The effect of Nigella sativa on the risk of mortality in patients with COVID‐19: A systematic review and meta‐analysis of randomized trials
Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan
Phytotherapy Research, doi:10.1002/ptr.7743
The coronavirus disease 2019 (COVID-19) pandemic has challenged the healthcare systems given the uncontrolled spread and high mortality rate of patients with severe course of illness. In addition, anger and frustration with the pandemic are widespread due to the negative impacts of COVID-19 on social, mental, and physical well-being. Therefore, the hunt for safe and effective treatment for COVID-19 should be continued to wipe out this deadly disease. To this end, supplemental herbal remedies are being investigated as a potential treatment for COVID-19 due to their abundance of physiologically active components. Owing to its wide range of pharmacological actions, including its antiinflammatory, anti-viral, and immunomodulatory effects, Nigella sativa is specifically recommended as a possible phytomedicine for COVID-19 (Khazdair, Ghafari, & Sadeghi, 2021). It is a medicinal herb commonly referred to as "Black Cumin," and it is one of the most treasured nutrient-rich herbs in history worldwide. Even before the pandemic, N. sativa has been demonstrated to possess antiviral activities against a wide range of viruses (Koshak & Koshak, 2020) . Also, by producing several cellular mediators and immunological responses to combat infections, N. sativa has been demonstrated to possess immunostimulant effects (Gholamnezhad, Boskabady, & Hosseini, 2014; Majdalawieh & Fayyad, 2015) . In addition, by lowering proinflammatory mediators, N. sativa has also displayed antiinflammatory properties in inflammatory diseases (Bordoni et al., 2019; Hadi, Kheirouri, Alizadeh, Khabbazi, & Hosseini, 2016) . Previously in this journal, the randomized trial reported by Karimi et al. (2021) showed N. sativa accelerated the clinical recovery of patients with COVID-19. Nevertheless, the ability of this herbal remedy to reduce the risk of mortality in patients with COVID-19 may have been overlooked. Several randomized trials have been performed to investigate the effects of N. sativa on mortality reduction in patients with COVID-19. We aimed to summarize their overall mortality benefits in a systematic review and meta-analysis.
mediated immune responses (Salem, 2005) . On the other hand, antiviral effects of N. sativa against SARS-CoV-2 have been indicated by the efficient binding of the constituents of N. sativa such as α-hederin, thymohydroquinone, and thymoquinone to angiotensin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, in molecular docking analyses, and thus preventing viral entry into host cells (Jakhmola Mani, Sehgal, Dogra, Saxena, & Pande Katare, 2022) . Nevertheless, the safety of N. sativa in patients with COVID-19 should be further investigated since the included trials did not report on safety outcomes. Furthermore, while no major safety concerns are reported in the literature with the consumption of N. sativa, some minor adverse effects, including nausea, bloating, and burning sensation, have been observed with the administration of N. sativa seed oil in functional dyspeptic patients, as well as a slight increase in liver enzymes (Tavakkoli, Mahdian, Razavi, & Hosseinzadeh, 2017) . Several limitations should be considered while reviewing the findings of our study. Firstly, our systematic review and metaanalysis included only three randomized trials, where some trials are with methodological flaws. Further large-scale, well-planned trials are required to confirm our findings. Nevertheless, we believe our findings should best be interpreted as an initial lead to guide efforts for more investigations of the use of N. sativa in patients with COVID-19 to..
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