4. Discussion:
The treatment approach for severe COVID-19 patients is facing dual
challenges. First one is to suppress the hyper-inflammatory responses
and cytokine storm while other one is the viral clearance (27). This
foremost theory hypothesizes that corticosteroids could be used to
alleviate the ”cytokine storm” and its lethal consequences. In a
systematic review of twenty-two studies, Judith VP et al quantified the
effect of corticosteroids on death rate in COVID-19 patients. (17) The
results showed that corticosteroids therapy significantly reduced
short-term mortality in the COVID-19 patients. (17) Furthermore,
meta-analysis of 7 RCTs involving 1703 disparagingly ill COVID-19
patients also revealed that systemic corticosteroids therapy reduced
28-day mortality when compared to standard care (28). The RECOVERYtrial
found that dexamethasone therapy reduced 28-day mortality in individuals
requiring oxygen therapy or mechanical ventilation as compared to
standard care. (7)
Our systematic review and meta-analysis comprised 28 cohorts and 10 RCTs
for investigating the outcome of corticosteroids treatment on the
mortality in COVID-19 patients. Despite the fact that the several
randomized trials found that corticosteroids medication was related to
decreased mortality in COVID-19 patients, we were unable to find the
similar result in our meta-analysis, having sample size 89053 patients.
Our study found that corticosteroids therapy didn’tavert mortality in
the COVID-19 patients, but it has increased the death in the COVID-19
patients as compared to usual care. Furthermore, we also found that both
methylprednisolone and dexamethasone showed the higher mortality in the
COVID-19 patients as compared to usual care. However, there was no
significant difference found in the mortality with respect to treatment
of specific corticosteroid including methylprednisolone and
dexamethasone.
The possible reasons may be considered for increasing the mortality with
corticosteroid therapy like initiation of corticosteroid therapy in
early stage of viral infection and higher dosage of corticosteroids,
which delay the viral clearance and secondary infections. Consistent
toour findings, the results of other meta-analysis on steroid treatment
in COVID-19 patients showed the delay in viral clearance and enhance the
mortality as compared to standard therapy (29). Similar manner, another
propensity score-based analysis study found that corticosteroids use
significantly increased the period of hospital stay and majority of
patients progress to more deteriorated critical conditions compared to
the standard therapy (30). Similarly, Li et al. described a
significantly longer hospital stay in COVID-19 patients who treated with
corticosteroids compared to standard care treatment(31). Furthermore,
patients who received corticosteroids for more than five days required a
extended course of chemotherapeutic agents as compared to patients who
received short-term treatment for 3–5 days (31). Multi-organ
malfunction is much more likely in critically sick COVID-19 patientswho
underwent corticosteroid treatment, according to Lu et al., and each
ten-mg increase in dosage was linked with an extra four percent
mortality risk(32). Furthermore, another meta-analysis found that giving
corticosteroids to patients with influenza increased death and
hospital-acquired infections(33). In a comprehensive evaluation of
influenza pneumonia, glucocorticoid medication was found to be related
with an increased risk of death, length of stay in the critical care
unitand risk of secondary infections(33). According to a meta-analysis
of SARS, MERS and COVID-19, systemic glucocorticoids are not useful in
lowering mortality (34). In meta-analysis of observational studies and
RCT, Tlayjeh et al. reported that corticosteroids therapy was not
associated with a reduction in short-term mortality but may be
associated with a delay in viral clearance in patients hospitalized with
COVID-19. (35) Similarly, WangJ also reported that corticosteroid use in
COVID-19 patients delayed viral clearance and didn’t improve survival
(36) .