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CORTICOSTEROIDS (glucocorticoids)

Corticosteroids are used in long-haul and post vaccine syndrome protocol at low doses for up to 6 weeks while, on occasion in severe, acute COVID-19 it is used at higher doses and for shorter durations. Although corticosteroids use in COVID-19 patients with oxygen needs is the standard of care worldwide, their use in post-COVID and post-Vaccine syndromes are not based on controlled trials and is instead based on our evolving knowledge of the pathophysiology of the syndromes, combined with positive case series and rapidly developing clinical experience among a widening network of Dr. Kory’s colleagues.

Administration: Adult

Administer after meals or with food or milk to decrease GI upset. May administer antacids between meals to help prevent peptic ulcers.

Adrenal suppression (tertiary adrenal insufficiency) may occur with glucocorticoids, including prednisone, and results from inadequate stimulation of the adrenal glands. Prednisone-induced adrenal insufficiency may last months. Adrenal crisis is a life-threatening emergency and the result of secondary adrenal insufficiency that can present like a hypotensive shock state (Ref).

Mechanism: Dose and time-related; occurs due to lack of or diminished cortisol production, which is decreased by the adrenal gland. Exogenous glucocorticoids produce a similar negative feedback mechanism as endogenous cortisol, causing a subsequent decrease in ACTH secretion; thus, cortisol production is suppressed resulting in adrenal insufficiency. In times of stress (critical illness, trauma, or surgery), the body requires stress doses in patients taking prednisone chronically (Ref).

Onset: Varied; acute (minutes after administration) and/or chronic (2 to 20 hours to days) (Ref). Chronic prednisone use does not allow for the HPA axis to recover quickly (Ref).

Risk factors:

  • High doses for prolonged periods: Although some patients may become HPA suppressed with lower doses or briefer exposure, some experts consider HPA-axis suppression likely in any adult receiving >20 mg/day (daytime dosing) or ≥5 mg per 24 hours (evening or night dosing) for >3 weeks or with cushingoid appearance (Furst 2019b, Joseph 2016).
  • Potency of glucocorticoids (Dineen 2019)
  • Abrupt withdrawal of prednisone (Dineen 2019)
  • Concurrent interacting medications (eg, carbamazepine, St John’s wort, mitotane, rifampicin, itraconazole, diltiazem) (Ref)
  • History of previous adrenal crisis (Ref)
  • Use of glucocorticoid therapy delivered by various routes of administration (eg, topical, inhaled) (Ref)

Cardiovascular effects

Prednisone has potent cardiovascular effects which include hypertension, dyslipidemia, fluid retention, electrolyte disturbances (decreased serum potassium, sodium retention), and arrhythmias (from rare cases of bradycardia to more common reports of atrial fibrillation). Fluid retention can worsen cardiac failure in some patients because of its mineralocorticoid properties

CNS and psychiatric/behavioral effects

Glucocorticoids, including prednisone, may cause a myriad of CNS and psychiatric/behavioral adverse reactions. Patients may develop apathy or depression. More commonly, patients develop excitatory psychiatric disturbance (including agitation, anxiety, distractibility, fear, hypomania, insomnia, irritability, lethargy, labile mood, pressured speech, restlessness, and tearfulness


Glucocorticoids, including prednisone, may provoke new-onset hyperglycemia in patients without a history of diabetes and may worsen hyperglycemia in patients with diabetes mellitus. Certain patient populations (eg, transplant, cancer, chronic rheumatologic conditions) are at particular risk due to medication combinations


Glucocorticoids, including prednisone, have immunosuppressive and anti-inflammatory effects that are reversible with discontinuation. Infection may occur after prolonged use, including Pneumocystis jirovecii pneumonia (PJP), herpes zoster, tuberculosis, and other more common bacterial infections

Neuromuscular & skeletal effects

Glucocorticoid (including prednisone)-induced neuromuscular and skeletal effects can take the form of various pathologies in patients ranging from osteoporosis and vertebral compression fracture to myopathy to osteonecrosis in adult and pediatric patients. Vertebral fractures are the most common glucocorticoid-related fracture. Myopathies can also occur secondary to direct skeletal muscle catabolism (Ref). Acute steroid myopathy is rare

Ocular effects

Glucocorticoid (including prednisone)-induced ocular effects may include increased intraocular pressure (IOP), glaucoma (open-angle), and subcapsular posterior cataract in adult and pediatric patients

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Bradycardia, cardiac failure (in susceptible patients), cardiomegaly, circulatory shock, edema, hypertrophic cardiomyopathy (premature infants), myocardial rupture (after recent myocardial infarction), syncope, tachycardia, thrombophlebitis, vasculitis

Dermatologic: Acne vulgaris, allergic dermatitis, atrophic striae, diaphoresis, facial erythema, hyperpigmentation, hypopigmentation, skin atrophy, skin rash, thinning hair (scalp), urticaria

Endocrine & metabolic: Decreased serum potassium, fluid retention, growth retardation (children), hirsutism, hypokalemic alkalosis, menstrual disease, negative nitrogen balance (due to protein catabolism), sodium retention, weight gain

Gastrointestinal: Hiccups, increased appetite, nausea

Genitourinary: Asthenospermia, oligospermia

Hematologic & oncologic: Bruise, petechia

Hepatic: Hepatomegaly, increased serum transaminases

Hypersensitivity: Angioedema

Infection: Sterile abscess

Nervous system: Abnormal sensory symptoms, arachnoiditis, headache, increased intracranial pressure (with papilledema), malaise, meningitis, myasthenia, neuritis, neuropathy, paraplegia, paresthesia, seizure, vertigo

Neuromuscular & skeletal: Charcot arthropathy

Respiratory: Pulmonary edema

Miscellaneous: Wound healing impairment

Drug Interactions of corticosteroids can be checked here: