The effect of curcumin on the risk of mortality in patients with COVID-19: A systematic review and meta-analysis of randomized trials

The coronavirus disease 2019 (COVID-19) pandemic is far from bygone, with the emergence of newer variations of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the worldwide vaccine rollout has progressed at a breakneck pace, the hunt for new safe, effective, and targeted treatments should continue in parallel due to the frequent occurrence of breakthrough cases. Curcumin is one such natural polyphenolic compound with multiple benefits, including antiviral, anti-inflammatory, anticoagulant, antiplatelet, and cytoprotective, which have been demonstrated to be advantageous in reducing the progression of several inflammatory illnesses (Rattis, Ramos, & Celes, 2021). The aforementioned effects have made curcumin one of the potential treatment options for patients with COVID-19. Since the pathophysiology of COVID-19 is known to involve life-threatening inflammatory reactions, cytokine storms, and coagulopathy, curcumin can be advantageous due to its anti-inflammatory effects via the inhibition of inflammasome formation (Yin et al., 2018). In addition, curcumin also demonstrates antiviral effects via its ability to bind to the viral primary protease (Mpro) enzyme of SARS-CoV-2, which is required for viral replication. Curcumin also prevents viral attachment and passage into the host cell with great potency (Dourado et al., 2021). The ability of curcumin in inhibiting the virus-receptor interaction is in two ways, according to modeling studies: it inhibits both the spike protein and the ACE2 receptor (Manoharan et al., 2020). Previously in this journal, the findings of the randomized trial reported by Hassaniazad et al. (2021) suggest that curcumin can accelerate the recovery of acute inflammatory phase in patients with COVID-19 by modulating inflammatory immune responses. Nevertheless, the mortality benefits of curcumin in patients with COVID-19 were not investigated in the aforementioned trial. Several controlled trials have been performed to validate the mortality benefits of curcumin in patients with COVID-19, and we aimed to summarize their overall efficacy in terms of mortality reduction in a systematic review and meta-analysis.