Interactions Between Steroidal Medications and COVID-19

Introduction

Steroids or corticosteroids are medications that resemble hormones called cortisol. These medications reduce inflammation and treat many conditions, such as:

• Asthma.

• Inflammatory diseases.

• Multiple sclerosis.

Regular intake of steroids can affect the immune system and increases the risk of developing COVID-19 or other severe illnesses. Corticosteroids are different from anabolic steroids, which replicate the testosterone hormone. Anabolic steroids have medical uses, although they are largely used for recreation to build up muscle and improve sports performance.

How Are Corticosteroids and COVID-19 Related?

Corticosteroids are manufactured drugs that replicate the hormone cortisol. The adrenal glands, which are located in the kidney, produce cortisol. Corticosteroid is the most commonly prescribed drug. They are used to treat,

• Asthma (lung inflammation).

• Allergies.

• Psoriasis (skin infection).

• Chronic obstructive pulmonary disease (COPD).

• Lupus (auto-immune disease).

• Rheumatoid arthritis (bone inflammation).

Corticosteroids help to reduce inflammation by binding to the receptors that suppress the activity of the immune system. Long-term use of steroids can result in compromised immunity, and the person can get affected by COVID-19 very easily. Long-term use of steroids is associated with the following:

• Increased upper respiratory tract infection.

• Increased viral replication.

• Delayed viral clearance.

• Increased risk of secondary infection.

Some steroids cause the removal of antiviral drugs like Remdesivir from the body more quickly, which reduces the effectiveness of treating COVID-19. Multiple trials indicate that treatments with corticosteroids enhance clinical trials and decrease mortality in hospitalized patients with COVID-19 with oxygen supplements and lung injury and multisystem organ dysfunction induced by COVID-19 systemic inflammatory response. In contrast, people affected by COVID-19 and hospitalized but do not require oxygen supplements and corticosteroids in these patients do not show any improvement, which may harm them. No data support the use of corticosteroids in non-hospitalized patients.

What Is the Relation Between Anabolic Steroids and COVID-19?

Athletes and bodybuilders widely abuse anabolic steroids to enhance their appearance and performance. Regular use of anabolic steroids alters the immune system and makes the person more susceptible to infections. The use of anabolic steroids acts as a risk factor for COVID-19. A study shows current steroid use increases the chance of COVID-19 infections.

What Are the Recommendations for Hospitalized and Non-hospitalized Adults With COVID-19?

1. For Non-hospitalized Adults:

Non-hospitalized patients with mild to moderate COVID-19 infections should be initiated with symptom management. With patients at a high risk of severe infection, antiviral medications are recommended to decrease the risk of hospitalization or death. Therapeutic management aims to prevent the infection from worsening, leading to hospitalization or death. Many factors are involved in selecting the best treatment for a patient; these include:

• The availability of treatment and the efficacy of the treatment.

• The availability of administering parenteral medications.

• The potential for drug-drug interaction.

• Pregnancy status.

• Time for symptom onset.

The COVID-19 treatment guidelines panel does not have sufficient evidence to recommend inhaling corticosteroids to treat COVID-19. Patients with COVID-19 infection who are recommended Dexamethasone or corticosteroids should be continued as prescribed by the doctor.

2. For Hospitalized Adults:

Patients at high risk of progressing to worse or more severe conditions benefit from antiviral therapy. Remdesivir has been approved by the FDA (food and drug administration) for treating COVID-19 infections, even for those who do not require supplemental oxygen. Remdesivir is prescribed for five days or until discharge, whichever comes first.

What Is the Role of Systemic Corticosteroids in Patients With COVID-19?

• Non-hospitalized Patients:

There is no supported data for using systemic corticosteroids by non-hospitalized patients with COVID-19 infection. Therefore, the effect and safety of using systemic corticosteroids are not established. Systemic corticosteroids are associated with many adverse effects, such as hyperglycemia, neuropsychiatric symptoms, secondary infections, etc.

• Hospitalized Patients:

The recovery trial was performed by recommending Dexamethasone six milligrams daily along with standard care or standard care for ten days. The mortality rate on 28 days has decreased in the population who received Dexamethasone than those who received special care alone. Dexamethasone showed benefits in patients who required oxygen supplements, and no benefits were seen in patients who did not require any oxygen supplements.

What Is the Dosage of Dexamethasone Administered?

Many studies and research have been performed based on the dosage of Dexamethasone. Finally, the panel recommended a 6 mg dosage of Dexamethasone once daily. An analysis conducted during the COVID steroid two trial suggests a 12 mg dose of Dexamethasone as it benefits the patients who require a high level of respiratory support. There is no data regarding the safety and efficacy of lower or higher doses of corticosteroids in combination with other immunomodulators in treating COVID-19.

What Is a Combination Immunomodulator Therapy?

Systemic corticosteroids, combined with other agents, are known to have clinical benefits in hospitalized patients with COVID-19 infections, especially with initial critical illness or signs of systemic inflammation.

What Are the Systemic Corticosteroids Used Other Than Dexamethasone?

Based on the available scientific evidence, the panel has concluded the following:

• If Dexamethasone is unavailable, glucocorticoids, such as Prednisone, Methylprednisolone, and Hydrocortisone, can be used as an alternative.

• The dosages of these drugs are:

• Prednisone - 40 mg.

• Methylprednisolone - 32 mg.

• Hydrocortisone - 160 mg.

• Half-life, duration of action, and frequency of administration differ among corticosteroids. There are three types:

• Long-acting corticosteroids - Dexamethasone, whose half-life is 36 to 72 hours, is administered to patients once daily.

• Intermediate-acting corticosteroids - Prednisone and Methylprednisolone with 12 to 36 hours of half-life, which is administered once daily or in two divided doses daily.

• Short-acting corticosteroids - Hydrocortisone with 8-12 hours of half-life, with two to four divided doses daily.

• Hydrocortisone is usually used to treat septic shock in patients with COVID-19 infections.

What Is the Use of Inhaled Corticosteroids in COVID-19 Patients?

Inhaled corticosteroids are effective therapeutic agents that target anti-inflammatory effects on the lungs. Some of these corticosteroids prevent the viral replication of SARS CoV-2 and down-regulate the receptor expression for cell entry.

What Are the Adverse Effects and Drug-Drug Interactions of Steroids in COVID-19 Patients?

• The doctors should monitor the patients receiving Dexamethasone closely, as it causes many adverse effects like hyperglycemia (high blood sugar), secondary infections, psychiatric effects, or avascular necrosis (poor blood flow).

• Oral candidiasis (fungal infection) develops in patients receiving inhaled corticosteroids.

• Fungal infections like mucormycosis, aspergillosis, and reactivation of latent infections such as hepatitis B, tuberculosis, etc., can be caused by systemic corticosteroids.

• Treatment with Tocilizumab and corticosteroids results in severe strongyloidiasis (a disease caused by nematode) in patients with COVID-19 infection.

• The risk of secondary infections increases with systemic corticosteroids and other immunosuppressants.

• Dexamethasone is a cytochrome P450 (CYP) inducer that reduces the concentration and potential of concomitant medications.

• In pregnant women, a short course of Betamethasone or Dexamethasone, known to cross the placenta, decreases the complications of preterm delivery.

Conclusion

Steroids treat various conditions, reducing inflammation and suppressing the immune system. Taking regular steroids in higher doses can increase the risk of COVID-19 infection. Dexamethasone and other corticosteroids are known to treat patients with COVID-19 infection, but in certain cases, they do not provide any benefits and may even worsen the situation. So before intake of any steroids, doctor consultation is recommended.