Abstract: Metabolism Open 8 (2020) 100066 Contents lists available at ScienceDirect Metabolism Open journal homepage: www.journals.elsevier.com/metabolism-open The combination of bromelain and curcumin as an immune-boosting nutraceutical in the prevention of severe COVID-19 Panagiotis Kritis a, 1, Irene Karampela b, *, 1, Styliani Kokoris c, Maria Dalamaga d a Pulmonary and Tuberculous Diseases Private Practice, 27 K. Aitolou, 14121, Neo Iraklio, Athens, Greece Second Department of Critical Care, Attikon General University Hospital, School of Medicine, National and Kapodistrian University of Athens, 1 Rimini Street, 12462, Haidari, Greece c Laboratory of Hematology and Blood Bank Unit, Attikon General University Hospital, School of Medicine, National and Kapodistrian University of Athens, 1 Rimini Street, 12462, Haidari, Greece d Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, 27 Mikras Asias, 11527, Goudi, Athens, Greece b a r t i c l e i n f o a b s t r a c t Article history: Received 10 November 2020 Accepted 11 November 2020 Available online 13 November 2020 The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, while no treatment has been proven effective. COVID-19 pathophysiology involves the activation of three main pathways: the inflammatory, the coagulation and the bradykinin cascades. Here, we highlight for the first time the joint potential therapeutic role of bromelain and curcumin, two well-known nutraceuticals, in the prevention of severe COVID-19. Bromelain (a cysteine protease isolated from the pineapple stem) and curcumin (a natural phenol found in turmeric) exert important immunomodulatory actions interfering in the crucial steps of COVID-19 pathophysiology. Their anti-inflammatory properties include inhibition of transcription factors and subsequent downregulation of proinflammatory mediators. They also present fibrinolytic and anticoagulant properties. Additionally, bromelain inhibits cyclooxygenase and modulates prostaglandins and thromboxane, affecting both inflammation and coagulation, and also hydrolyzes bradykinin. Interestingly, curcumin has been shown in silico studies to prevent entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells as well as viral replication, while a recent experimental study has demonstrated that bromelain may also inhibit viral entry into cells. Notably, bromelain substantially increases the absorption of curcumin after oral administration. To the best of our knowledge, this is the first report highlighting the significance of bromelain and, most importantly, the potential preventive value of the synergistic effects of bromelain and curcumin against severe COVID-19. © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Keywords: Bromelain COVID-19 Curcumin Nutraceuticals SARS-CoV-2 The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been devastating so far, affecting more than 45 million people and causing more than 1 million deaths globally, as of November 2, 2020 [1]. Research efforts in the quest for an effective treatment for the coronavirus disease 2019 (COVID-19) have been fruitless, while our hopes to contain the Abbreviations: ACE2, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019; COX-2, cyclooxygenase-2; NF-kB, nuclear..