Annals of Medicine and Surgery | 2021
When to call it off: Defining the role of low-dose corticosteroids in thwarting the progression of non-severe COVID-19
Abstract
The coronavirus disease 2019 (COVID-19) continues to wreak havoc, culminating in soaring morbidity and mortality worldwide. To date, a plethora of pharmaceutical regimens has been employed in the treatment of the infection, but management of the ailment still remains largely supportive. In addition to antivirals such as remdesivir, azithromycin and tocilizumab also remain the cornerstone of current therapeutic management. Recent research has divulged that the exorbitantly high fatality and morbidity rates associated with COVID-19 can be attributed, in part, to an aberrant and dysregulated immune response that ensues secondary to the cytokine storm observed in COVID-19 [1]. Corticosteroids have traditionally remained exceedingly imperative in the management of hyperinflammatory states. Owing to their potent anti-inflammatory properties, corticosteroids have remained at the epicentre of a therapeutic conundrum surrounding the optimal management of COVID-19. To this end, the RECOVERY trial yielded conspicuous evidence that the administration of dexamethasone in critically-ill COVID-19 patients was associated with ameliorated disease outcomes [2]. Furthermore, several randomised controlled trials have also corroborated the findings of the RECOVERY trial, demonstrating significantly improved outcomes in critically-ill COVID-19 patients treated with corticosteroids [3]. In the aftermath of these findings, the US National Institute of Health (NIH) vouches for the uptake of dexamethasone in patients with severe COVID-19 [4]. In the same vain, the WHO recommends the use of systemic corticosteroids in patients with severe manifestations of COVID-19 [5]. However, the WHO advises against the use of steroids in non-critically ill patients [5]. Nevertheless, there is paucity of data that evaluates the efficacy of a low-dose corticosteroid regimen in halting the progression of non-severe COVID-19. Corticosteroids possess anti-inflammatory properties, which can be instrumental in modulating the aberrant, hyperactive immune response that remains a hallmark of COVID-19 [3]. These anti-inflammatory properties aim towards controlling the overdrive in cytokine production by inhibiting the transcription of certain pro-inflammatory cytokines that ultimately foment an esoteric cytokine storm [3]. Interestingly, recent literature has shown that glucocorticoids can indeed reduce inflammatory cell exudation and phagocytosis in the early stages of inflammation, thereby inhibiting excessive proliferation of fibroblasts that is associated with adverse disease outcomes [3]. The landmark RECOVERY trial was the first to demonstrate that the use of corticosteroids in critically-ill COVID-19 patients is indeed associated with reduced all-cause mortality and thus improved disease outcomes [2]. The trial evaluated patients who were hospitalized with a severe COVID-19 infection. Subjects were randomly assigned to either receive a 6 mg dose of once daily dexamethasone, or to receive the usual standard of care alone. The results from the trial divulged a reduced 28-day mortality rate in the dexamethasone group when compared to the non-steroid group (22.9% vs 25.7%, age-adjusted rate ratio = 0.83; 95% confidence interval = 0.75 to 0.93; P < 0.001) [2]. Furthermore, the 28-day mortality decreased from 41.3% to 29.3% in those receiving invasive mechanical ventilation, and from 26.2% to 23.3% in those receiving supplementary oxygen alone. Additional favourable outcomes within the dexamethasone group included shorter hospital stays and reduced progression to ventilation [2]. Contrarily, several studies have demonstrated that corticosteroid use in COVID-19 patients, while beneficial in terms of reducing overall mortality, might indeed be associated with reduced viral clearance and an increased risk of developing secondary infections [6]. Moreover, a number of studies have vouched against the use of corticosteroids in the early phases of COVID-19, citing their immunosuppressive effects, delaying of viral clearance, and numerous complications as evidenced