1. Introduction:
World Health Organization (WHO) reported 505,817,953 confirmed COVID-19 cases and 6,213,876 fatality from COVID-19till April 22, 2022 (1). COVID-19 infection can cause infection without any symptoms, moderate upper respiratory tract sickness, severe pneumonia condition, respiratory failure and even death (2). In severe COVID-19 infection, symptoms deteriorate and become hypoxic after four to seven days and can advance to acute respiratory distress syndrome (ARDS) between eight and twelve days (3). Immune-mediated cascades including increased proinflammatory cytokines levels and cytokine storm, rather than virus-induced damage, are equally important in the pathophysiology of multiple organ damage and mortality (4). Therefore, corticosteroid therapy was proposed to suppress the immune-mediated cascades and cytokine storm-related complications and mortality in COVID-19 (5,6). Therefore, numerous of observational studies and randomized controlled trials (RCT) to investigate the effect of corticosteroids therapy in COVID-19 have been initiated and reported.
Recently, the RECOVERY study reported the rationale for the corticosteroid therapy in severe COVID-19 patients (7). As per initial results from the RECOVERY study, dexamethasone reduced 28-daysfatality in severe COVID-19 patients (7). Multiple randomized trials have been found that systemic corticosteroids therapy improve clinical results and lowers fatality in COVID-19 hospitalized patients thoseneedof oxygen supplement(7–16). Based on results from these clinical trials, WHO advised to utilization of corticosteroids for the management of severe COVID-19 patients (17). Furthermore, the recent global Surviving Sepsis Guideline suggests to use steroids in the severe COVID-19 patients those on mechanical ventilation support with ARDS (18).
In contrary, the Centers for Disease Control and Prevention (CDC), United States has not been specifically advice either for or against the utilization of corticosteroids in COVID-19. for immunological regulation (20). It has been reported that corticosteroids usage causes the delay in viral RNA clearance in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MARS)(19). A recent study also indicated that corticosteroid therapy started at high dose or early stage (less than three days) of infection in critical COVID-19 patients delayed viral clearance and increased the risk of 28-days mortality (20). The possible cause might be weakening of the immune response by corticosteroid therapy. The weakening of patients’ immune systems from corticosteroid therapy leads to rarely occurring fungal infections (e.g. aspergillosis, mucormycosis), relapsing of dormant infections (e.g. herpesvirus infections, strongyloidiasis, hepatitis B virus infection, tuberculosis) and respiratory failure (21–25). Recent study reported that corticosteroids use in SARS patients has been associated to significant consequences such as avascular necrosis, diabetes and psychosis. (19,26)
The results of multiple RCTs and observational studies are very diverse and contradictory, which arising difficulty in the clinical decision-making. Furthermore, these studies were performed with limited sample size. Therefore, there is need to review available studies with greater statistical power for concrete conclusion in relation to utilization of corticosteroids in the COVID-19 patients. The objective of this study is to assess relationship between corticosteroids therapy usage and mortality in the COVID 19 patients by a systematic review and meta-analysis of RCT and observational cohort studies.