Clinical Consideration of Glucocorticoids in COVID-19

Abstract

Severe infection of COVID-19 is characterized by an excessive inflammatory response in a form of a storm of proinflammatory cytokines leading to severe lung injury and life-threatening acute respiratory distress syndrome (ARDS). The use of glucocorticoids (GCs) in COVID-19 associated pneumonia and cytokine storm is debatable. A systematic review and meta-analysis were conducted to evaluate the safety and efficacy of GCs in COVID-19, SARS-CoV, and MERSCoV infections reporting an insignificant association between GCs use and mortality rate, length of hospital stay, ICU admission and need for mechanical ventilation. Moreover, the use of GCs in pneumonia associated with SARS-CoV or MERS-CoV did not significantly improve mortality rate. However, GCs are recommended in certain circumstances and comorbidities associated with viral pneumonia such as septic shock, severe ARDS, asthma, and chronic obstructive pulmonary disease (COPD). Recently, the RECOVERY trial; a randomized, controlled, open-labeled, adaptive clinical trial (n 1⁄4 2104) had released the preliminary results displaying that low dose of dexamethasone was associated with a reduction in mortality rate by a third in mechanically ventilated patients, by a fifth in patients on oxygen supply, and no benefits were observed in patients without oxygen support. Due to the differences in the mean age (a key prognostic factor) between the randomized groups, age adjustment was performed to account for this variance; however, the conclusion before and after age adjustment did not alter substantially. Thus, dexamethasone could be used with small doses for a short duration in critically ill patients who are intubated and those patients whose symptoms lasted for more than 7 days than those with recent onset of symptoms. Furthermore, dexamethasone would have the potential to minimize the damaging effect of cytokines and limit its production; however, it would inhibit antibodies production and consequently increases the viral load. To date, GCs are used frequently in COVID-19 protocols based on the urgent need to reduce the hyper-inflammatory response associated with severe COVID-19 infection which unlike that of the classical ARDS. In common practice, the widely used intravenous GCs in clinical settings are dexamethasone, hydrocortisone, and methylprednisolone. Recently, a clinical trial has reported a significant benefit of dexamethasone administration in critically ill patients who were mechanically ventilated or on respiratory support and dexamethasone was administrated by oral or intravenous route (6 mg/day, for a duration of 10 days). In addition, hydrocortisone has been used as a shock reversal in severe cases of COVID-19 with refractory shock which administrated by intravenous route either continuous infusion or intermittent (200 mg/day) with duration based on the clinical response. Moreover, based on a retrospective study (n 1⁄4 201) conducted in Wuhan, China, methylprednisolone was used in COVID-19 patients with ARDS and associated with a decline in the mortality rate.A short course protocol of methylprednisolone was conducted for COVID-19 patients with moderate to severe infection (0.5-1 mg/kg/day in 2 divided doses for a duration of 3 days) and associated with a reduction in mortality and hospital stay. Steroids are associated with serious adverse effects related to the dose and duration of exposure such as endocrine complications, myopathy, osteoporosis, Cushing’s syndrome, immunosuppression and psychiatric effects. Furthermore, blood glucose levels should be monitored carefully with steroid administration because GCs induced hyperglycemia. Also diabetic patients with COVID-19 are at high risk for more complications that increase mortality. Thus, hyperglycemia should be managed vigorously to an optimum blood glucose level. In addition, sodium and potassium serum levels should be monitored because GCs may cause hypernatremia and hypokalemia due to mineralocorticoid effects of many steroids. Tapering of GCs is necessary to avoid the risk of adrenal insufficiency. Moreover, risk of gastrointestinal (GI) manifestations such as GI bleeding, anorexia, abdominal pain could be observed and proton pump inhibitors are recommended. In conclusion, the use of steroids in COVID-19 associated pneumonia is controversial and data from literature does not fully support the routine use of steroids. However, we recommend the early administration of methylprednisolone in