Steroid treatment for COVID-19: Suitable dose and patients.

Coronavirus disease 2019 (COVID-19) had the largest worldwide use of steroid treatment in the history of medicine. Although the use of steroids in COVID-19 started with the start of the pandemic, it became rampant after the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial.[1] This trial reported that as compared to usual care, low-dose dexamethasone treatment (6 mg daily for 10 days) reduced mortality by one-third in patients receiving mechanical ventilation (29.3% vs 41.4%; rate ratio: 0.64 [95% CI, 0.51–0.81]) and by one-fifth in patients receiving supplemental oxygen (23.3% vs 26.2%; 0.82 [95% CI, 0.72–0.94]) but had no benefit among patients not receiving respiratory support (1.19 [95% CI, 0.91–1.55]). The findings of this trial were further confirmed by a meta-analysis[2], and thereafter, steroids became the first-line treatment of almost all COVID-19 guidelines worldwide. However, many centres, particularly in India and other Asian countries, started using higher doses including pulse dose of steroids for almost all hospitalised patients whether hypoxaemic or non-hypoxaemic that could be an underlying cause of increased mortality in the disease.[3] More recently, the RECOVERY-II trial reported that compared to low-dose dexamethasone (6 mg daily for 10 days), high-dose dexamethasone (20 mg daily for 5 days followed by 10 mg daily for 5 days) was associated with increased mortality (19% vs 12%; 1.59 [95% CI 1.20–2.10]) and non-COVID-19 pneumonia (10% vs 6%, absolute increased risk: 3.7% [95% CI: 0·7–6·6]) in COVID-19 patients with clinical hypoxia receiving simple or no oxygen.[4] However, cause of non-COVID pneumonia associated with the use of high dose of steroids was not clarified by this trial. As per our recent meta-analysis, steroids impair host immunity and make them vulnerable to secondary infections, including COVID-19-associated pulmonary aspergillosis (CAPA), which may be the underlying cause of non-COVID-19 pneumonia associated with high-dose steroid treatment in these patients.[5] The RECOVERY-II trial has further reported an association of high-dose steroid treatment with hyperglycaemia (22% vs 14%; absolute difference: 7.4% [95% CI: 3.2–11.5]), which is also a well-recognised risk factor for CAPA.[6] The development of CAPA or other secondary infections and hyperglycaemia represents high mortality complications of COVID-19 and may be responsible for increased mortality in patients treated with high-dose steroids.[6,7] Other recent publications have reported that prolonged steroid treatment (i.e., for >10 days) in COVID-19 patients is also associated with an increased risk of CAPA.[8] Furthermore, the injudicious use of steroids is also associated with COVID-19-associated mucormycosis (CAM). A large multicentre case–control study on CAM across 25 hospitals in India concluded that cumulative glucocorticoid dose (odds ratio [OR]: 1.006, 95% CI: 1.004-1.007), diabetes mellitus [OR: 6.72, 95% CI: 5.45–8.28] and diabetic ketoacidosis during COVID-19 [OR: 4.41, 95% CI: 2.03–9.60]) were important controllable risk factors for CAM outbreak.[9,10] So, the use of steroids in non-hypoxaemic patients should be highly discouraged to prevent secondary infections including aspergillosis and mucormycosis. Similarly, high dose or prolonged use of steroids should be avoided as it can augment mortality by inducing CAPA, CAM, hyperglycaemia and/or other adverse effects. Sometimes, steroids are unnecessarily used to chase unusual inflammatory markers or other non-genuine indications without the actual presence of persistent hypoxia. Hypoxia too must be properly documented, not just one or two low readings of pulse oximeter, which may sometimes be erroneous. In conclusion, to achieve clinical benefit and minimise hazardous effects, the suitable steroid treatment of COVID-19 is judicious use of low doses of steroids for a limited period only, and suitable COVID-19 patients for this steroid treatment are only those having well defined hypoxemia. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.