My understanding is that Dexamethasone reduces inflammation triggered mediator response and interaction and thus production of Nitric Oxide, which at high levels inhibits energy supply via ATP production during aerobic glycolysys (Krebs Cycle) and the results in cell death and consequently sequential multisytem failure and organ death from asphyxiation. Cells cannot utilize oxygen to produce energy for survival. Best Dietmar

It is used only in severe cases and can save 1 in 8 (June 17, CNN). It's not an antiviral drug at all and we need to find that urgently and for all sure.

The hype of dexa as a cure by the media can have devastating impact on the general population.

Even contacts and mild cases will start start abusing its use which can lead to side effects and opportunistic infections, specially tuberculosis in a country like mine..

The trial has found encouraging results in a subset of population which further needs larger studies and the media is irresponsibly declaring it as a wonder drug

Dexamethasone for COVID-19 in DISCOVERY Trial - Hope or hype?

Even when the full results of dexamethasone use in patients with COVID-19 are still not published, and the inclusion, exclusion criteria for the DISCOVERY study are not available, the breaking news on print and electronic media are highlighting the benefits of dexamethasone.

I have seen even doses as much as 20 mg daily being given, while a dose of 6 mg daily by intravenous or oral was used in the trial for 10 days in Discovery trial. People has started using it even in patients with heart failure, uncontrolled diabetes and hypertension.

Very important point to consider will be how many of these survivors of COVID-19 from ICU were able to have an independent survival. Given the fact that most of the patients needing ICU admissions are old, physical deconditioning, osteoporosis, muscle weakness would add up to the challenge of rehabilitating such patients.

Yes, I agree. A "cure" definitely not. Already used in most of the serious cases and those with wheezing anyway. You are correct that the public will see this in the news and start using it in all exposures as a "cure" causing very serious problems needlessly. This is malpractice on the part of the media if that happens.

Thank you for your continued support. Stay safe.

Public: Do not take steroids unless your treating medical doctor gives them too you!

It is not a cure.. I am just very afraid of the perceived dangers that will accompany the recent media hype and consequent use as many nations lack research capabilities and just rely on other nations to channel a course of action.. and sadly Covid19 is a virus.. mutating and manifesting differently in different places..

Let's look at this write up talking about the dangers accompanying dexa use

https://www.researchgate.net/deref/http%3A%2F%2Fdx.doi.org%2F10.6084%2Fm9.figshare.12509807?_sg%5B0%5D=8XxZ6Vlf0EUO08K6I8e1PUpSGv3E1mUz1DxucJko1Rvve1koTC-G08STLN3O7wmpb_p_SQH_1m5rEozRKITE3BMIuw.2OrUaJVkssxCh0MK8cJf-97EMwFHGM2L7IAt0PS4b9-G9i3TWADe2voc-jluVpoCQPxgAxoSYn_6CKqFC8ob0g

it may work by preventing overwhelming immune response which kills the patient by the inability to utilize oxygen within the cell to produce energy for cell function

@dietmar.. are you saying Prednisolone would not be more appropriate in arresting a cytokine storm? I have a problem understanding why a glucocorticoid is more suited while one which has some minerocorticoid wont do..

no, both work the same way

@dietmar.. why the hype about dexa? And not prednisolone.. Considering that in management of chemotherapy taking cancer patients we alternate use to eliminate chemo side effects..

Covid-19 is usually a mild self-limiting illness that does not require any treatment.

Current evidence based medicine is based on the presumption of significance when P

https://www.researchgate.net/publication/342282696_THE_PERCEIVED_ACCOMPANYING_DANGERS_OF_DEXAMETHASONE_A_CORTICOSTEROID_USE_IN_COVID-19_MANAGEMENT

Steroids in COVID-19. Today an article in the NYTimes, which included this paragraph: "’I've heard about a treatment called dexamethasone. Does it work?

The steroid, dexamethasone, is the first treatment shown to reduce mortality in severely ill patients, according to scientists in Britain. The drug appears to reduce inflammation caused by the immune system, protecting the tissues. In the study, dexamethasone reduced deaths of patients on ventilators by one-third, and deaths of patients on oxygen by one-fifth."

Again, this surprises me, as I would have thought that most of the seriously ill patients would get it as standard of care. This is not likely a double blind placebo controlled study, so not proof that steroids work, as has already, to my knowledge, been proven. Who would have ethically been denied this treatment? makes me wonder. Thank you for your support. Gary Ordog, MD June 20, 2020.

careful selection of patients on an individual basis is a must before starting. Benefits may be evident, but there should a constant vigil on the risks and complications. The risk-benefit ratio can only be judged by the treating physician

Consideration: Todays discussion in "Doctors' Guide Alert":

COVID-19 Status message Your comment has been posted. June 22, 2020 High serum cortisol tied to greater risk of death from COVID-19 Serum cortisol concentration may potentially serve as another marker to help doctors identify which patients with coronavirus disease 2019 (COVID-19) are more likely to need intensive care, a new study finds. According to results published in The Lancet Diabetes & Endocrinology, cortisol levels in patients with COVID-19 were significantly greater than those without, ranging up to 3241 nmol/L, indicating a cortisol stress response that is "perhaps higher than is observed in patients undergoing major surgery," reported Tricia Tan, Imperial College London, London, UK, and colleagues. They also found high cortisol concentrations were linked to increased mortality and reduced median survival, "probably because this is a marker of the severity of illness." They noted that in their cohort study "cortisol seemed to be a better independent predictor than were other laboratory markers associated with COVID-19, such as C-reactive protein (CRP), D-dimer, and neutrophil-to-leukocyte ratio." The study looked at acute cortisol concentrations in patients with a clinical suspicion of COVID-19 admitted to three large hospitals in London, UK, from March 9 to April 22, 2020. Only baseline cortisol measurements made within 48 hours of admission for suspected COVID-19 or diagnosis of COVID-19 during a hospital admission were included. Patients had a standard set of blood samples drawn, including full blood count, creatinine, CRP, D-dimer, and serum total cortisol. Those with pre-existing hypoadrenalism, concurrent systemic glucocorticoid treatment, or who had cortisol measured as part of a diagnostic test (eg, a synacthen test) were excluded. A total of 535 patients with cortisol measurements were available for analysis, of whom 403 were diagnosed with COVID-19 on the basis of either a positive real-time RT-PCR test of a nasopharyngeal swab (356 [88%]) or a strong clinical and radiological suspicion of COVID-19, despite negative swab testing (47 [12%]). In the group of patients with COVID-19, the mean age was 66.3 years (SD 15.7) and 240 (59.6%) were men. The most frequent comorbidities in this group were hypertension (191 [47.4%]), diabetes (160 [39.7%]), cardiovascular disease (94 [23.3%]), chronic kidney disease (50 [12.4%]) and a current diagnosis of cancer (38 [9.4%]). A total of 112 (27.8%) of the patients with COVID-19 died during the study period, compared to 9 (6.8%) in the non-COVID-19 group (p

Dear Dr. Ordog,

Thank you for your comment. The immunopathology in the lung is a cytokine storm type. So it is now very surprising that after this long time of work it is announced that Dexa would work!!?? I have discussed the issue of corticosteroids on Article Are Losartan and Imatinib Effective Against SARS-CoV2 Pathog...

The behavior of corticosteroids cannot be predicted as they may increase Th17 in the inflammatory processes, exactly the thing that happens in COVID19. In addition, in this disease we do need an immunomodulator not an immunosuppressor. I would rather wait and see what other data is distributed about Dexa; might it follow the path of hydroxychloroquin?

Well put Dr Reza.

Dexamethasone - A broad spectrum Livesaving Streoid - Can be used for severe infection but not Covid specific .

Hi all participants and have a nice week. In the following RG open question I attempt to search causes of the Lombardia hyper cluster of COVID19,

https://www.researchgate.net/post/The_novel_Coronavirus_in_N_Italy_Lombardia_COVID19_2019nCoV_SARSCoV2_shows_a_fatality_rate_compatible_with_SARS-MERS_Why

a very worst case.

In order to obtain data, there are extensive bibliographical lists about

--oral-fecal contagion

--chemicals vs. SARS-CoV/2

--receptor ecosystem

--animal reservoirs

--Guillain-Barrè syndrome

-- co-infection (other local CoV)

-- comparative data vs. others world hyper clusters

I hope this is an interesting point to obtain data for this dramatic situation in N. Italy (and Central Europe), in order to prevent similar evolution in the next future.

-sv-

My point of surprise, and the reason for my question: I reiterate. My impression of the standard of care in any Emergency Department, and ICU/CCU, for a patient in ARDS, with wheezing, etc., includes high dose steroids. That is why I was surprised that they were able to find such patients who were not treated as such.

Our experience of dexamethasone in severe COVID-19 patients.

The recommended dose of dexamethasone is 6 mg iv or oral up to 10 days or until hospital discharge. It can reduce mortality in COVID-19 patients on ventilator by 35% and patients needing oxygen by 20% (1)

We have used dexamethasone in severe cases of COVID-19 pneumonia with respiratory failure on high flow nasal cannula oxygen therapy and had salutory effects.

1.Preprint Effect of Dexamethasone in Hospitalized Patients with COVID-...

My concern is that I still do not understand the mechanism of action.. asides explanations regarding arresting cytokine storm... what special thing does dexa do?

Dexamethasone is used to treat patients with COVID-19 who do not require supplemental oxygen due to its immunosuppresent and potent antiflammatory effect .

COVID-19 infection is still under investigation, and we still do not know real pathophysiology mechanism of virus. The giving of dexamethasone (or any other steroids) just only suppresses immunology response in patients, but definitely is not healing. The question is how smart it is to suppress immunology system. In case of cytokine storm, dexamethasone wouldn’t help. This principle is reminding me on the attitude of old colleagues who said sometimes: If you do not know what is happening with patient, give him dexamethasone! (or some other steroid).

It is not a cure but it reduces the symptoms of covid-19 for critically ill patients

the challenge is to find the correct subset and the correct timing of using dexa.

Unfort it has been included in national guidelines for all mod to severe patients.

@Nikola Bradic

Exactly my thoughts.. In cytokine storm, Dexa won't work apart from certain anti inflammatory action it possess.. however I have been looking at this Acetyl salicylate (Aspirin) working on a paper on that.. responses from patients who have taken this either while still asymptomatic for symptoms of Heart attack or for some other reason else, seem to be rewarding..

Should this be the case, then we have to reclassify Covid-19 as now a Cardiovascular/Blood Physiology disease.. rather than a Respiratory disease.... this then will further explain basis of certain attributes, immunology responses etc.. this is my thought..

The World Health Organization (WHO) has recently updated guidance on steroids in COVID-19 recommending the use of systemic corticosteroids in severe and critical COVID-19 disease.

It is intended to apply worldwide, and is available at

https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1

It reduces inflammation resulted by exaggerated immune response in response to Covid 19 infections.

Gary Joseph Ordog (personal opinion only)

• County of Los Angeles Public Health

COVID-19: The Ultimate Treatment? Discussion

• Started 1 day ago
• Apparently one of the first drugs given to the POTUS was in fact, dexamethasone

The POTUS and FLOTUS were reported to be positive for mRNA SARS-CoV-2 yesterday. Others on the White House staff have also contracted the virus recently. My theory is that the Most Powerful Man on Earth is probably on the best treatment that money and power can acquire. So what is that "best" treatment in existence? The news today hinted at what he is on, this may not be true, and he may be on other things that were not reported. Also, big news, there is no mention of HCQ!!Trump taking Regeneron, Remdesivir therapy for coronavirus diagnosis: ex-WH doctor explainsThe president was taken to Walter Reed Medical Center 'out of an abundance of caution' Friday nightThe House physician on Trump’s medical care at Walter ReedPresident Trump is taking experimental coronavirus drugs Remdesivir and Regeneron after being diagnosed with COVID-19 this week, his former White House physician told "Fox & Friends Weekend.""The two of those in combination should help clear the virus out of his body much sooner than his body could do it on its own," Dr. Ronny Jackson said Saturday morning.TRUMP TWEETS FROM HOSPITAL AS DOC CONFIRMS REMDESIVIR TREATMENT: ‘GOING WELL, I THINK!’The president was taken to Walter Reed National Military Medical Center "out of an abundance of caution" Friday night and is being treated with experimental drugs in response to a compassionate use request."The Regeneron product is an antibody product," Trump's former doctor explained."They found two particular antibodies in the research they did coming up to developing this product. One of them attaches to the spiked protein and prevents the virus from entering into the host cell, the human cell. So what it does basically is it attaches itself to the virus and it disables the virus where it can't get into the body, into the cells of the body and cause infection, and so that essentially drops the viral count," he said. "Eventually your body clears those viruses."REGENERON IS TRUMP'S COVID-19 TREATMENT: WHAT TO KNOWThe other drug, Remdesivir, he explained, stops viral replication: "So we're blocking the virus that's already in his body and we're preventing the replication of the virus with the Remdesivir," he said.Jackson, who helped design and build the presidential wing at Walter Reed, predicts that Trump will spend three to four days there."I think they'll monitor him and check to make sure the fever is not getting worse and that his symptoms are improving. After a couple of days, I think he will be back to the White House," he said.Prior to moving to Walter Reed, on Friday afternoon, Dr. Sean P. Conley, the president’s physician, released an update on the president's condition.“Following PCR-confirmation of the president’s diagnosis, as a precautionary measure he received a single 8-gram dose of Regeneron’s polyclonal antibody cocktail,” a memo released Friday afternoon by Dr. Sean P. Conley, the president’s physician stated. "He completed the infusion without incident.”"In addition to the polyclonal antibodies, the president has been taking zinc, Vitamin D, famotidine, melatonin and a daily aspirin," Conley said. Apparently, they are not ill enough to stop working, and may be following isolation while performing their duties. Mike Pence is negative in testing.We all await the results of this trial. I wish all of those involved a 'speedy recovery.' Thank you, Gary Ordog, MD, October 03, 2020. Stay safe and stay healthy!

October 02, 2020: Two days ago the POTUS and FLOTUS contracted the

COVID-19. The POTUS, it was announced today had been put on dexamethasone. The information that the public is getting is questionable, at best. As well as the effects of hypoxemia (his O2 saturation allegedly down to 93%, probably cognitive changes not prominent until 85%, plus obviously he was on supplemental oxygen.) but, it is a good thing that the incidence of steroid psychosis is low, with a short course in an otherwise 'healthy' person. This unfortunate POTUS has been called psychotic by a large group of psychiatrists previously (obviously politically motivated and unsuccessful), so he really does not need this added stress. Fortunately, the news (again, if you can believe the news) is that POTUS has improved and may be going home tomorrow. We wish them well. Stay safe and thank you for your support.

October 06, 2020 Published today in JAMA to support the use of steroids for COVID-19.

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19A Meta-analysis

Educational Objective To understand the association between administration of systemic Corticosteroids And mortality among critically ill patients with COVID-19 JAMAOctober 6, 2020Original InvestigationArticle Information and Disclosures The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group Read article on JAMA NetworkCOVID-19 Resource Center.

Question Is administration of systemic corticosteroids associated with reduced 28-day mortality in critically ill patients with coronavirus disease 2019 (COVID-19)?

Findings In this prospective meta-analysis of 7 randomized trials that included 1703 patients of whom 647 died, 28-day all-cause mortality was lower among patients who received corticosteroids compared with those who received usual care or placebo (summary odds ratio, 0.66).

Meaning Administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality in critically ill patients with COVID-19.

Abstract

Importance Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.

Objective To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality.

Design, Setting, and Participants Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios.

Exposures Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).

Main Outcomes and Measures The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events.

Results A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as “low” for 6 of the 7 mortality results and as “some concerns” in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P 

Why does the administration of systemic corticosteroids, reduce mortality? Hypothesis: because it suppresses the eneration of NO which impairs energy production within the Krebs Cycle. Did sombody mesure arginine levels in the Urine as a proof of changing NO generation? DHWittmann, MD, PhD.

Good point. I know of no urinary arginine studies. But we did some of the initial NO studies using oral arginine and citrulline.

FEBRUARY 4, 2021

IVIG plus methylprednisolone linked to more favourable fever course in children with multisystem inflammatory syndrome

Treatment with intravenous immunoglobulin (IVIG) and methylprednisolone, compared with IVIG alone, was associated with a more favourable fever course in multisystem inflammatory syndrome in children (MIS-C), according to a study published in the Journal of the American Medical Association. In addition, the combination therapy was also associated with less severe acute complications, including acute left ventricular dysfunction and hemodynamic support requirement. 

A total of 106 children, with a median age of 8.6 years, who fulfilled the World Health Organization definition of MIS-C were included in this retrospective cohort study which started on April 1, 2020, with follow-up ended on January 6, 2021. More than half (52%) of the children were female. The primary outcome was treatment failure, defined as persistence of fever for 2 days after the introduction of initial therapy or recrudescence of fever within 7 days after the initial therapy. Meanwhile, secondary outcomes included second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit (PICU).

Of the children, 34 received IVIG and methylprednisolone while 72 received IVIG alone. The dosage of IVIG was 2 g/kg for all patients. Among children in the IVIG and methylprednisolone group, 30 received methylprednisolone at 0.8 to 1 mg/kg every 12 hours (maximum of 30 mg for 12 hours) for 5 days, while the 4 remaining children received a bolus of 15 to 30 mg/kg/d of methylprednisolone for 3 days.

Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group while 37 of 72 (51%) in the IVIG alone group did not respond to treatment. When 32 children in the IVIG and methylprednisolone group were propensity-score matched with 64 children in the IVIG alone group, the researchers found that treatment with IVIG and methylprednisolone was associated with a lower risk of treatment failure (absolute risk difference, −0.28 [95% confidence interval (CI), −0.48 to −0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = 0.008). 

Similarly, IVIG and methylprednisolone therapy, compared with IVIG alone, was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, −0.22 [95% CI, −0.40 to −0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = 0.004), hemodynamic support (absolute risk difference, −0.17 [95% CI, −0.34 to −0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]; P = 0.01), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, −0.18 [95% CI, −0.35 to −0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]; P = 0.007). The duration of PICU stay was also significantly shorter among those treated with IVIG and methylprednisolone compared with those on IVIG alone (median, 4 vs 6 days; difference in days, −2.4 [95% CI, −4.0 to −0.7]; P = 0.005). 

“MIS-C is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown,” wrote Naïm Ouldali, MD, Université de Paris, Paris, France, and colleagues. 

“Corticosteroid use is currently one of the few validated therapeutics in severe respiratory adult forms of COVID-19. The findings in the current study suggest that corticosteroids may also be beneficial in MIS-C, possibly acting systematically as a potent inhibitor of SARS-CoV-2–induced inflammation,” the authors noted. “Combined with findings of studies reporting MIS-C cases in young adults, there may be common pathways between severe respiratory adult forms of COVID-19 and MIS-C.”

“Additional studies are warranted to understand the mechanisms underlying a possible corticosteroid effect in MIS-C and in severe forms of COVID-19,” the authors added. 

Reference: https://jamanetwork.com/journals/jama/fullarticle/2776054SOURCE: Journal of the American Medical Association

I think DEX is also harmful in Covid-19.

Erythropoietin (EPO) would be a more " potent inhibitor of SARS-CoV-2–induced inflammation" and more of a "cure".

https://www.researchgate.net/post/Covid-19_Erythropoietin_EPO_deficiency_syndrome2

No difference between 12 mg vs 6 mg Dexamethasone in COVID-19 patients with hypoxic respiratory failure

Please have a look at this article:

https://jamanetwork.com/journals/jama/fullarticle/2785529