ADDENDUM 1/5/22: We have now been using dexamethasone for COVID-19 patients who require oxygen since summer of 2020. We have been mostly stuck on using the dose of 6mg per day in these patients simply because that’s what the great authors of the RECOVERY trial group did. This isn’t a dig at them, they did a fantastic job scurrying together a clinical trial that provided a positive mortality outcome. But rather the 6mg of dexamethasone for everyone, from 45kg little old lady to the 150kg patient across the board never sat well with me. Now, there is data that using double that dose, 12mg, shows a probability “of benefit on days alive without life support and days alive out of hospital”. The paper is linked immediately below. Sorry this page is a hodgepodge of steroid in COVID-related articles.

Granholm A, Munch MW, Myatra SN, Vijayaraghavan BKT, Cronhjort M, Wahlin RR, Jakob SM, Cioccari L, Kjær MN, Vesterlund GK, Meyhoff TS, Helleberg M, Møller MH, Benfield T, Venkatesh B, Hammond NE, Micallef S, Bassi A, John O, Jha V, Kristiansen KT, Ulrik CS, Jørgensen VL, Smitt M, Bestle MH, Andreasen AS, Poulsen LM, Rasmussen BS, Brøchner AC, Strøm T, Møller A, Khan MS, Padmanaban A, Divatia JV, Saseedharan S, Borawake K, Kapadia F, Dixit S, Chawla R, Shukla U, Amin P, Chew MS, Wamberg CA, Gluud C, Lange T, Perner A. Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial. Intensive Care Med. 2022 Jan;48(1):45-55. doi: 10.1007/s00134-021-06573-1. Epub 2021 Nov 10. PMID: 34757439; PMCID: PMC8579417.
Link to Article
Link to FULL FREE PDF

COVID STEROID 2 Trial Group, Munch MW, Myatra SN, Vijayaraghavan BKT, Saseedharan S, Benfield T, Wahlin RR, Rasmussen BS, Andreasen AS, Poulsen LM, Cioccari L, Khan MS, Kapadia F, Divatia JV, Brøchner AC, Bestle MH, Helleberg M, Michelsen J, Padmanaban A, Bose N, Møller A, Borawake K, Kristiansen KT, Shukla U, Chew MS, Dixit S, Ulrik CS, Amin PR, Chawla R, Wamberg CA, Shah MS, Darfelt IS, Jørgensen VL, Smitt M, Granholm A, Kjær MN, Møller MH, Meyhoff TS, Vesterlund GK, Hammond NE, Micallef S, Bassi A, John O, Jha A, Cronhjort M, Jakob SM, Gluud C, Lange T, Kadam V, Marcussen KV, Hollenberg J, Hedman A, Nielsen H, Schjørring OL, Jensen MQ, Leistner JW, Jonassen TB, Kristensen CM, Clapp EC, Hjortsø CJS, Jensen TS, Halstad LS, Bak ERB, Zaabalawi R, Metcalf-Clausen M, Abdi S, Hatley EV, Aksnes TS, Gleipner-Andersen E, Alarcón AF, Yamin G, Heymowski A, Berggren A, La Cour K, Weihe S, Pind AH, Engstrøm J, Jha V, Venkatesh B, Perner A. Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial. JAMA. 2021 Oct 21. doi: 10.1001/jama.2021.18295. Epub ahead of print. PMID: 34673895.
Link to Article AND FULL FREE PDF

Article shared on IG on 6/18/21 on Methylprednisolone
Ranjbar K, Moghadami M, Mirahmadizadeh A, Fallahi MJ, Khaloo V, Shahriarirad R, Erfani A, Khodamoradi Z, Gholampoor Saadi MH. Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis. 2021 Apr 10;21(1):337. doi: 10.1186/s12879-021-06045-3. Erratum in: BMC Infect Dis. 2021 May 11;21(1):436. PMID: 33838657; PMCID: PMC8035859.
Link to Article
Link to FULL FREE PDF

CLICK HERE to learn why I use methylprednisolone rather than dexamethasone in my COVID patients.

Article shared on IG on 7/13/21 on Secondary Infections
Ritter LA, Britton N, Heil EL, Teeter WA, Murthi SB, Chow JH, Ricotta E, Chertow DS, Grazioli A, Levine AR. The Impact of Corticosteroids on Secondary Infection and Mortality in Critically Ill COVID-19 Patients. J Intensive Care Med. 2021 Jul 12:8850666211032175. doi: 10.1177/08850666211032175. Epub ahead of print. PMID: 34247526.
Link to Article
Link to FULL FREE PDF

RECOVERY TRIAL

We are much in need of some good news. It appears that we have a little bit of good news regarding providing our COVID patients with dexamethasone. You all know that I like inexpensive and readily available medications. We need to remember that, even though most of us are in (relatively) resource rich USA, the rest of the world has to battle this virus as well. The full paper has not been published yet. My plan is to update you all when that occurs. This study will go by the name the “RECOVERY trial” which stands for Randomised Evaluation of COVid-19 thERapY.

Design: investigator -initiated, individually randomized, controlled, open label, adaptive trial. The reason I believe they did this was to be able to do trials on several different treatments simultaneously.

Number of patients:

2104 received dexamethasone
4321 were randomized to usual care. Hopefully the paper will tell us what usual care is.

Patients also received azithromycin (23-24%).

Dexamethasone in COVID dose:

6mg (PO or IV) daily for 10 days

Outcomes when providing Dexamethasone in COVID

Primary outcome: all-cause mortality within 28 days of randomization
Mechanical Ventilation Patients: reduced deaths by 35%
Patients receiving supplemental oxygen: reduced deaths by 20%
Patients on room air: no benefit. Perhaps even a trend to harm. Funny that the pre-print version said “possible harm”.

Number needed to treat (NNT) to prevent one death:
If on mechanical ventilation: 8
If on supplemental oxygen: 25
(and 7% of patients in the usual care group received dexamethasone)

The “benefit was clearer in patients treated more than 7 days after treatment onset”. I believe they meant to say “symptom onset”.

Other outcomes:
Discharge from hospital 1 day sooner. (12d vs. 13d median)
24% decrease risk of intubation if receiving dexamethasone and not intubated. (p=0.021)
Receipt of hemodialysis or hemofiltration
Major cardiac arrhythmia
Receipt and duration of ventilation

Data that we can tease out

28 mortality with usual care
– if on mechanical ventilation: 41%
– if only requiring oxygen: 25%
– patient not needing oxygen: 13%

What we don’t know (this can be skipped now that we have these data).

Obviously, there’s no information about demographics of these patients, what hospital day the dexamethasone was initiated, adverse effects (of which I do not expect many outside of hyperglycemia). We need to wait for the final paper to be published but I am thrilled they gave this to us.

Does it hinder/arrest the progression from needing supplemental O2 to going onto a ventilator? I’d like to know how many patients were started on dexamethasone while on the ventilator.

Addendum on 8/2/2020

This paper has been out for a few days now. It was published on July 17th. Today is 8/2/2020. To date, this is the only treatment we have that decreases mortality.

Important points to tease out: 26% of patients who go into the hospital in the UK with COVID die. 37% of patients who are intubated with COVID die.

Methods: controlled, open-label trial. The RECOVERY group (176 hospitals in this team) in the UK was conducting a series of trials simultaneously. Patients were randomly assigned to receive 6mg daily of dexamethasone or usual care. Patient distribution was a 2:1 ratio of usual care vs. dexamethasone. They were recruited after the first week of their illness.
2104 patients received dexamethasone and 6425 received usual care.
16% of these patients were on the vent or ECMO
60% of these patients were on supplemental O2
This means that 24% were on room air. What were they doing in the hospital on room air? I digress.

What is usual care?
Azithromycin was received in both groups equally. We’re not using this in our practice in the US at this time.
<3% of patients got the miscellaneous stuff that has shown no benefit, hydroxychloroquine, Kaletra (lopinavir-ritonavir) or IL-6 antagonists (which recently showed no benefits, I did a podcast on that). Less than 3% of patients in both groups got these therapies.
Remdesivir wasn’t really around at the time of this trial, for those asking.

These patients were followed up for a max of 28 days.
The median duration of treatment was 7 days, meaning that not all of them got the 10 day course.
8% of the patients in the usual care group were getting dexamethasone, this makes it harder to show a mortality difference but alas, we still saw it.

Comparing the two groups: the dexamethasone group was on average 1.1 year older than the control group.

Primary outcome: all-cause mortality at 28 days after randomization. I love that these authors swung for the fences here. We shall be receiving more data in 6 months for other outcomes, hence this being a “Preliminary Report”. They found that mortality at 28 days was significantly lower. It decreases the risk of mortality by 17%.

All in all, the NNT to treat to save one life in all comers, patients on ECMO, vent, supplemental O2 or room air is 35.7. That’s not too exciting.

In patients who are on the vent, however, it is more promising. There is a 36% decreased risk of mortality in those patients. The NNT to save one life is 8.3. Please take into account that this is NO CURE. 8 patients still die to save one. The mortality rate of patients on the ventilator is still 29.3% even with dexamethasone. It was 41.4% without dexamethasone.

In patients who are not on the vent but are on supplemental oxygen, they had a decreased risk of death of 18%. The NNT in this population is 34.5. That is again pretty high. Good thing that dexamethasone is an inexpensive medication.

Please do not give this regimen to patients who are not on supplemental oxygen therapy. There appears to be a trend towards increased risk with these patients. We are not in the causing harm business. We are in the saving lives business. In patients who are not on supplemental O2, dexamethasone does not save lives.

Secondary outcomes:
Time until discharge from hospital. This was about 1 day faster in the dexamethasone group. Median 12 days vs. 13 days. Shaving a day off of the hospital bill is good.

Patients who started dexamethasone while not on the vent, on room air or supplemental O2, how many progressed to being on the vent or death. There was an 8% decrease of risk in this. The benefit was greater in patients who were on supplemental O2. There was a 23% decreased risk of ending up on the vent

The group is still trying to sort out if dexamethasone helps people get off of the vent faster.

If you’re asking for inflammatory marker numbers, they didn’t collect that. Nor any labs data. I forgive them for it. Same for physiologic numbers or virologic measures.

Many people thought that steroids would make things worse. But recruiting patients after their first week of illness shows us more of a predominant immunopathological response more so than viral replication.

Check this out in Podcast form!

Citation for the RECOVERY Trial:

Link to Press Release
UPDATED 7/20/2020
RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report [published online ahead of print, 2020 Jul 17]. N Engl J Med. 2020;10.1056/NEJMoa2021436. doi:10.1056/NEJMoa2021436
Link to Abstract on NEJM.com
Link to FULL PDF on NEJM.com

To read about many other things COVID that I have covered over the last several months, click here.

3 NEW TRIALS and a META-ANALYSIS: UPDATED ON 9/2/2020

Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. Published online September 02, 2020. doi:10.1001/jama.2020.17021
Link to Article

Dequin P, Heming N, Meziani F, et al. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. Published online September 02, 2020. doi:10.1001/jama.2020.16761
Link to Article

The Writing Committee for the REMAP-CAP Investigators. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. Published online September 02, 2020. doi:10.1001/jama.2020.17022
Link to Article

Meta-Analysis
The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. Published online September 02, 2020. doi:10.1001/jama.2020.17023
Link to Article

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