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.