There has been a lot of confusion going on regarding the use of steroids in COVID. While steroids are important weapons in our armamentarium, it is critical to know when to administer steroids, the appropriate medication to use and the appropriate dosage for the appropriate period of time.

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A systemic inflammatory reaction in patients with severe COVID-19 will result in lung damage and multisystem organ dysfunction. Corticosteroids' strong anti-inflammatory properties have been suggested as a possible way to avoid or mitigate these negative effects. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) study, a multicentre, randomised, open-label trial in hospitalised COVID-19 patients, found that patients who were randomised to obtain dexamethasone had reduced COVID-19 death than those who received standard treatment..

In clinical trials, the safety and effectiveness of combining corticosteroids with an antiviral agent that targets the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the treatment of COVID-19 have not been thoroughly investigated. Nevertheless, there are potential explanations that a combined treatment like this may be useful to patients with advanced illness.

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Justification for corticosteroids in COVID-19 patients

The use of corticosteroids (mostly prednisone or methylprednisolone) in patients with other pulmonary infections has been linked to both positive and negative clinical outcomes. Prednisone treatment decreased the probability of mortality in patients with Pneumocystis jirovecii pneumonia and hypoxia; moreover, corticosteroid therapy was linked to virus clearance delays in outbreaks of other novel coronavirus infections (i.e., Middle East respiratory syndrome [MERS] and extreme acute respiratory syndrome [SARS]). Corticosteroid treatment tends to worsen the health effects of acute pneumonia caused by influenza viruses, including secondary bacterial infection and death.

In chronically ill patients with acute respiratory distress syndrome (ARDS), corticosteroids have yielded mixed outcomes. The use of corticosteroids in patients with ARDS was studied in seven randomised controlled trials with a total of 851 patients. Corticosteroid treatment decreased the risk of all-cause death (risk ratio 0.75; 95 per cent confidence interval, 0.59–0.95) and the length of mechanical ventilation as compared to placebo, according to a meta-analysis of these trial findings (mean difference, -4.93 days; 95 per cent CI, -7.81 to -2.06 days).

The RECOVERY study, a massive, multicentre, randomised, open-label trial conducted in the United Kingdom, is primarily responsible for recommendations on the use of corticosteroids for COVID-19. This study compared hospitalised patients who received dexamethasone for up to 10 days to those who received routine treatment. Patients who were randomised to receive dexamethasone had a lower 28-day mortality rate than people who received routine treatment. Patients that were mechanically ventilated or needed supplementary oxygen at the time of registration saw a boost. Patients who did not need supplemental oxygen at the time of admission did not benefit from dexamethasone.

Several smaller randomised clinical trials looked at corticosteroids in a variety of preparations, levels, and durations in patients with COVID-19. Following the publication of the RECOVERY trial findings, some of these studies were halted early due to poor participation.

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Which other corticosteroids apart from dexamethasone can be used?

In the absence of dexamethasone, other glucocorticoids such as prednisone, methylprednisolone, or hydrocortisone can be used.

The approximate daily dosage equivalents for these drugs to dexamethasone 6 mg (oral or intravenous [IV]) are as follows:

1. 40 mg prednisone or 32 mg methylprednisolone or 160 mg hydrocortisone
2. Corticosteroids differ in their half-life, duration of effect, and frequency of administration
   1. Dexamethasone, a long-acting corticosteroid with a half-life of 36 to 72 hours- Once-daily administration
   2. Corticosteroids with an intermediate half-life: prednisone and methylprednisolone- Once daily or in two separated doses daily
   3. Corticosteroid with a short half-life: hydrocortisone- Administer in two to four divided doses daily

Hydrocortisone is often used to treat septic shock in COVID-19 patients. In comparison to other corticosteroids observed previously in patients with ARDS, dexamethasone appears to lack mineralocorticoid action and hence has a negligible effect on sodium balance and fluid volume.

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Monitoring, adverse outcomes, and drug reactions

Clinicians should carefully track dexamethasone-treated patients with COVID-19 for detrimental effects (e.g., hyperglycaemia, secondary infections, psychiatric effects, avascular necrosis). Extended systemic corticosteroid use can raise the risk of dormant infection reactivation (e.g., hepatitis B virus [HBV], herpesvirus infections, strongyloidiasis, tuberculosis).

The possibility of dormant infections reactivating after a 10-day period of dexamethasone (6 mg once daily) is unknown. When starting dexamethasone, adequate screening and care should be considered to minimise the risk of Strongyloides hyperinfection in patients at high risk of strongyloidiasis (e.g., patients from tropical, subtropical, or humid, temperate areas, or those engaged in agricultural activities) or fulminant reactivations of HBV.

Dexamethasone induces cytochrome P450 (CYP) 3A4 to a modest extent. As such, it can decrease the concentration and possible effectiveness of concomitant CYP3A4 substrate drugs. Clinicians should do a prescription regimen analysis on each patient to identify possible drug interactions. While no systematic study of remdesivir and dexamethasone coadministration has been conducted, no clinically relevant pharmacokinetic association is expected.

Dexamethasone can be continued for a maximum of ten days or until before the patient is discharged from the hospital, whichever occurs first.

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Pregnancy-related considerations

Betamethasone and dexamethasone, both of which are believed to cross the placenta, are commonly used to prevent neonatal symptoms of prematurity in mothers who are at risk of preterm birth. The NIH panel suggests using dexamethasone in hospitalised pregnant women with COVID-19 who are mechanically ventilated or who need supplemental oxygen but are not mechanically ventilated due to the possible advantage of reduced maternal mortality and the low risk of foetal adverse effects for a short course of dexamethasone treatment.

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Considerations in paediatric patients

The safety and efficacy of dexamethasone or other corticosteroids for COVID-19 therapy in paediatric patients have not been thoroughly studied. Importantly, the RECOVERY study did not have a large number of paediatric patients, despite the fact that COVID-19 mortality is slightly lower in children than in adults. As a result, when extrapolating the RECOVERY trial findings to patients above the age of 18, extreme caution is advised. In paediatric patients with COVID-19 respiratory disease who need mechanical ventilation, dexamethasone can be helpful. The use of dexamethasone in patients who need other sources of supplementary oxygen treatment should be treated on an individual basis, and it is usually not prescribed for paediatric patients who only need minimal amounts of oxygen support (i.e., nasal cannula only). More research is required to examine the use of steroids in the treatment of COVID-19 in paediatric patients, including multisystem inflammatory syndrome.

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Clinical research

Several clinical trials evaluating corticosteroids for COVID-19 therapy are either ongoing or in the planning stages.

Steroids precautions

Steroids should be specifically discouraged in:

• Asymptomatic patients
• Patients with minimal clinical signs lasting for a week
• Patients with CT score below 8 and illness period around 5 to 7 days
• In the viral replication stage (high fever with normal CRP and CT)

Steroids should be preferred in all moderate and severe cases. Patients with a SPO2 of less than 94, regardless of the day on which symptoms began. Any of these patients can receive daily doses of 40–120 mg methylprednisolone or 6 mg dexamethasone.

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Steroid's role in mild COVID-19 disease

Mild cases in the second week of fever, malaise, myalgia, headache, and nausea (all of which are indicative of hyper inflammation) can be treated with a low dose of methylprednisolone (4–16 mg per day or equivalent of another steroid for 5 to 7 days).

This view argues solely on the basis of expert opinion. To counteract immune dysregulation, the anti-inflammatory steroid should be started early in the pulmonary process. The optimal time to initiate steroids is after the eighth day of symptoms when the virus has a low propensity for replication and the inflammatory reaction is persistent.

It is critical to administer steroids at the appropriate time, with the appropriate medication, at the appropriate dosage, and for the appropriate period. Methylprednisolone is superior to dexamethasone, and prednisolone is superior to dexamethasone. Methylprednisolone penetrates the lungs and binds to the glucocorticoid receptors more effectively than any other steroid, resulting in the strongest anti-inflammatory effect.

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