For historical context, today is 11/19/2021 when I have provided a major update to this page with the citations. Like everything else on my page, it is a work-in-progress. The guidelines are still recommending 6mg of dexamethasone per day for oxygen-requiring patients with COVID-19. I have extensively covered the data behind doing so on this post. Since this summer (2021), however, several papers were published supporting the utilization of methylprednisolone in COVID. Said papers will be cited and covered shortly but my underlying intuition is that these patients who end up needing me in the ICU have an inflammatory process that has far exceeded that which can be controlled with dexamethasone. Not to mention, when this whole pandemic began, the glucocorticoid that I was administering to patients before the data of the RECOVERY trial was methylprednisolone. Prior data showed that it has shown the greatest benefit in ARDS. I have been covering these therapies since April of 2020.

Pulse-Dose Methylprednisolone in COVID

This part was written in January of 2021. Since early April of 2020, I have been using corticosteroids to treat my COVID-19 patients in the ICU. I even posted about in mid-April when Meduri wrote an opinion piece on the matter prior to the RECOVERY trial being published in July of 2020. Let’s be clear that administering glucocorticoids to everyone who has COVID is not a smart idea. Giving it too early in the viral phase may actually cause harm. The time to check the box and start providing corticosteroids when the patients start their hyperinflammatory phase. We’re thinking this is around day 7 or 8, right? This is a small study of 68 patients that was conducted in Iran. Hat tip to all the authors for their strong work. Here, they are looking at using pulse-dose methylprednisolone in COVID patients.

How does this compare to the RECOVERY Trial?

For those asking how this compares to dexamethasone I have to answer that we do not know. It’s apples and oranges to compare the two. The study was conducted between April and June of 2020 and the RECOVERY trial, as mentioned, was published on July 17th. RECOVERY showed a mortality improvement when using glucocorticoids. It should not be a surprise that we are seeing a mortality improvement here as well.

Dose of Methylprednisolone provided in COVID

The dose of Methylprednisolone used in this trial was 250mg IV daily for 3 days.

How much does each dose of Methylprednisolone cost?

Average wholesale price per UpToDate of Methylprednisolone in the US for 125mg is between $9.36 and $13.98. Multiply that by two and you’re looking at a max of $28 per day.

What types of patients were enrolled?

In this single-center, they conducted a single-blind, two-arm parallel, RCT looking at sick COVID patients. Their sats were <90%, their CRP was >10 and they also had the resources to check IL-6’s on everyone which I can’t do. If people were too sick, like sats <75% or had a positive procalcitonin, they were not invited to play. In addition, all patients also got hydroxychloroquine, lopinavir, and naproxen.

When comparing the two groups, there were more diabetics in the control group but it seems as if the study arm patients were sicker on enrollment because they were certainly breathing faster and 47% of the patients were breathing more than 24 breaths per minute. The d-dimer was higher in the study arm but not statistically significant (p=0.057).

What did they find?

Surprise surprise! The methylprednisolone pulse doses helped patients. They improved mortality and also improved the pulmonary involvement, oxygen requirement, and inflammatory markers. Let’s not forget that patients also got better faster with a median duration of 11.8 days versus 16.4 in the control arm.

So what do we do with this information?

This trial was definitely not as robust as the RECOVERY trial. And it definitely is thought provoking as to why it was received in July of 2020 by the journal, then accepted after revision in September, but only published online on 12/24. I think it’s worthwhile to give some sicker people once they arrive in the ED a few slugs of methylprednisolone to assess if they get better faster and go from there. We see too many people just linger forever after getting the dexamethasone. Perhaps we need a bigger slug of steroids. After all, remember that the 6mg dose was made up out of thin air. It’s not like they randomized patients to get 6mg vs. 12mg and the 6mg group had the best outcomes. What do you all think? Will you be using Methylprednisolone in COVID?

Citations for Methylprednisolone in COVID:

Villar J, Confalonieri M, Pastores SM, Meduri GU. Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019. Crit Care Explor. 2020 Apr 29;2(4):e0111. doi: 10.1097/CCE.0000000000000111. PMID: 32426753; PMCID: PMC7188431.
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Edalatifard M, Akhtari M, Salehi M, Naderi Z, Jamshidi A, Mostafaei S, Najafizadeh SR, Farhadi E, Jalili N, Esfahani M, Rahimi B, Kazemzadeh H, Mahmoodi Aliabadi M, Ghazanfari T, Sattarian M, Ebrahimi Louyeh H, Raeeskarami SR, Jamalimoghadamsiahkali S, Khajavirad N, Mahmoudi M, Rostamian A. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J. 2020 Dec 24;56(6):2002808. doi: 10.1183/13993003.02808-2020. PMID: 32943404; PMCID: PMC7758541.
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Edalatifard M, Akhtari M, Salehi M, Farhadi E, Jamshidi A, Mahmoudi M, Rostamian A. Reply: Is high-dose glucocorticoid beneficial in COVID-19? Eur Respir J. 2021 Apr 15;57(4):2100324. doi: 10.1183/13993003.00324-2021. PMID: 33602862; PMCID: PMC7898159.
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Ko JJ, Wu C, Mehta N, Wald-Dickler N, Yang W, Qiao R. A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients With COVID-19. J Intensive Care Med. 2021 Feb 25:885066621994057. doi: 10.1177/0885066621994057. Epub ahead of print. PMID: 33632000.
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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.
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Salton F, Confalonieri P, Meduri GU, Santus P, Harari S, Scala R, Lanini S, Vertui V, Oggionni T, Caminati A, Patruno V, Tamburrini M, Scartabellati A, Parati M, Villani M, Radovanovic D, Tomassetti S, Ravaglia C, Poletti V, Vianello A, Gaccione AT, Guidelli L, Raccanelli R, Lucernoni P, Lacedonia D, Foschino Barbaro MP, Centanni S, Mondoni M, Davì M, Fantin A, Cao X, Torelli L, Zucchetto A, Montico M, Casarin A, Romagnoli M, Gasparini S, Bonifazi M, D’Agaro P, Marcello A, Licastro D, Ruaro B, Volpe MC, Umberger R, Confalonieri M. Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia. Open Forum Infect Dis. 2020 Sep 12;7(10):ofaa421. doi: 10.1093/ofid/ofaa421. PMID: 33072814; PMCID: PMC7543560.
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Papamanoli A, Yoo J, Grewal P, Predun W, Hotelling J, Jacob R, Mojahedi A, Skopicki HA, Mansour M, Marcos LA, Kalogeropoulos AP. High-dose methylprednisolone in nonintubated patients with severe COVID-19 pneumonia. Eur J Clin Invest. 2021 Feb;51(2):e13458. doi: 10.1111/eci.13458. Epub 2020 Dec 1. PMID: 33219551; PMCID: PMC7744876.
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Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, Safe IP, Borba MGS, Netto RLA, Maciel ABS, Neto JRS, Oliveira LB, Figueiredo EFG, Oliveira Dinelly KM, de Almeida Rodrigues MG, Brito M, Mourão MPG, Pivoto João GA, Hajjar LA, Bassat Q, Romero GAS, Naveca FG, Vasconcelos HL, de Araújo Tavares M, Brito-Sousa JD, Costa FTM, Nogueira ML, Baía-da-Silva DC, Xavier MS, Monteiro WM, Lacerda MVG; Metcovid Team. Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial. Clin Infect Dis. 2021 May 4;72(9):e373-e381. doi: 10.1093/cid/ciaa1177. PMID: 32785710; PMCID: PMC7454320.
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