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) .