Abstract: Received: 12 September 2021 | Revised: 6 March 2022 | Accepted: 5 April 2022 DOI: 10.1111/jcmm.17337 ORIGINAL ARTICLE Effect of ArtemiC in patients with COVID-­19: A Phase II prospective study Elias Hellou1,2,3 | Jameel Mohsin2,3 | Ameer Elemy4 | Fahed Hakim4,5 | Mona Mustafa-­Hellou3,6 | Shadi Hamoud3,6 1 Department of Cardiology, E.M.M.S Hospital, Nazareth, Israel 2 Department of Cardiology, Hillel Yaffe Hospital, Hadera, Israel 3 Rappaport Faculty of Medicine, Technion-­Israel Institute of Technology, Haifa, Israel 4 Victory Department for COVID-­19 Patients, E.M.M.S Hospital, Nazareth, Israel 5 Azrieli Faculty of Medicine, Bar-­Ilan University, Zefat, Israel 6 Department of Internal Medicine E, Rambam Health Care Campus, Haifa, Israel Correspondence Elias Hellou, Department of Cardiology, E.M.M.S Hospital, POB 201, Nazareth ZIP 16000, Israel. Email: Eliasgh@gmail.com Abstract Despite intensive efforts, there is no effective remedy for COVID-­19. Moreover, vaccination efficacy declines over time and may be compromised against new SARS-­CoV-­2 lineages. Therefore, there remains an unmet need for simple, accessible, low-­cost and effective pharmacological anti-­SARS-­CoV-­2 agents. ArtemiC is a medical product comprising artemisinin, curcumin, frankincense and vitamin C, all of which possess anti-­inflammatory and anti-­oxidant properties. The present Phase II placebo-­controlled, double-­blinded, multi-­centred, prospective study evaluated the efficacy and safety of ArtemiC in patients with COVID-­19. The study included 50 hospitalized symptomatic COVID-­19 patients randomized (2:1) to receive ArtemiC or placebo oral spray, twice daily on Days 1 and 2, beside standard care. A physical examination was performed, and vital signs and blood tests were monitored daily until hospital discharge (or Day 15). A PCR assessment of SARS-­CoV-­2 carriage was performed at screening and on last visit. ArtemiC improved NEWS2 in 91% of patients and shortened durations of abnormal SpO2 levels, oxygen supplementation and fever. No treatment-­related adverse events were reported. These findings suggest that ArtemiC curbed deterioration, possibly by limiting cytokine storm of COVID-­19, thus bearing great promise for COVID-­19 patients, particularly those with comorbidities. KEYWORDS ArtemiC, artemisinin, COVID-­19, curcumin, Vitamin C 1 | I NTRO D U C TI O N organs, particularly in aged patients with diabetes, obesity, hypertension, heart failure and respiratory diseases. 2,3 Critically ill cases The coronavirus disease 2019 (COVID-­19) pandemic, which initially are characterized by acute respiratory distress syndrome (ARDS) emerged in Wuhan-­South-­eastern China in 2019, is caused by severe and septic shock, as well as multiple organ dysfunction or failure. 2–­4 acute respiratory syndrome coronavirus 2 (SARS-­CoV-­2) and is as- Human angiotensin-­converting enzyme 2 (ACE2) receptor serves as sociated with significant morbidity and mortality among vulnerable the binding domain of SARS-­CoV-­2 in human host cells, exploiting patients.1 This grim situation is mainly attributed to the poor under- its high affinity to this enzyme to inflict remarkable damage to key standing of the pathogenesis of SARS-­CoV-­2-­induced injury to vital target organs.5–­7 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original..