Dr. Parjam ZolfaghariHIND MOHAMMED ABDULAZIZ ALASSAF2022-05-302022-05-30https://drepo.sdl.edu.sa/handle/20.500.14154/51532ABSTRACT Background COVID-19 is a rapidly spreading disease that is considered a global threat, and it has been declared as a pandemic by the WHO. SARS-CoV-2 transmission happens from person to person via droplets produced by sneezing and coughing. At the time of this writing, there are more than 212,328,733 confirmed cases of COVID-19 and 4,438,511 million reported deaths. Thus, exploring the causes of mortality and advances in innovative treatment development is critical at this time, as countries are eager to find a cure. Clinicians caring for patients have observed that SARS-CoV-2 induced exuberant inflammatory responses contribute to the pathogenesis of ARDS and multi-organ failure leading to death, which is found in the vast majority of fatal cases. However, various studies have suggested the use of tocilizumab (TCZ) to treat patients with COVID-19 as it works to diminish the cytokine storms. TCZ is an IL-6 inhibitor that affects signal transmission to achieve gene expression blockade. As a result, inhibiting this interaction can help reduce systemic inflammation in immunological diseases. Aim The purpose of this study is to examine the effectiveness of Tocilizumab (TCZ) in treating adult patients with COVID-19 in reducing the need of NIV and IMV, and reducing the mortality rate. Furthermore, to determine whether the use of TCZ in SARS-CoV-2 patients associated with serious adverse events (SAEs). Methods This systematic review presents a meta-analyses of randomized controlled trials (RCTs) on the use of TCZ to treat SARS-CoV-2 patients compared to standard care or placebo, from 2019 to 31 June 2021 by using Electronic databases PubMed, EMBASE, and Cochrane Library. The primary outcomes were requirement for non-invasive or invasive mechanical ventilator, and mortality by day 28. While secondary outcomes was treatment related adverse events. Meta-analysis was conducted using random effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Page 3 of 46 Results Eight studies RCTs published between 2020 and 2021 met inclusion criteria. With a total of 5,749 adult participants who were randomly assigned to control group (n=2,733), and TCZ group (n= 3,016). Of the 5,749 patients, 3849 were males (67%). The pooled analysis of unadjusted RRs for these 8 RCTs for overall mortality at day 28, shows that the use of tocilizumab associated with a survival benefit. (RR 0.91, 95% CI 0.82–1.00, P = 0.05). In term of requirements for NIV or IMV, using NIV or IMV is 0.87 times the risk of using NIV or IMV in the control group. (RR 0.87, 95% CI 0.51–1.47, P= 0.004). Regarding the adverse events, pooled analysis of unadjusted Odds ratio for 7 RCTs, shows that there was no significant difference between the TCZ and control group (odds ratio 1.11, 95% CI 0.83–1.50, I2 = 35%, P = 0.48). The odds of experiencing adverse events is 1.11 times the odds of experiencing adverse event in control group. Furthermore, there was no significant difference in the odds of experiencing serious adverse events, infections, and respiratory disorder. Conclusion The results of using TCZ in COVID-19 patients in this systematic review and meta-analysis showed that the use of survival benefits reduces mortality and decreases the requirements for NIV or IMV. Regarding the adverse events, there was no significant difference between the TCZ and control group; there was no significant difference in the odds of experiencing severe adverse events, infections, and respiratory disorders.en