Dexamethasone for COVID-19 infection is not a surprise. It has been on the WHO's list of essential medicine since 1977 [Ref]. Dexamethasone is already being used in patients with various inflammatory and neoplastic diseases.

A list of the indications of dexamethasone is given here (Dexamethasone - Drug Details). Glucocorticoids have potent anti-inflammatory effects. The anti-inflammatory effects of various glucocorticoids differ.

Dexamethasone is thought to be between 25 and 30 times more potent than hydrocortisone and six times more potent than prednisone. Although methylprednisolone has not been studied in clinical trials, it has been used as off-label medicine in most hypoxemic patients infected with COVID-19.

The implementation of glucocorticoids in COVID 19 infection - Our experience:

In our hospital, we use methylprednisolone 1 - 2 mg/kg in two divided doses in all patients who are hypoxemic. At the peak of the pandemic, when all our hospital beds were full and there was no bed available in any of the hospitals in the ICUs, we also attempted large dosages of pulse methylprednisolone, given once daily for three days at a dose of 1 gm.

One of our patients who had an oxygen saturation of 78% despite double oxygen support (high flow oxygen via non-rebreathing mask with oxygen bag plus oxygen via nasal cannula) improved after 48 hours. His saturation improved to 91% after 48 hours with support and was later discharged.

Is It Rational To Use Dexamethasone or Other Corticosteroid in COVID-19 infection?

Patients with COVID 19 infection undergo three stages of the disease:

• The viremic stage
• The pulmonary stage
• The inflammatory stage

The Viremic Stage:

Patients in the viremic stage behave like most other viral infections. These patients have body aches, myalgias, aches and pains, fever, sore throat, dry cough, and anosmia.

At this stage, patients may best benefit from antiviral medications such as remdesivir. It is also important to know that at this stage, the use of glucocorticoids may be counterproductive.

Glucocorticoids (prednisone or dexamethasone) may delay viral clearance and theoretically enhance the replication of the COVID 19 virus.

Thus, dexamethasone or any glucocorticoid should be avoided in the early viremic stage.

Unfortunately, most patients receive unnecessarily glucocorticoids.

The Pulmonary Stage:

The pulmonic stage is the stage of pulmonary manifestation. Patients at this stage may develop a high-grade fever, tachypnea, exertional dyspnea progressing to dyspnea at rest, and chest pain.

Patients in the pulmonic stage may benefit from anti-inflammatory drugs, anticoagulants, antivirals, or convalescent plasma.

The Inflammatory Stage:

The third stage corresponds to a hyperinflammatory state that may manifest as worsening chest infiltrates, hypoxemia requiring oxygen support, hypotension, and organ dysfunction.

Patients in the inflammatory stage may benefit from corticosteroids, Interleukin-6 inhibitors, JAK-2 inhibitors, and anticoagulants.

Dexamethasone for COVID 19 infection: The "RECOVERY TRIAL"

Randomized Evaluation of COVID-19 Therapy was conducted to answer the following clinical question:

Would dexamethasone in addition to standard care lessen 28-day mortality in hospitalized COVID-19 patients than standard care alone?

It was a randomized open-label multicentric controlled clinical trial. Patients in the study either received usual care alone or received usual care along with dexamethasone orally or intravenously at a dosage of 6 milligrams once per day for 10 days. Mortality at 28 days following randomization was the main outcome that was evaluated.

 Secondary outcomes included:

• Mortality by specific causes
• Receiving hemodialysis or hemofiltration for the kidneys
• Patients who were not undergoing invasive mechanical breathing at randomization and the time to hospital discharge
• Significant cardiac rhythm
• Receiving invasive mechanical ventilation (including ECMO) later or passing away

Who were the study candidates?

Only patients who fulfilled the following requirements were included in the study:

• Either clinically suspected or tested positive the SARS-CoV-2 virus
• Aged 18 or younger at first (age limit removed on May 9th, 2020)
• There are no medical issues that, in the attending clinician's opinion, would place the patient at considerable risk if they participated in the trial.
• Women who were expecting or nursing were eligible.

At study randomization:

• At Randomization:
  • IMV/ECMO: 16.0%
  • O2 Therapy: 60%
  • No O2: 24.0%
• A total of 6425 patients were randomized to receive either:
  • Dexamethasone (Total patients in this group: 2104 patients)
  • Usual Care (Total patients in this group: 4321 patients)

Outcomes of the study:

• The overall mortality in the study groups:
  • Patients in the group receiving standard care: 24.6%
  • 21.6 percent of patients were in the dexamethasone with usual care group 

RR: 0.65, CI: 95% (0.51 - 0.82), P-value: < 0.001

• The 28 days-mortality in patients on IMV:
  • Patients in the usual care group: 40.7%
  • Patients in the dexamethasone plus usual care group: 29%

P-value = 0.001, RR = 0.65, CI = 95 percent (0.51 - 0.82).

• Patients undergoing oxygen therapy without IMV have a 28-day death rate of:
  • Patients in the group receiving standard care: 25%
  • 21.5 percent of patients were in the dexamethasone plus usual care group.

P-value = 0.002, RR = 0.80, CI = 95 percent (0.70 - 0.92).

• The 28-day death rate in individuals not getting oxygen support or invasive mechanical ventilation (IMV):
  • 13.2% of patients in the usual care group
  • 17% of patients were in the dexamethasone plus usual care group.

RR is 1.22, CI is 95% (0.93-1.61), and P-value is 0.14.

What is the study telling us? Which patients should receive dexamethasone for COVID-19 infection?

The take-home message in the study is that patients who require respiratory support and especially very sick patients such as those requiring invasive mechanical ventilation may benefit most from dexamethasone treatment in addition to the usual care.

Dexamethasone is a cheap and long-acting potent corticosteroid. It may be used only in hospitalized patients who require respiratory support.

Patients in the viremic stage should best avoid the use of dexamethasone or any other corticosteroid drug as it may be counterproductive. This point has not been concluded by the author of the study but is indirectly evident.

You can see that patients in the early symptomatic stage did not benefit from dexamethasone use. This correlates with the viremic stage where the use of corticosteroids may be counterproductive.

In Conclusion:

When administered intravenously or orally once daily at a dose of 6 mg of dexamethasone, hypoxemic hospital patients have a lower 28-day death rate.