Earlier clinical improvement in mild-moderate acute COVID patients treated with pharmacological-grade Curcumin

Earlier clinical improvement in mild-moderate acute COVID patients treated with pharmacological-grade Curcumin | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 4 June 2025 V1 Latest version Share on Earlier clinical improvement in mild-moderate acute COVID patients treated with pharmacological-grade Curcumin Authors : Antonia Célia de Castro Alcântara , Daniele Leite Cunha de Queiroz , Ana Carolina M. Dinelly Pinto , Marcos Renato de Assis 0000-0002-6567-4570 , Hermano Alexandre Lima Rocha , and Francisco Rocha 0000-0003-4370-3294 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174904567.74543434/v1 239 views 142 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Heavy curcumin consumers apparently had a lower-than-expected COVID-19 death rate. Curcumin modulates angiotensin-converting enzyme expression, which may impair SARS-CoV-2 entry into host cells. Our data show that curcumin provides earlier recovery in acute COVID-19. Curcovid was an observational study conducted from Mar21-May22. Individuals > 18 years, with ≤2 days of symptoms, seen at Emergency Room or Telehealth system with positive SARS-Cov-2 PCR and mild/moderate disease were invited to immediately add a pharmaceutical-grade curcumin formulation (1g/d/10 days) alongside usual care. Primary outcomes were self-reported time to symptom relief and judgement of full recovery. Patients who used curcumin were compared to those who did not add the compound to their treatment regimen (Control). There were 73 and 58 patients in usual care and curcumin groups, respectively; mean age was 44.9 ± 13.9 years-old with 52 (39.7%) male; 3 days after study entry, fewer patients using curcumin had dyspnea (p=0.0164); systolic BP and serum creatinine were lower in curcumin group (p=0.0035 and 0.038, respectively). Time for symptom relief was 6.6±2.4 and 4.2±4 days in control and curcumin groups, respectively (p<0.0001); time for complete recovery was 12.4±5.3 and 7.8±6.7 days in control and curcumin groups, respectively (p<0.0001). No serious adverse events reported in both groups. Early administration of curcumin reduced time for complete recovery in acute COVID-19. Earlier clinical improvement in mild-moderate acute COVID patients treated with pharmacological-grade Curcumin Short title: Curcumin protection in acute COVID Antonia Célia de Castro Alcântara, MD, MSc 1 , Daniele Leite Cunha de Queiroz, MD 2 , Ana Carolina Matias Dinelly Pinto, PhD 1,6 , Marcos Renato de Assis MD, PhD 3 , Hermano Alexandre Lima Rocha, MD, PhD 4,5 , Francisco Airton Castro da Rocha, MD, PhD 1 * 1 Postgraduating program on Medical Sciences, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Brazil 2 Hospital Regional Unimed, Fortaleza-CE, Brazil 34 Professor of Rheumatology, Faculdade de Medicina de Assis (FEMA), SP, Brazil 4 Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 5 Department of Maternal and Child Health, Federal University of Ceará, Fortaleza, Brazil 6 Pasteur-Fiocruz Center on Immunology and Immunotherapy. Fiocruz. Fortaleza, Ceará, Brazil *FACR Corresponding author (ORCID 0000-0003-4370-3294) [email protected] ACCA (ORCID 0000-0003-2341-1251) DALCQ (ORCID 0009-0001-5632-1722) ACMDP (ORCID 0000-0002-2411-6708) MRA (ORCID 0000-0002-6567-4570) HALR (ORCID 0000-0001-9096-0969) Abstract Heavy curcumin consumers apparently had a lower-than-expected COVID-19 death rate. Curcumin modulates angiotensin-converting enzyme expression, which may impair SARS-CoV-2 entry into host cells. Our data show that curcumin provides earlier recovery in acute COVID-19. Curcovid was an observational study conducted from Mar21-May22. Individuals > 18 years, with ≤2 days of symptoms, seen at Emergency Room or Telehealth system with positive SARS-Cov-2 PCR and mild/moderate disease were invited to immediately add a pharmaceutical-grade curcumin formulation (1g/d/10 days) alongside usual care. Primary outcomes were self-reported time to symptom relief and judgement of full recovery. Patients who used curcumin were compared to those who did not add the compound to their treatment regimen (Control). There were 73 and 58 patients in usual care and curcumin groups, respectively; mean age was 44.9 ± 13.9 years-old with 52 (39.7%) male; 3 days after study entry, fewer patients using curcumin had dyspnea (p=0.0164); systolic BP and serum creatinine were lower in curcumin group (p=0.0035 and 0.038, respectively). Time for symptom relief was 6.6±2.4 and 4.2±4 days in control and curcumin groups, respectively (p<0.0001); time for complete recovery was 12.4±5.3 and 7.8±6.7 days in control and curcumin groups, respectively (p<0.0001). No serious adverse events reported in both groups. Early administration of curcumin reduced time for complete recovery in acute COVID-19. Keywords: COVID-19; SARS-Cov-2; coronavirus; turmeric; curcumin Introduction The COVID-19 pandemic has been the most serious health challenge of this century [1]. Although being currently milder, there are still concerns regarding the effectiveness of therapeutic measures aiming to avoid progression to a severe form of this viral disease. Socioeconomic issues may impact COVID-19 outcome due in part to delay in access to proper health care. In addition, antiviral agents that received a fast-track approval to treat COVID-19 patients come at high cost, usually being unaffordable either by official agencies or by direct purchase from individuals living in low-income countries [2]. Despite a lack of clear biomarkers to identify patients that will advance to severe COVID-19, it may seem undisputable that therapies targeting the reduction of viral replication could significantly decrease the chance for disease progression. Notwithstanding, symptom relief is also of help as an attempt to decrease the need for patients to seek emergency health care [3]. We have previously hypothesized that curcumin, the yellow pigment from Curcuma longa, could be a therapeutic option to alleviate symptoms and, possibly, decrease the chance of disease progression in COVID-19 patients. This hypothesis was based on observations that countries with high turmeric consumption have experienced a lower-than-expected death toll attributed to COVID-19, despite displaying public health challenges [4,5]. Also, data from in vivo experimental studies in rodents using edible curcumin showed modulation of the expression of the angiotensin-converting enzyme (ACE)2, which happens to be the gateway for SARS-Covid-2 virus entry into the human body [6-8]. Using computational modelling, the keto and enol forms of curcumin were shown to exhibit strong bond interactions with ACE2, which could block access to this protein, thus decreasing SARS-Covid-2 access to host cells [9]. These issues were recently revised showing that phytocompounds that are able to inhibit access to ACE2 may be therapeutic alternatives to COVID-19 [10]. In keeping with this assumption, decrease of the expression of ACE2 has been considered a key factor to the benefit experienced by corticosteroid use aiming to halt progression of Covid-2 [11,12]. Thus, the combination of observational epidemiological data and a potential pharmacological mechanism led us propose that curcumin could treat acute mild COVID-19 patients, possibly reducing the risk of disease progression [4]. There is a critical window of opportunity for treating COVID-19 aiming for the early stage of symptom onset where decrease in viral entry into host cells as well as blockade or reduction of viral replication would be critical [12]. Thus, strategies to decrease the burden of this disease, particularly if affordable, surely merit attention and have to be used promptly when the disease erupts, provided that a safe alternative is feasible. We performed a prospective open label, add-on, observational study to investigate whether the administration of a pharmaceutical grade curcumin formulation reduces symptom severity and shortens the time for complete clinical recovery in patients classified as having acute mild to moderate COVID-19 infection. These results are reported herein. Materials and Methods Study design and participants: The Curcovid study was an open label, observational, parallel-group study, conducted from March 15 2021 through May 5, 2022, at the Hospital Regional UNIMED (HRU) in Fortaleza, Ceará, Brazil. During the COVID-19 pandemic, the administration of the HRU implemented a protocol to help physicians make medical decisions regarding COVID-19, as described previously [13]. Inclusion criteria were individuals seen at the Emergency Room (ER) or using the implemented telehealth system by the HRU, aged older than 18 years, presenting within two days of the start of symptoms attributed to COVID-19, as follows: new onset cough, fever (axillary temperature ≥ 37.8°C), oropharyngeal pain, dyspnea, or anosmia, isolated or in combination, as judged by the attending physician. Exclusion criteria were physician clinical judgement of severe or critical COVID-19 and/or SpO₂ < 93% on room air. All patients included had a confirmed polymerase chain reaction test for SARS-Covid-2, obtained either at the ER or at the outpatient UNIMED laboratory facilities. Protocol: Data were collected directly from the medical records, gathering demographic, clinical, and laboratory results of all patients admitted to the outpatient care and emergency facilities structured at the HRU. Information on comorbidities included obesity (body mass index, BMI > 30), systemic arterial hypertension, diabetes, and chronic obstructive pulmonary disease. After initial evaluation, individuals judged to have mild disease and those with moderate disease not in the need or unwilling admission to the HRU were invited to add a commercially available pharmaceutical-grade curcumin formulation (Motore ® ) starting in the same day of the first visit, alongside any other therapeutic strategy, which will be considered as usual care at that time, be it non-pharmacological or pharmacological, consisting mostly of supportive care and antipyretics (paracetamol, dypirone, anti-inflammatory non-steroidal drugs), as prescribed by the attending physician. Decision to start antivirals, antibiotics, and/or corticosteroids, as well as need for hospital admission was done by the attending physicians either at the ER or through the telehealth service. Patients were informed of our hypothesis that curcumin could help improve COVID-19 symptoms and, possibly, accelerate disease recovery. Motore ® was required to be purchased by the patient and should be taken for 10 consecutive days, administering 2 capsules every 12 hours, as per the instructions of the manufacturer to treat chronic arthritis (Motore package insert). Patients had full access to the attending physicians either using the implemented telehealth service or by accessing the ER. Physicians at the HRU received training for the early management of COVID-19 patients, following a predetermined clinical protocol, which followed instructions of Brazilian public health authorities (Alcântara et al., 2022). Patients were contacted every 72 hours until day 12, using remote care access, to check for symptoms. Any hospital admission was considered a treatment failure leading to immediate stop of the curcumin formulation, if being used. Outcomes: The primary outcomes were self-reported time to initial relief of COVID’s symptoms and time to self-reported judgement of full recovery. Secondary outcomes included return to the ER, hospitalization, need for ventilator assistance, and death, as well as laboratory data available from medical records, with data right-censored as of May 5, 2022. Patients who used Motore ® (Curcumin group) were compared to those who did not add the compound to their treatment regimen (Control). All patients also completed a structured questionnaire via a phone call conducted by one of the co-authors (AACC) 28 days after study entry. Laboratory data were extracted from medical records. Safety was evaluated by recording the incidence of emerged adverse events after study entry up to 28 days after the first evaluation. Serious adverse events as judged by the attending physician and discontinuation of the curcumin preparation were specifically addressed in all patients that confirmed having taken at least one dosage of Motore ® . All data were stored using REDcap ™ software. Statistics: Primary and secondary outcomes were evaluated in patients that confirmed having taken at least one administration of Motore ® , answered the telehealth calls, and filled the questionnaire of clinical data evaluation, performed 3 days after the first visit and up to 28 days after study entry. Data are expressed as means (standard-deviation, SD) or medians (interquartile range, IQR) as appropriate, and comparisons were made using chi-square, Kruskal-Wallis, and rank-sum Wilcoxon tests. Survival curves were calculated for the time to symptom relief and self-evaluation of complete recovery. Difference between curcumin and placebo groups were compared using the Log Rank (Mantel-Cox) test. There was no imputation for missing data; comparison between groups was done using bivariate analysis. The level of significance was set at 0.05. Analysis of data were done using SAS 9.4 M7, SAS Inc. Ethical issues: This protocol received formal approval of the Comissão Nacional de Ética em Pesquisa, which is the National Council for analysis of Ethical issues on Human Studies in Brazil (Protocol number 30401920.6.0000.5049). Results Figure 1 illustrates a flow chart of patients included in the protocol. The total number of patients seen in the ER and Telehealth care of the HRU from April 2022 to April 2023 classified as presenting symptoms of an acute respiratory viral disease was 39759; among these, 24383 reporting ≥3 days of symptoms were excluded; 6196 among the remaining 15376 individuals with ≤2 days of symptoms did also have a positive RT-PCR test for COVID with 582 declaring having received a medical prescription of curcumin (Motore ® ), which was confirmed by checking the recorded clinical files; 357 out of these 582 patients could be contacted with 131 agreeing to be enrolled, meaning acceptance of answering the clinical questionnaire of the protocol, comprising 53 that took Motore ® for the prescribed 10 days, regarded as the active arm, and 78 that did not took Motore ® , considered as pertaining to the usual care (Control) arm of the protocol. Mean age was 44.9 ± 13.9 years-old with 52 (39.7) male. No significant differences were found regarding baseline data of both groups for demographics, comorbidities as well as use of medications other than Curcumin, as shown in table 1. There were 7 (9.5%) and 4 (6.8%) individuals older than 65 years in the Control and Curcumin groups. The most common comorbidity was obesity, being more frequent in the Curcumin group, though not reaching statistically significant difference to the Control group. In the first evaluation, 3 days after study entry, there were fewer patients in the Curcumin group with dyspnea (p=0.0164) while also having more nausea (p=0.0191) (Table 2). Three days after study entry, all clinical parameters were similar but the systolic arterial blood pressure was significantly lower (p=0.035) in the Curcumin group (Table 3). All laboratory work-out parameters were similar in the Control and Curcumin groups but serum creatinine was significantly lower (p=0.038) in the Curcumin group (Table 4). The primary outcomes were reached, as follows: median (IQR) time for initial symptom relief was 7 (4-8) and 3.5 (2-4) days in the Control and Curcumin groups, respectively (P<0.0001); median (IQR) time for complete clinical recovery was 12 (10-15) and 6 (5-8) days in the Control and Curcumin groups, respectively (P<0.0001) (Figure 2A and 2B). There were also fewer individuals in the Curcumin group that needed hospital admission, although this difference did not meet statistical significance (p=0.2089) (Table 5). All but one patient in the Control group needed assisted ventilation for 2 days, but he eventually progressed to full clinical recovery with discharge 31 days after hospital admission. No patient used specific antivirals, which were not available in Brazil at the time of the study. Table 5 illustrates the type of medications used to treat symptoms in the Control and Curcumin groups, which were similar. These medications included paracetamol, dypirone, nonsteroidal antiinflammatory drugs, and low-dose (< 10 mg) prednisone. The use of phytocompounds other than curcumin, grouped as other medications in table 5, was also similar in control and curcumin groups of patients. There were no serious adverse events in both groups. Discussion Our study is the first demonstration that a pharmaceutical-grade curcumin formulation reduces the time to symptom relief and complete recovery of acute mild-moderate COVID-19. Collecting these data was not an easy task as the inclusion criteria had to be very stringent, given the non-randomized, open label, observational characteristic of the protocol. That was the reason to include only 58 patients in the Curcumin group although 582 had a register of a medical prescription of curcumin to treat acute COVID. In addition to target the hypothetically very narrow window of opportunity to halt disease progression with curcumin, we also tried to include patients with the most reliable data to allow comparison. It is noteworthy that the average time for symptom relief was reduced by over 2 days, being significantly lower in the curcumin group. Moreover, patients that received curcumin reported to be fully recovered nearly 5 days earlier than patients in usual care. A previous study suggested that reducing the median time for resolution of symptoms in one day would be a minimum to be regarded as clinically meaningful [14]. In the present study, patients that took Curcumin had a 6 days median time for resolution, as compared to 12 days in the Control group, thus indicating clinical relevance. Although being an open-label study, we believe this is the most relevant positive result with an affordable, safe medication, promoting earlier recovery of COVID-19 patients with mild-moderate disease in an outpatient setting. Our assumption is that curcumin reduces the viral burden in the very early days after infection, thus shortening the time for complete recovery. Although these were mostly mild patients, the results are sounding given the well-known excellent safety profile of curcumin [15]. Indeed, there were no serious adverse events in the active arm of this protocol with only a few more patients in the curcumin group complaining of nausea. Our focus targeting very early mild patients was based on an hypothesis-driven protocol [4] as well as concerns aiming not to delay initiation of medications, e.g. steroids and/or invasive procedures judged to be needed in more severe patients at later stages [16]. We also observed that fewer patients in the curcumin group needed to revisit the ER, though this difference did not reach statistical significance. Reducing disease severity in patients with severe life-threatening situations is obviously a major goal in the approach to COVID-19. However, providing prompt relief in patients with milder disease, in addition to the individual benefit, may prevent disease progression. In this regard, strategies with affordable safe compounds such as this curcumin formulation merit consideration. Although COVID-19 can be currently considered a milder disease, access to monoclonal antibodies and antivirals, which may provide help in the early stages of this disease, is not affordable for patients living in socially disadvantaged regions. Similarly, budesonide, which was shown to provide faster recovery with an impressive low number-needed-to-treat (NNT) result, is also hard to be provided in disadvantaged regions [12]. Dexamethasone, despite being a cheap alternative, easy-to-find compound, can only be used with proper medical advice in COVID-19, which can be a significant hurdle in developing countries due to difficult access to specialized care [17]. Recently, strategies to manage individuals with mild to moderate COVID-19 in the outpatient setting considered that the antivirals molnipuravir, combined nirmatrelvir-ritonavir or remdesivir had to be started within 5 to 7 days of symptom onset. Interestingly, evidence was based on data showing that molnupiravir probably does not modify time to recovery or hospital admissions, whereas combined nirmatrelvir-ritonavir showed moderate certainty of reducing all-cause mortality and hospital admissions [2,18,19]. Similarly, data on remdesivir were considered as of low certainty of a probable improvement in recovery and reduction of hospital admissions. Taken as a whole, recently updated recommendations indicate that further data and options are needed in order to halt COVID-19 progression [16]. We initially attempted to conduct a placebo-controlled randomized study. However, a large number of patients were reluctant to accept being in the placebo arm, not to mention those questioning the scientific rationale of the study, though not questioning the probable safety of curcumin. This led us propose that patients would purchase the curcumin prescription-grade formulation. The choice for using Motore ® was due to the fact that this is the only pharmaceutical-grade curcumin preparation available at that time in Brazil. This product had undergone complete pharmaceutical studies, with data showing clinically relevant serum curcuminoid levels achieved shortly following oral ingestion in healthy volunteers [20]. Motore ® also has published safety data and is marketed as a medication in Brazil, rather than as a dietary supplement [21,22]. The use of pharmaceutical grade preparations has been regarded crucial when using nutraceuticals and phytocompounds to treat osteoarthritis [23]. Thus, despite the inconvenience of taking two capsules every 12 hours, for 10 days, we chose this formulation. Adherence is always an issue, particularly when conducting studies with oral compounds and, in this case, purchased by the patient. Our strategy to make phone calls every 72 hours via the implemented telehealth system, with trained nurses, aimed to check for symptoms as well as adherence to the prescribed treatment. Interestingly, patients in the curcumin group had more nausea, likely because they were taking the medication. Moreover, systemic arterial blood pressure and serum creatinine, despite being in the normal range in both groups, were significantly lower in the curcumin group, as compared to patients in usual care. We mentioned above that edible curcumin was shown to decrease the expression of ACE2, which could be a pathway for reducing SARS-Covid-2 entry into host cells [4]. Although hard to prove, it is conceivable that patients taking curcumin could have a decrease in blood pressure associated with reduced activity of the angiotensin-converting enzyme system, as well as optimization of the glomerular filtration rate [6-8]. Let us not forget that patients had to purchase the compound for themselves. Given this scenario, after feeling symptom relief and being stimulated to keep using the medication, patients would likely maintain the medication as prescribed. An important aspect of this protocol was the timing for initiating the medication. Patients were required to have not more than 2 days of symptoms. This was basically due to our assumption that curcumin, as virtually any compound to date, can beyond doubt be less effective or simply ineffective once the disease progresses. If the objective is to halt viral entry, or at least the viral burden, the window of opportunity is critically narrow. The long-term safety data on curcumin and the possibility that it can also display specific antiviral activity [24] encouraged us to choose a very short period of symptoms, which obviously posed a significant hurdle for the screening of patients. Although speculative, we truly believe this strategy was crucial to prove the success of the intervention. Our study is not without limitations, primarily due to the non-randomized, open-label, observational characteristic of the protocol. Be as it may, we managed to collect data from a reasonable number of patients, which were carefully followed. The fact that we did not provide the curcumin can also be an issue to limit patient participation. We should also consider that having a placebo arm at the time proved impractical. However, no specific treatment existed or still can be said to exist to be considered a gold-standard in mild-moderate acute COVID-19, particularly in an outpatient setting. The relatively low number of individuals does also preclude analysis of subgroups. We also did not check for long-term follow-up, which could be of relevance given the emerging long COVID features that have been reported [25]. Our findings show that a pharmaceutical-grade curcumin formulation decreased the time for symptom relief and complete recovery in patients with mild-moderate acute COVID-19. Although our data should be confirmed in larger randomized trials, the safety profile of curcumin encourages using this compound at the very early onset of symptoms that can be attributed to a COVID-19 infection. Acknowledgement and funding : This work was partially supported by for Rocha FAC by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ grants 313860/2021-1 and 403767/2021-0). Author Contributions statement: ACCA conceived, conducted, processed the data, and wrote the manuscript; DLCQ conducted and processed the data of the protocol; HALR statistical analysis; MRA and ACMDP analysed the data; FACR conceived, conducted, processed the data, and wrote the manuscript; all authors read, revised, and approved the final version of the manuscript. References 1. World Health Organization. WHO Coronavirus (COVID-19) Dashboard. https:// covid 19. who. int/ table 2021. 2. Schilling WHK, et al. Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial. Lancet Infect Dis . 2024;24(1):36-45. Erratum in: Lancet Infect Dis . 23; 12:e511. (2023) 3. Paules CI, Fauci AS. COVID-19: the therapeutic landscape. Med (N Y). 2: 493–97. (2021). 4. Rocha FAC, de Assis MR. Curcumin as a potential treatment for COVID-19. 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Real-world use of remdesivir for the treatment of patients admitted to Italian hospitals with COVID-19: the nationwide retrospective FADOI-RECOVER study. BMC Infect Dis . 23 ,454 (2023). 20. Cuomo J et al. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J Nat Prod. 74(4):664-9 (2011). 21. Belcaro G et al. Efficacy and safety of Meriva ®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Altern Med Rev. 15(4): 337-44 (2010). 22. Musso G, et al. Effect of phospholipid curcumin Meriva on liver histology and kidney disease in nonalcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial. Hepatology. 81(2): 560-575 (2025) 23. Bruyère O, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 49(3): 337-50 (2019). 24. Kahkhaie KR, et al. Curcumin: a modulator of inflammatory signaling pathways in the immune system. Inflammopharmacology. 27:885–900 (2019). 25. Al-Aly Z, et al. Long COVID science, research and policy. Nature medicine . 30(8): 2148–64 (2024). Tables Table 1 . Baseline demographics and clinical characteristics of COVID patients treated with Curcumin as adjunct therapy Control (73) Curcumin (58) Total (131) P-value Age (years) 0.7529 Mean (SD) 45.3 44.7 (13.6) 44.9 (13.9) Gender 0.2983 Female 47(64.38) 32 (54.5%) 79 (60.3%) Male 26 (35.61) 26 (45.5%) 52 (39.7%) Comorbidities 0.1345 COPD 1 (1.26 %) 1 (1.7%) 2 (1.52%) Diabetes 4 (5.06%) 0 (0.0%) 4 (3.05%) SAH 9 (11.3 %) 6 (10.3%) 15 (11.4%) Obesity (BMI>30) 9 (11.3 %) 15 (25.8%) 24 (18.3%) Medications 0.3974 NSAID 6 (8.2%) 1 (1.7%) 7 (5.3%) Antipyretic 5(6.8%) 5 (8.6%) 10 (7.6%) Steroids 13 (9.92%) 7 (12.0%) 20 (15.2%) Other 18 (13.7%) 15 (25.8%) 33 (25.1%) Data represent N(%) ; COPD, chronic obstructive pulmonary disease ; NSAID, nonsteroidal antiinflammatory drug ; SAH, systemic arterial hypertension. Control and Curcumin groups compared using bivariate analysis. The level of significance was set at 0.05 Table 2 – Clinical symptoms of COVID-19 patients treated with Curcumin as adjunct therapy three days after study entry Cough 0.7321 Sim 48 (75.4%) 37 (63.8%) Não 25 (34.2%) 21 (36.2%) Loss smell/taste 0.9189 Mild 19 (26.0%) 15 (25.9%) Moderate 2 (2.7%) 1 (1.7%) Absence 52 (71.2%) 42 (72.4%) Sore throat 0.3043 Mild 30 (41.0%) 32 (55.2%) Moderate 2 (2.7%) 1 (1.7%) Absence 41 (56.1%) 25 (43.1%) Dyspnea 0.0164 Yes 15 (20.5%) 3 (5.2%) No 59 (79.4%) 55 (94.8%) Nausea 0.0191 Yes 2 (2.7%) 8 (13.8%) No 71 (97.2%) 50 (86.2%) Diarrhea 0.6496 Mild 8 (10.9%) 8 (13.8%) Moderate 1 (1.3%) 2 (3.4%) Absence 64 (87.6%) 48 (82.8%) Dizziness 0.2143 Yes 2 (2.7%) 2 (5.2%) No 72 (98.6%) 56 (96.5%) Data represent N(%). Control and Curcumin groups compared using bivariate analysis. The level of significance was set at 0.05 Table 3 - Clinical data of COVID patients treated with Curcumin as adjunct therapy three days after study entry Control (73) Curcumin (58) P value Axillary temperature (ºC) Mean (SD) 37.4 (0.79) 37.3 (0.80) 0.1403 Median (IQR) 37.8 (36.9 - 37.9) 37.0 (37.0 - 38.0) Heart rate (bpm) Mean (SD) 91 (13.23) 85 (13.56) 0.2524 Median (IQR) 93 (79 - 104) 83 (80 - 100) Respiratory rate (rpm) Mean (SD) 23 ( 4.8 ) 21 (3.9) 0.7806 Median (IQR) 22 (27 - 29) 22 (18 - 22) SAP (mmHg) Mean (SD) 130.28 (13.6) 122.4 (10.6) 0.0350 Median (IQR) 130 (119 - 152) 120 (120 - 130) DAP (mmHg) Mean (SD) 81.9 (9.9) 78.2 (9.3) 0.4708 Median (IQR) 80 (73 - 90.5) 80 (75 - 80) SAP, systolic arterial pressure; DAP, diastolic arterial pressure. Control and Curcumin groups compared using bivariate analysis. The level of significance was set at 0.05. Table 4 – Laboratory work-out of patients with acute COVID-19 treated with Curcumin as adjunct therapy three days after study entry Control (73) Curcumin (58) P value Hemoglobin (g/dL) 13.8 (1.6) 13.7 (1.4) 0.3070 Leukocytes (/mm 3 ) 6788 (10344) 6525.6 (6130) 0.1505 Platelets (/mm 3 ) 235814 (66143) 106292 (158057) 0.6474 Creatinin (mg/dL) 0.9 (0.3) 0.7 (0.19) 0.0380 C reactive protein (mg/dL) 14.98 (26.2) 6.87 (5.8) 0.9829 D-dimer (ng/mL) 1121 (1017.7) 946.7 (1996.8) 0.3128 Ferritina 791.86 (1029.9) 717.0 (1159.8) 0.8487 Fibrinogênio 446.28 (215.6) 382.5 (122.7) 0.6396 Glucose (mg/dL) 96.84 (13.48) 101.9 (27.5) 0.5836 Sodium (mEq/L) 138.3 (3.6) 137.7 (1.6) 1.0000 Potassium (mEq/L) 4.1 (0.2) 4.0 (0.4) 0.7456 ALT (U/L) 40 (35) 62 (84) 0.9179 Partial thromboplastin time activated 23.4 (8.2) 19.7 (5.8) 0.1164 Prothrombin time 15.05 (5.8) 14.1 (4.8) 0.4970 Data represent plasma levels collected from patients with COVID-19. ALT, alanine aminotransferase. Control and Curcumin groups compared using bivariate analysis. The level of significance was set at 0.05. Table 5 – Patient reported outcomes of COVID-19 patients treated with curcumin as adjunct therapy Control (73) Curcumin (58) P value Time (d) for symptom relief Mean (SD) 6.64 (2.46) 4.2 (4.01) <0.0001 Median (IQR) 7 (4 - 8 ) 3.5 (2.0, 4.0) Time (d) for clinical recovery Mean (SD) 12.4 ( 5.32) 7.8 (6.79) 0.0001 Median (IQR) 12.0 (10, 15.0) 6.0 (5.0, 8.0) Visit to the ER after first evaluation Yes 7 (12.1) 7 (9.5). 0.3036 No 66 (90.4) 51 (87.9) Need for hospital admission after first evaluation Yes 6 (8.2) 3 (5.2) 0.2089 No 67 (91.7) 55 (94.8) Data represent n (%) or as indicated. ER, emergency room. Full recovery was considered to occur when patients considered themselves completely asymptomatic, both in those of the curcumin group that received at least one dose of the compound and in the placebo group. Control and Curcumin groups compared using bivariate analysis. The level of significance was set at 0.05. Legend to the figure Figure 1 – Flow of patients in the CURCOVID trial of curcumin for treatment of mild-moderate acute SARS-CoV-2 Infection Figure 2. Patients in the curcumin group received treatment with Motore (2 capsules every 12 hours for 10 consecutive days), control group maintained standard treatment. The cumulative survival of one less was evaluated the time for relief of symptoms (A) and the time for clinical recovery (B) in days. Data are expressed as medians (interquartile range, IQR). The level of significance was set at 0.05. Information & Authors Information Version history V1 Version 1 04 June 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords antiviral agents coronavirus pathogenesis respiratory tract sars coronavirus virus classification Authors Affiliations Antonia Célia de Castro Alcântara Universidade Federal do Ceara Faculdade de Medicina View all articles by this author Daniele Leite Cunha de Queiroz Universidade Federal do Ceara Faculdade de Medicina View all articles by this author Ana Carolina M. Dinelly Pinto Universidade Federal do Ceara Faculdade de Medicina View all articles by this author Marcos Renato de Assis 0000-0002-6567-4570 Fundacao Educacional do Municipio de Assis View all articles by this author Hermano Alexandre Lima Rocha Universidade Federal do Ceara Faculdade de Medicina View all articles by this author Francisco Rocha 0000-0003-4370-3294 [email protected] Universidade Federal do Ceara Faculdade de Medicina View all articles by this author Metrics & Citations Metrics Article Usage 239 views 142 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Antonia Célia de Castro Alcântara, Daniele Leite Cunha de Queiroz, Ana Carolina M. Dinelly Pinto, et al. Earlier clinical improvement in mild-moderate acute COVID patients treated with pharmacological-grade Curcumin. Authorea . 04 June 2025. 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