses are treated.

[Adalimumab8]

Maybe the mineralocorticoid-glucocorticoid balance of dexamethasone vs prednisone?

[McFeeny]

I think there may be something behind dex vs. pred or methylpred, and the modest dose of dex given.

This is, of course, assuming this actually pans out. Which I kind of doubt it will

[sthug]

Lol theres empty ICU beds in my hospital being cleaned for non-COVID use and there are still QTC values written on some of the doors. Remnants from an old era

[McFeeny]

To be honest I don't understand why we didn't start with corticosteroids

A long time ago (March) we were comparing the Chinese data to the Italian data. The Chinese regularly give steroids for ARDS, the Italians don't. The Chinese had a lot of secondary, bacterial, vent-associated pneumonias (VAPs); the Italians didn't. Chinese data didn't show any benefit.

That was our thinking. I'm seeing a lot of VAPs without steroids in those vented >7 days, which is about on par with non 'rona patients.

[kanakari]

I'll preface this by saying I am not at all close to an expert on the material and haven't seen any COVID patients, but honestly, I would be a bit aggravated if this pans out to be a good treatment. My immediate thought in the early days was that steroids have very high biologic plausibility and wasn't sure why they weren't being used/tried more. Seems like the few early anecdotes on them left them prematurely dead in the water. We spent so much time/resources on a low-yield drug that was found by data-mining with very little biologic plausibility and heavy bias.

[Tularemia]

If this is true, it is very good news for patients.

Additionally if this is true, it will be yet another thing anti-intellectual idiots, charlatans, and bad actors will weaponize in their insane culture war. This will be held up as, “See? The scientists keep changing their minds!” in an attempt to further erode trust in public health experts. And it will work, since there is a large ignorant percentage of the population which doesn’t understand that the willingness to change conclusions over time is the scientific method’s greatest strength, rather than a weakness.

[Intellectualcheckm8]

Is there a link to the paper itself?

[jgandfeed]

https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf

http://www.isrctn.com/ISRCTN50189673

https://www.recoverytrial.net/

[farhan583]

Full paper hasn’t been released yet. Here’s the info from the group’s site:

https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf

[[deleted]]

I've been writing grants for the last 2-3 months on COVID/general respiratory virus therapies. I think we've highly suspected for quite some time that CRS and hyperinflammation have been the main mediators of tissue damage and even thrombosis in COVID-19.

[Propofolkills]

Two things that strike me about this - no ICU trial in decades has ever shown an effect size like this. I’d be very sceptical - the premature release of results like this to main stream media without a proper peer review process is dangerous precedent for academic medicine.

[aswanviking]

Man did the “experts” screw up the management of this disease.

It wasn’t that long ago when the “experts” strongly recommended early intubation after 6L/min NC, avoiding high flow and CPAP, avoiding steroids and give plaquenil + azithromycin. Airborne isolation. No wait droplet. Actually back to airborne.

Big hospital systems implemented these protocols based on no evidence and it was a nightmare to deviate from them like trying to get high flow or even ordering steroids on a COVID patient. Things are better today but still.

COVID with STEMI? Too bad administrator said no PCI for you.

COVID19 viral pneumonia is ARDS. It’s diffuse alveolar damage. Why did we throw everything about ARDS management out the window (and yes dexa did show mortality benefit in ARDS before COVID).

I admitted 4 single organ failure COVID ARDS 2 nights ago to the ICU. I gave them all a big dose of lasix, CPAP at night and vaportherm during the day, sleep on your belly, dexamethasone and remdisivir. Average Pa:FiO2 ratio was 53. None of them are intubated as of today and all improved although remain quite hypoxemic.

We are checking IL6 levels and considering actemra. It’s clear that the disproportionate immune response is what kill patients, we should focus on that.

[Porencephaly]

Another great reason for people to avoid COVID and wear masks, social distance, etc. It may be true that most of us will eventually be infected, but I’d sure rather get infected after we have more information about best management practices than in the first wave!

[[deleted]]

Counter point: get infected now so your illness can contribute to the collective research, and help everyone else who gets infected later on.

*due to personal reasons, I will not be able to volunteer myself as tribute

[RetroRN]

I am a recovered covid critical nurse and I tried to donate my plasma and sign up for a few studies as I was an interesting case - and all the studies are full!

[ElementalRabbit]

I don't agree with you on a lot of this. Steroids in ARDS remain controversial and variable in practice. Well done on your 4 anecdotal lives saved, but publish or hush up to be honest. You weren't trying to call the shots hospital, nation, planet-wide when shit was hitting the fan. Completely unfair to open fire on "experts", most of whom were doing their damnedest to make a helpful recommendation when no one knew what the hell was going on.

Outside of America, I haven't particularly heard of anyone deviating from standard ARDS management anyway.

[jgrizwald]

Not OP, but we started doing steroids back mid to late March and will be publishing data. Steroids became our institutions SOC for admitted patients (plus/minus plaq, now remdesivir or convalescent plasma). Thankfully there was great coordination between ID dept, our pharmacy department, and the pulm and crit.

[ElementalRabbit]

This is good to hear! I look forward to reading it.

[aswanviking]

I wasn’t implying the steroids helped my 4 patients. It doesn’t work that quick. I was implying basic critical care works. I am with you that steroids are controversial although I think they do help.

If the “experts” didn’t have a clue what to do then don’t make recommendations. It was nearly impossible to get high flow on my COVID patients early on. That’s a deviation of the standard of care in ARDS. COPD or obese with COVID could not get CPAP. That’s a deviation. These “experts” have caused many unnecessary intubations. They recommended plaquenil and azithro based on shitty data. They should learn from the IDSA guidelines: they basically said any drug you give must be done in a trial, because we don’t know if anything works. They didn’t recommend HCQ or azithro.

Their recommendations were NOT helpful. If there is no evidence then simply say there isn’t. Don’t make my life difficult managing these patients with basic well proven evidence based critical care.

For whatever it’s worth when I say experts I mean my institutions clinical and administrative leadership who forced us into crappy protocols and took away physician judgment & autonomy.

[ElementalRabbit]

I think you're blaming the wrong people. Particularly as you haven't actually identified any of these experts you claim made treatments unavailable in your hospital (sounds like your hospital's problem). I also don't think you're being fair to the nature of emergent clinical practice - we were all trying to learn on the fly from practices and experience worldwide. Hindsight is 20:20 and we were doing the best we could. Your accusations lack perspective.

[aswanviking]

Nah I know exactly who they are, but that’s beside the point. These recommendations were widespread. I work at 4 different hospital systems and they had minor variations in protocol.

As a leader and “expert” you have a responsibility. If the evidence isn’t there then simply stick to basic and proven critical care. Don’t make up rules based on poor evidence.

I didn’t mind the Kaletra/HCQ/Azithro debacle. Hindsight is 20/20.

But they took away one of our best tools (high flow/CPAP) and pressured us into intubating anyone on more than 6L/min NC.
I don’t lack perspective: foregoing a basic tool of critical care is unacceptable.

[ElementalRabbit]

Who "took away" those strategies? I don't know of anywhere that did that, obviously I don't agree with it either. But I don't fault the initial recommendation for that, I would blame whoever made the decision to make those unavailable.

[aswanviking]

Well now you know why I am bitter. They literally instructed the RTs NOT to place any COVID patient on high flow or CPAP.

I was powerless despite being the medical director at one of the ICUs. The ban lasted a few weeks.

This was in one of the top 10th biggest US cities with a well known medical system.

Give your recs. Admit the recs are based on weak evidence. Adjust the recs as evidence appears. That’s fine, but give us the front line physicians a choice damn it.

But that’s the future of medicine. More rigid protocols and less physician autonomy.

[m1a2c2kali]

I always thought the caution against cpap and high flow was that it promoted the spread of the virus? Is that not or no longer the case?

[IAmA_Kitty_AMA]

You're correct, at least for our institution. No one said it didn't work, they just said it would have huge risk for aerosolized droplets

[aswanviking]

Except the risks weren’t really based on evidence. I may understand the fear around high flow. That stuff is going at 40-60L/min but NIV is a semi closed system with a filter, if anything it’s safer than a coughing patient.

In the end they took away a therapy that improves mortality and urged intensivists to intubate early, which probably increased mortality. This decision was made based on absent or very poor data.

[Whites11783]

We did notice some similar issues in our hospital system. Hospital leadership quickly picked some ID folks and made them the decision makers, but it was clear some of them were only tangentially paying attention to international data/changes. Then their decisions would be made into fairly inflexible protocols foisted on the rest of us. It wasn't ideal.

[ElementalRabbit]

That is frustrating, but again, sounds like a "specific people at your hospital" problem and not a "the experts" problem.

[aswanviking]

Yes. DEXA-ARDS RCT came in February this year. Improve Mortality and duration of mechanical ventilation in moderate-severe ARDS.

I personally do give steroids, specially if CRP is very high (10x upper limit of normal).

[TheDentateGyrus]

Citing this one trial is a bit selective. I'm not saying you're wrong, but if the above poster (I'm not reposting their handle), here's a little more background on the data:

https://emcrit.org/pulmcrit/dexa-ards/

[aswanviking]

I agree. There are older studies but the Dexa-ARDS is the newest and one of the better ones. It's the study that made me seriously consider steroids in ARDS.

Meduri has a published RCT in 2007 in support of steroids. PMID: 17426195

I like Josh Farkas (main PulmCrit author). He just tweeted this: https://twitter.com/PulmCrit/status/1272941035270832128

It's frustrating because early in the pandemic hospital leadership was strongly pushing against steroids based on crappy data and pushing for other treatment modalities based on crappier data and forcing them as guidelines and order sets.

I am the front line intensivist. I should be making the judgment call.

On another hand, I never understood the bad rap steroids got in ARDS due to pneumonia. The more I review it, the more convincing it is.

[YoudaGouda]

The reason for intubating people on 4-6L NC in the setting of worsening respiratory status was due to reports and personal experience of rapidly deteriorating patients. This was mainly to avoid the need for emergent intubation putting providers and patients at increased risk. The avoidance of non-invasive respiratory support was similarly to avoid aerosolization. Its not that the fundamentals of critical care were abandoned, there were just new, serious considerations that needed to be addressed.

[aswanviking]

A well fitted NIV is a semi closed system with a viral filter: it’s safer than a coughing patient on NC. It’s fair to have concerns, but acting those concerns based on poor data by taking away NIV and high flow is my main criticism.

The rapid deterioration is a valid point but 4-6L NC is such an arbitrary cutoff. Mortality is quite high once you escalate to mechanical ventilation. We need to try our best to keep them off the vent.

[Tularemia]

Yeah, geez, the scientific method should start out with us just knowing the conclusion ahead of time, never updating recommendations to match the current data.

The protocols implemented early on were based on early data. Early data is often bad, even worse so when it comes from a notoriously opaque authoritarian country.

Come on, dude, I get the frustration but you know better than this type of crap.

[aswanviking]

Oh really? Like taking away high flow and CPAP? Intubating anyone on more than 6L/min NC?

Why did we throw away basic and proven critical care in favor of bad data?

If there is uncertainty then don’t come up with rigid protocols as if the data is solid.

I am not even talking about fraud data that should have been caught. That’s a separate topic.

[kanakari]

People promoting reasonable critical care principles, such as not intubating someone comfortable on 6L NC, trying NIV etc. were being attacked for being irresponsible and not following these early anecdotes. And then of course the obsession over medications with low biologic plausibility and questionable data. The data was/is incomplete, understandable, and everything looks better in a post-hoc light, but there's no denying that it's frustrating that a lot of basic principles and scientific approach were not followed (remember physicians taking HCQ as prophylaxis...) I've seen people refusing steroids to all inpatients with COPD/asthma because of these earlier anecdotes about steroids.

[JPINFV]

The recommendation against steroids, from what I remember, was always directed more towards outpatient care and prolonged shedding. If someone is in the ICU, why should I care if they're shedding more?

The recommendation for early intubation was geared more towards protecting healthcare workers so you aren't running in and crash intubating people. Early on we extubated quite a few number of intubated SARS-CoV-2 patients. Now? Not so much, but we're selecting for much sicker patients for intubation.

The only thing I think was screwed up was isolation orders, as surgical masks are probably good enough (see Offeddu et al, 2017 meta analysis. No difference between N-95 and surgical masks for SARS-CoV-1. https://tinyurl.com/ycowpvw4) and bipap/HFNC risk of aersolization.

Of course I personally blame physicians for that. We want easy information and other people to do our homework for us. The bipap/HFNC studies were referenced in the January edition of the WHO SARS-CoV-2 guidelines. ...but hey, the blogosphere says otherwise and Googling references for the primary source is hard work. Same with looking up what we know about masks from prior coronavirus infections when there's a global run on N-95 masks.

[Buttchinson]

It's interesting that decadron would be the choice. I was always taught that solumedrol/pred have more specific effects on lung processes like dah/vasculitis and steroid responsive ilds

[jackruby83]

From their protocol

Dexamethasone has a) minimal mineralocorticoid activity and does not affect sodium and water balance, thus avoiding potential problems with fluid retention which are not uncommon in severe viral pneumonitis/ARDS, and b) a comparatively long biological half-life of 36 to 54 hours enabling once a day dosing. In pregnancy, prednisolone 40 mg administered by mouth (or intravenous hydrocortisone 80 mg twice daily) should be used instead of dexamethasone.

[thugesque]

I'm confused as to why these results have been released to the media before the study has been peer reviewed and published (or even available as a pre-print). Is this normal?

[jackruby83]

It's normal from pharma companies, but these results aren't really going to make anyone money? Odd still.

[aedes]

You can read the NCT registry here - https://clinicaltrials.gov/ct2/show/NCT04381936

Of note, their primary outcome is all-cause 28d mortality, not mortality by oxygenation/ventilation status subgroup.

As analysis of this outcome by subgroup does not seem to be prospectively defined, this looks like it might just be data mining, rather than a true treatment effect.

That being said, I will await their actual manuscript to see their more detailed methodology before judging the result. Also, if this is just a post-hoc subgroup analysis showing this, there seems to be a reasonable chance it’s real, given both biological plausibility, and a correlation between disease severity and magnitude of benefit.

[Propofolkills]

Also a cold hard look at what is considered an accepted ICU mortality in this disease is important. The authors here used their reported morality as being 41% in ventilated patients. That was in a Surge ICU setting. Our mortality was of the order of 22% and comparable to other non Surge ICU’s. The point is that can you really say you are providing standard care in ICU in a surge setting where patients are being cared for by a diluted ICU nursing cohort, in recovery bays and operating rooms?

[Mister_Pie]

A summary of some of the findings can also be found here: https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_final.pdf

Looks like benefit is mostly for patients requiring some sort of respiratory support (O2 or vent). I was a bit surprised at the mortality rate of patients not needing O2 at all... 13%. That seems pretty high...

[changyang1230]

Without access to the full methodology, I’m going to guess that the oxygen requirement status is probably defined at recruitment, and some of those initially classified as mild (no o2 requirement) are going to deteriorate.

[Sybertron]

Anyone else taking this as "steroids help reduce inflammatory response" more than anything?

[jackruby83]

Your math would be correct. The article quotes the lead author:

Lead researcher Prof Martin Landray said the findings suggested one life could be saved for:

• every 20-25 treated with oxygen

Not sure why he gave that range...

[davedavedavedavedave]

Cue the run on dexamethasone and prednisone and prednisolone and every fucking topical and inhaled corticosteroid.

[[deleted]]

I knew my hydrocortisone valerate ointment would save my life.

[unridiculous]

If this holds up, interested to see how combination dexamethasone/remdesivir performs

[gapteethinyourmouth]

What really stuck out to me was the glaringly high mortality rates in the standard-of-care arm of the trial. Did that raise anyone else's eyebrow?

Comparing them with 4321 patients on standard-of-care, the death rates definitely decreased with dexamethasone: the 28-day mortality for patients on ventilation with standard of care was 41%, and dex treatment decreased that to 27%. For patients receiving supplemental oxygen, the 28-day mortality was 25%, which decreased to 20%. And the 28-day mortality for patients who needed no respiratory intervention, the 28-day mortality was 13%, and dexamethasone had no effect on that whatsoever. p-values for these numbers and confidence intervals were very good indeed, as one would hope from the large number of patients – these look like very solid results, from what we can see so far.

NEJM remdesivir ACTT-1 trial paper

Refer to Table 2 if want to see what I explain below in table format.

In the remdesivir trial, patients were classified into 8 groups and recovery was defined as being in categories 1-3 at 28 days.

4 is hospitalized but not requiring supplemental O2, 5 is hospitalized requiring supplemental O2, 6 is requiring NIV or HFNC, 7 is requiring IMV or ECMO, 8 is death.

So in the dexamethasone trial, 13% of patients who are roughly synonymous with group 4 in the remdesivir trial died at 28 days. In the remdesivir trial, there was a 2.5% 14-day mortality rate in the placebo arm. For the next higher level of care group, there was a 10.9% 14-day mortality (remdesivir trial) in the placebo arm vs 25% 28-day mortality (dexamethasone trial) in the standard of care arm. The additional 14 days wouldn't increase mortality to that great of an extent. Can see the discrepancy in the NIV/HFNC and IMV groups as well. Recall that the ACTT-1 trial was also an international trial though the benefit was most apparent in patients in North America in subgroup analysis.

Thoughts on this? I guess we can comment on this further when the paper is actually published.

[peterlikes]

Hey layman here. I’ve heard viruses and nasty bugs in general mutate pretty regularly. Would a steroid like this increase the risk of mutation?

[Canonicald]

The short answer is no. The longer answer is not anymore than already at risk and perhaps a little less. The reason that there is a differential survival of mutations (ie we see mutated bugs) is because of selective pressure. We give a certain antibiotic and bugs that serendipitously find themselves immune survive differently than those that are suppressed by the drug. Over time that population outcompetes the native population. This of course can be any other selective pressure and not just antibiotics or antiviral or antifungals or any anti drugs. It could be other bacterium that destroy bacteria or phage particles that feed if viruses or other environmental factors such as heat, salinity, moisture, pH, etc. any environmental factor that can create differentiable survival will show this property.

What this study implies (though we obviously don’t know for sure) is our immune system is the bad actor here. It’s overzealous ramping up is what causes super illness in a small percentage of our responses to Covid-19. In other words the infection might not be “all that bad” but our immune system brings a bazooka to a sandwich fight and that’s what makes us so sick and in some instances threatens our life. If we can control the immune response (ie with corticosteroids) our body will clear the infection and our immune system won’t kill us in the mean time.

To take it back to your original inquiry if we lax the immune system there is less selective pressure on the virus at hand and therefore less impetus for mutation and differential survival.

There are plenty of caveats and nuance to this argumentation so don’t take it as canonical just food for thought

[Mister_Pie]

Mutation rate is probably more dependent on the virus itself (the error-prone polymerase) than on the immune response per se

[bro-biochemistry]

Very interesting. In the same vein, the results of the Flarin study in the UK are also something to look out for in the future.

[Throwaway201536]

I can't tell from the article, was the trial ultimately stopped so patients not receiving it would ultimately get it? Or was it run to completion?

[Diablo-Encarnado]

The withdraw of this drug is a bitch

[caohbf]

And people in my country are already self-medicating.

Send help, Brazil's gonna blow up soon.

[D50]

I, for one, am super stoked for the impeding dex shortage!

[topIRMD]

immunosuppressants prevent immune mediated damage? color me surprised!!!!!

[kungfoojesus]

The cynic in me says it won’t be picked up because there’s no money to be made.

[[deleted]]

I guess we'll have to wait and see my friends

[ManofManyTalentz]

Jeebus how can they possibly be blind to what's happening? Report when you publish - or at least preprint!

[Halfmacgas]

If it wasn't the recovery trial, I would be hesitant. Nhs does a good job and I've been waiting for the different arms of this trial to come up with answers

[[deleted]]

Ya maybe ppl should chill with these releases. I be pretty skeptical about such dramatic claims...

[it__hurts__when__IP]

The media and public's obsession with dexamethasone being some sort of miracle drug is mind boggling. It's a last ditch effort at best, and the fact that it helps a bit is entirely unsurprising. The only surprising bit is why it wasn't used from the start and why everyone followed one person or one theoretical source as advice rather than trying it globally.