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Dear Editor, We would like to thank Dr Kounis and his colleagues for taking interest in our paper and providing their valuable opinion.[1] In his letter, Dr Kounis highlights the possible use of corticosteroids in mild COVID-19. Google Scholar Crossref Search ADS PubMed WorldCat 6 Sarda R, Swain S, Ray A, Wig N. COVID-19 associated mucormycosis and evolving evidence. [Extracted from the article]

Background Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). Aim To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients. Design A systematic review and meta-analysis. Methods Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28–30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses. Results Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28–30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82–0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74–1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35–0.93). Conclusion The treatment with TCZ reduces 28–30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19. [ABSTRACT FROM AUTHOR]

Although additional experiments and clinical studies are required to confirm this hypothesis, we hope that hydrogen therapy would provide an emerging and good option for the currently limited prevention and treatment strategy of COVID-19. High IL-6 level had also been found closely correlated with the incidence of detectable serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and the vital signs of coronavirus disease 2019 (COVID-19) patients. 7,8 We hypothesize that hydrogen therapy may be as an effective and novel adjuvant treatment against COVID-19, and exhibit the beneficial potential to prevent COVID-19-associated cytokine storm and multiple organ damage through following multiple mechanisms. [Extracted from the article]