Abstract: review of published meta-analyses iew ed Does colchicine reduce mortality in patients with COVID-19 clinical syndrome? an umbrella Mohammed I Danjuma 1,2,3, Rana Sayed4, Maryam Aboughalia4, Aseel Hassona4, Basant Selim Elsayed4, Mohamed Elshafei5, Abdelnaser Elzouki1,2,4 1. Department of Internal Medicine, Hamad Medical Corporation, Doha Qatar ev 2. Department of Internal Medicine, Weill Cornell College of Medicine, New York, and Doha Qatar 3. NHS Grampian (Dr Grays Hospital) er r 4. Department of Internal Medicine, Qatar University College of Medicine rin tn ot pe 5. Department of Pharmacy, Hamad Medical Corporation, Doha Qatar Corresponding author: Dr. Mohammed Ibn-Mas’ud Danjuma ep Consultant Physician and Clinical Pharmacologist Department of Internal Medicine, Weill Cornell College of Medicine New York and Doha Qatar Pr Email: mdanjuma21@gmail.com; mdanjuma@hamad.qa 1 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4447127 iew ed Abstract Background Despite significant improvements in both treatment and prevention strategies, as well as multiple commissioned reviews, there remains uncertainty regarding the survival benefit of repurposed drugs such as colchicine in patients with Covid-19 clinical syndrome. ev Methods: In this umbrella review, we carried out a comprehensive search of PubMed, EMBASE, Cochrane Database of Systematic Reviews, Science Citation Index, and the Database of er r Abstracts of Reviews of Effectiveness between 1st January 2020 and 31st January 2023 for systematic reviews and meta-analyses evaluating the mortality-reducing benefits of colchicine in patients with Covid-19. This was to ascertain the exact relationship between colchicine pe exposure and mortality outcomes in these cohorts of patients. We utilized A Measurement Tool to Assess systematic Reviews-2 (AMSTAR-2) to conduct an exhaustive methodological quality and risk of bias assessment of the included reviews. ot Results: We included eighteen meta-analyses (n = 199,932 participants) in this umbrella review. tn Colchicine exposure was associated with an overall reduction of about 35% in the risk of mortality (odds ratio 0.68, confidence interval [CI] 0.58-0.78; I2 = 94%, p = 0.001). Further examination of pooled estimates of mortality outcomes by the quality effects model (corrected rin for the methodological quality and risk of bias of the constituent reviews) reported similar point estimates (OR 0.73; CI 0.59 to 0.91; I2 = 94%). ep Conclusion: In a pooled umbrella evaluation of published meta-analyses of Covid-19 patient cohorts, exposure to colchicine was associated with a reduction in overall mortality. Although it remains Pr uncertain if this effect could potentially be attenuated or augmented by Covid-19 vaccination. PROSPERO Registration number: CRD42023397246. 2 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4447127 iew ed Key words: COVID-19; Colchicine; Meta-analysis; Mortality; Umbrella Background Successful immunization with a variety of approved Coronavirus Disease 2019 (COVID-19) vaccines has significantly contributed to containing both the spread and the adverse consequences of this nascent infection. However, the exact role of clinical therapeutics in its management is still evolving. Since the onset of the COVID-19 pandemic, repurposing of drugs ev with..