Preliminary evaluation of the efficacy and safety of a traditional poly-herbal preparation “Desadun Kalka” in reducing symptoms and inflammatory mediators in patients with acute COVID-19

Preliminary evaluation of the efficacy and safety of a traditional poly-herbal preparation “Desadun Kalka” in reducing symptoms and inflammatory mediators in patients with acute COVID-19 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Preliminary evaluation of the efficacy and safety of a traditional poly-herbal preparation “Desadun Kalka” in reducing symptoms and inflammatory mediators in patients with acute COVID-19 Rameeladevi Thatparan, Sudharma Umayangani, Gunapala Amarasinghe, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5966181/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction : During the COVID-19 pandemic, many traditional herbal medicines were used to treat patients with COVID-19. We sought to determine the efficacy and safety of a traditional polyherbal preparation-Desadun Kalka (DK) in reducing symptoms and inflammatory mediators in patients with COVID-19 in Sri Lanka. Methods : We conducted a phase 2, randomized, open labelled clinical trial, in hospitalized adult patients with a confirmed SARS- COV-2 infection, enrolled within the ≤ 4 days since onset of symptoms. Those in the treatment arm (n=76) were given 1250mg of DK three times a day orally, starting from the day of recruitment, up to 4 to 5 days (median 4 days, IQR 4 to 5 days) along with the standard treatment, while those in the control arm (n=76) were given standard treatment. Results: Patients in the DK arm and control arm had similar baseline characteristics except for those in the DK arm having significantly lower (p=0.007) Ct values for SARS-CoV-2 specific RT-qPCR than those in the control arm. DK was well tolerated, and no adverse events were reported. Patients in the DK arm were significantly less likely to have symptoms of a cold (p=0.006) and cough (p=0.006) on day 8 since onset of illness compared to the control group and had a significantly shorter duration of a cough (p=0.006). The CRP levels (p=0.001) and the serum IL-6 levels (p<0.0001) were significantly lower on day 8 of the illness in those who were in the DK arm compared to those in the control arm, while there were no differences in other clinical features, or haematological or biochemical parameters in the DK vs control group. Conclusion : DK appears to have some effect in reducing symptoms and inflammatory mediators in patients with COVID-19 and it would be important to further evaluate the efficacy and mechanisms of action. Trial registration: the trial was registered at the Sri Lanka Clinical trial registry on the 1st of March 2021, International Clinical Trial Registration Platform (SLCTR/2021/005: https://slctr.lk/trials/slctr-2021-005 ) COVID-19 polyherbal preparation inflammatory mediators CRP IL-6 Desadun Kalka Figures Figure 1 Background During the COVID-19 pandemic many treatments such as antivirals, monoclonal antibodies and immunomodulatory treatments were developed within a very short time span with hundreds of clinical trials being conducted globally [1]. Clinical trials for COVID-19, included antiviral drugs such as hydroxychloroquine, lopinavir-ritonavir, molnupiravir and the nirmatrelvir plus ritonavir combination and immunomodulatory drugs such as dexamethasone, IL-6 antagonists and Janus kinase inhibitors [1–4]. Many trials conclusively showed that while hydroxychloroquine and lopinavir-ritonavir did not seem to reduce disease severity or hospitalization [2, 5], molnupiravir reduced hospitalization and death in unvaccinated adults [3] and the nirmatrelvir plus ritonavir combination reduced progression to severe disease [4]. However, hydroxychloroquine was shown to offer moderate benefit in preventing COVID-19 when taken as a prophylactic treatment [6]. Immunomodulators such as dexamethasone were shown to significantly reduce the 28-day mortality in those with moderate to severe COVID-19 requiring oxygen [7], while IL-6 antagonists were shown to decrease mortality for critically ill patients requiring oxygen and receiving dexamethasone [1]. Apart from development of new therapeutics and repurposing existing therapies for COVID-19, several countries reported the use of traditional medicines [8, 9]. By the end of 2020 over 3600 traditional drugs were undergoing clinical trials for COVID-19 alone in India [9]. Many of these drugs that underwent clinical trials in India and China, have been used for centuries, and have shown to have antiviral or immunomodulatory properties [9, 10]. Possibly as traditional medicine in ingrained in many Asian cultures, a significant proportion of individuals in Asia were found to use traditional medicine in the prevention and treatment of COVID-19 [11, 12]. Traditional medicine has been practiced for centuries in Sri Lanka, and many types of traditional medicine was used for treatment of COVID-19, during the pandemic [13]. However, many of these treatment methods were not formally assessed for their effectiveness in reducing COVID-19 clinical disease severity and complications. One of the poly-herbal preparations that have been used as an immunomodulator is Desadun Kalka (DK), which has been used for the prevention of respiratory infections, skin rashes and as a curative treatment for fever, inflammation, respiratory diseases and various skin diseases [14, 15]. DK was shown to reduce yeast induced elevation of body temperature in Wistar rats [16] and was also have antimicrobial effects in bacterial cultures of Staphylococcus aureus , Pseudomonas aeruginosa , and Listeria monoytogenes [17]. Although DK has been used for centuries, even in infants, the efficacy of this polyherbal preparation has not been assessed. As it is estimated that 80% of the global population use traditional medicine, with 170 of the 194 member states of the WHO regularly using them [18], it was important to evaluate the efficacy of these medicine in the treatment of COVID-19. Therefore, to evaluate the possible efficacy and safety of DK in treatment of COVID-19, we carried out a phase 2, randomized, open labelled clinical trial in Sri Lanka, to determine the efficacy of DK in reducing symptoms and inflammatory mediators in patients with COVID-19. Methodology Study Design and Oversight This study was a randomized, open labeled clinical trial, consisting of two arms, where the test group were given DK along with standard treatment and the control group was given standard management recommended by the Ministry of Health Sri Lanka ( please see supplementary data for trial protocol). The study was carried out at the National Institute of Infectious Disease (NIID), Angoda, Sri Lanka, during April 2021 to December 2021. The ethical approval for this clinical trial was obtained from the Ethics Review Committee of University of Sri Jayewardenepura (Covid 15/20) and the trial was registered at the Sri Lanka Clinical trial registry on the 1st of March 2021, International Clinical Trial Registration Platform (SLCTR/2021/005: https://slctr.lk/trials/slctr-2021-005 ). All individuals gave informed written consent and all methods involving human patients were performed in accordance with the relevant guidelines and regulations. Patient recruitment and follow-up Patients who were confirmed to have COVID-19 following a positive RT-qPCR result for the presence of SARS-CoV-2 virus, and a duration of illness of ≤ 4 days were included following informed written consent. The day of onset of illness was defined as the day of onset of symptoms. The pregnant and breast-feeding mothers, patients who were unable to take the drug orally, those with chronic liver disease or kidney disease and those who had severe and moderate COVID-19 illness according to the WHO COVID-19 disease severity classification [19] were excluded from the study at the initial assessment. The medical personnel managing the patients in the wards recorded the data on the patients’ clinical records, assessed the patients for clinical disease severity, and decided on the management of the patients. The investigators who handed out the treatment did not have any role in recording the clinical data on the patients’ records or in the management of the patients. The investigators involved in dispensing the drug and collecting the data, obtained all data from the patient’s clinical records. All clinical features were recorded including any adverse effects that could be related to the drug. The haematological and biochemical parameters were recorded from the laboratory results entered in the clinical records. The data was obtained on the day of recruitment and on day 10 of illness (and not day 10 since recruitment). Although PCRs to determine the viral loads on day of recruitment and again on day 10 since recruitment were to be done, this could not be carried out, as hospital and the laboratories involved in this study was overburdened during the massive COVID 19 outbreak due to delta variant that was experienced in Sri Lanka from July to October 2021. Randomization Patients who gave consent for the study were randomized to receive DK or be in the control arm in 1:1 ratio, which was decided using a computerized random number generator of sequential patients who were admitted to the COVID-19 wards in the hospital. Those in the DK arm were given 1250mg of DK three times a day orally, starting from the day of recruitment up to 4 to 5 days (median 4 days, IQR 4 to 5 days) along with the standard treatment. Although the study was planned to give the patients, DK for 10 days, as the patients were discharged from hospital much earlier due to high number of hospital admissions, they were only given the drug for 4 to 5 days, since the date of recruitment (Fig. 1 and Table 1 ). The control group was given standard management as per the Ministry of Health COVID-19 management guidelines. Table 1: Baseline characteristics of the patients at the time of recruitment in the treatment arm and the control arm DK arm N = 76 Control arm N= 76 P value Age (median, ±SD) (47.5, SD±14.65) (46, SD±18.44) 0.16 Sex Male (%) 44 (57.89%) 38 (50%) Female (%) 32 (42.1%) 38 (50%) Duration of illness on day of recruitment Mean (±SD) days Median (IQR) days 3.4 (0.74) 4 (3 to 4) 3.4 (0.75) 4 (3 to 4) 0.92 CT value (Viral load) Median (IQR) 15 (14 to 18) 17 (15 to 20) 0.007 Comorbidities: N (%) Diabetes Hypertension Dyslipidaemia Ischaemic heart disease Asthma 25 11 6 1 2 23 11 3 1 2 Laboratory parameters - on Admission WBC (Median, IQR) ×10 9 / L 7.01 (5.50 to 8.29) 6.205 (4.76 to 8.27) 0.06 Neutrophil (Median, IQR) ×10 9 /L 3.73 (2.85 to 5.26) 3.720 (2.525 to 4.93) 0.35 Eosinophil (Median, IQR) × 10 9 / L 0.09 (0.019 to 0.22) 0.1 (0.04 to 0.24) 0.31 Monocyte (Median,IQR) × 10 9 / L 0.59 (0.46 to -0.73) 0.55(0.45 to 0.71) 0.34 Lymphocytes (Median, IQR) ×10 9 /L 2.045 (1.58 to 2.788) 1.79 (1.278 to 2.628) 0.08 AST (Median, IQR) U/L 34 (24.15 to 47) 32.88 (25 to 46.68) 0.89 ALT (Median, IQR) U/L 37 (24.25 to 63.25) 35.5 (26 to 56) 0.70 CRP (Median, IQR) mg/dl 13.15(6.3 to 24.15) 17.35(4.575 to 26.63) 0.73 The trial drug Desadun Kalka (DK) is a traditional polyherbal preparation that has been used for centuries in ayurvedic medicine. This Kalka was prepared according to the procedure mentioned in Ayurveda Pharmacopoeia DK is composed of Dolichos biflorus Linn (Horse gram), Acorus calamus Linn (Calamus), Glycyrrhiza glabra Linn (Licorice), Pterocarpus santalinus Linn (Red Sandalwood), Santalum album Linn (Suduhandun), and Rock salt. All these ingredients were identified and authenticated by the botany division and quality assurance laboratory of Bandaranaike Memorial Ayurvedic Research Institute (BMARI). The physical impurities of the herbal ingredients were removed washed and dried in the shade and disintegrated individually into fine powder. These individual powders were sieved separately through 0.12mm mesh. The fine powder of the above herbal ingredients was taken in equal amounts and mixed together. The rock salt and was dissolved in lime juice. The salt and lime juice was mixed well with fine powders of all five herbal ingredients and kept for 24 hours in the clay pot at the room temperature. Finally, the mixture was grounded together into the form of paste to form the drug. DK was prepared with an equal consistency in the BMARI pharmacy and stored in prepacked envelopes in a designated cupboard, at room temperature. The final drug preparation was dispensed as a 1250mg single dose. Trial end points The primary objective in this study was to evaluate the efficacy of ‘Desadun Kalka (DK)’ in reducing the severity and duration of symptoms in COVID-19 infection. The secondary objectives were to study the safety of DK in patients with COVID-19, by assessing the haematological and biochemical parameters of the patients. In addition, the other secondary objectives were to assess the effects of DK on the duration of clinical symptoms using the WHO ordinal outcome scale and to determine if DK reduced viral loads. The day of onset of illness was defined as the day of onset of symptoms. Assays to determine serum IL-6 levels Serum samples were diluted in the sample diluent (SD13) and loaded into cartridges with relevant controls for high and low controls. Multiplex and single plex ELLA cartridges were run for IL-6, (Protein Simple, USA, SPCKB-PS-000276) with their high and low control concentrates IL-10 IL-6 (Cat:895003) in ELLA analyzer (ELLA 19050375 version 3.4.0.52, Protein Simple, USA) Measurements were taken in triplicates in separate glass nanoreactors (GNRs) for each cytokine of each sample in pg/ml. Statistical analysis The sample size was calculated to determine the efficacy of DK in reducing the duration taken for relief in symptoms (fever, cough, sore throat and anosmia) between the treatment group and the control group. It was assumed that the variance (duration of symptoms) was 6.5 days with a dropout rate was 5%. According to detect a difference in the two groups with a significance level of 5% and a power of 1 - β, it was calculated to be 76 in each arm (total 152 patients). The primary end point of the trial was the reduction in number of individuals who developed severe disease a reduction in the symptoms and duration of symptoms (cough, sore throat, fever, anosmia) associated with COVID-19. The secondary endpoint that was used in the analysis was the changes in biochemical and haematological parameters (to assess safety) and a reduction in inflammatory mediators (CRP and IL-6 levels). Statistical analysis was performed using Graphpad PRISM version 8.3. The differences in duration of different symptoms, haematological, biochemical parameters and inflammatory markers in samples collected at the time of recruitment (baseline) and at 8 day from the onset of illness were done using the two tailed Mann-Whitney U-test. The degree of association between inflammatory markers and biochemical and haematological parameters was analyzed using Spearman correlation coefficient test. Results The baseline characteristics of patients who were assigned to receive DK and who were randomized to be in the control arm are shown in Table 1 . There was no difference in the baseline characteristics except for the Ct values in the SARS-CoV-2 specific RT-qPCR, where those who were assigned to the DK arm were found to have significantly lower (p = 0.007) Ct values (higher viral loads) than those who were in the control arm. 76 patients in the DK arm completed 4 to 5 days (median 4 days, IQR 4 to 5 days) of DK and standard treatment, while 76 patients in the control arm received standard treatment for the same duration. According to admission policy for COVID-19 in Sri Lanka, anyone with COVID-19 who wished to get admitted to hospital, even if they had mild illness could do so, and therefore, all those who were recruited to our study had mild illness. The baseline characteristics at the time of recruitment to the study were also assessed (Table 2 ) and there were no significant differences in the baseline clinical features at the time or enrollment. Table 2 Symptoms at the time of recruitment in patients who were in the treatment arm and control arm Clinical symptoms DK arm N = 76 Control arm N = 76 Relative risk (95% CI) P value Fever 43 (56.5%) 43 (56.5%) 0.75 to 1.33 > 0.99 Cough 63 (82.9%) 54 (71.05%) 0.979 to 1.41 0.12 Cold 28 (36.84%) 25 (32.89%) 0.726 to 1.73 0.73 Headache 15 (19.73%) 20 (26.31%) 0.417 to 1.338 0.44 DIB 23 (30.26%) 23 (30.26%) 0.618 to 1.617 > 0.99 Sore throat 13 (17.1%) 12 (15.7%) 0.536 to 2.19 > 0.99 Diarrhoea 1 (1.3%) 2(2.6%) 0.06 to 3.74 > 0.99 Myalgia 17 (22.36%) 19 (25%) 0.507 to 1.574 0.85 Vomiting 1 (1.3%) 0 (0) 0.26 to infinity > 0.99 Anosmia 6 (7.8%) 3 (3.9%) 0.57 to 7.11 0.49 Loss of appetite 5 (6.5%) 7 (9.2%) 0.2482 to 2.042 0.765 Adverse events All adverse events were recorded and reported as classified by using the Common Terminology Criteria for adverse events, which has been used in reporting of adverse events in previous drug trials for COVID-19 [20]. None of the patients developed pneumonia or multi-organ failure (this was an exclusion criteria) and none of the patients succumbed to their illness (Table 3 ). There was no difference in the adverse events reported in the DK arm compared to the control arm. Table 3 Adverse reactions observed in patients in the treatment arm and control arm since day 10 since onset of illness Side effect DK arm N = 76 Control arm N = 76 Relative risk P value( 0.99 Vomiting 1 (0.75%) 0 (0) 0.26 to infinity > 0.99 Headache 0 2 (2.63%) 0 to 0.19 0.49 Hepatitis (ALT > 250/L) 0 0 0 > 0.99 AST (Median, IQR) (< 40 U/L) 34, (24.3–47) 32.88 (25 to 46.8) 0.92 to 1.35 0.34 ALT (Median, IQR) (< 55U/L) 37, (24.5–66.5) 35.5 (26- to 56) 0.40 to 1.4 0.54 Low white cell counts (< 4×10 9 /L) 0 2 (2.63%) 0 to 1.88 0.49 Low platelet counts ( 0.99 Overall efficacy of DK To assess the efficacy of DK compared to standard treatment alone the differences in clinical and laboratory features of those on DK and the control arm were compared. None of the patients in the DK arm or control arm had fever by day 8 since onset of illness and there was no difference in the duration of fever in both arms (Table 4 ). Interestingly, those on the DK arm were significantly less likely to have symptoms of a cold (p = 0.006) and a cough (p = 0.006) on day 8 since onset of illness compared to the control group. Those who were on DK also had a significantly shorter duration of a cough (p = 0.006), compared to the control group (Table 4 ). However, there was no difference in the duration of a sore throat, myalgia, anosmia and loss of appetite in both groups. None of the patients in the DK arm and 2 patients in the control arm developed difficulty in breathing, which was not significant. Table 4 Clinical symptoms on day 8, since onset of illness in those in the treatment arm and control arm Clinical symptoms DK arm N = 76 Control arm N = 76 Relative risk (95% CI) P value (< 0.05) Presence of Fever: N (%) 0 0 0 Duration of fever (Median, IQR) 4 (0 to 5.75) 4 (0 to 6) 0.31 Presence of symptoms of cold: N (%) 0 8 (6.08%) 0.0 to 0.45 0.006 Duration of cold (Median, IQR) 0 (0 to 5.75) 0 (0 to 6) 0.69 Presence of cough: N (%) 0 12 (9.12%) 0 to 0.03 0.0003 Duration of cough (Median, IQR) 6 (4.25 to 7) 7 (0 to 9) 0.006 Difficulty in breathing –N (%) 0 2 (1.52%) 0 to 1.89 0.49 Duration of difficulty in breathing (Median, IQR) 0 (0 to 4) 0 (0 to 6) 0.29 Presence of Sore throat – N (%) 0 0 0 < 0.99 Duration of sore throat (Median, IQR) 0, 0 0, 0 0.52 Presence of myalgia – N (%) 0 4 (3.04%) 0.93 0.12 Duration of myalgia (Median, IQR) 0, 0 to 3.75 0, 0 0.28 Presence of anosmia – N (%) 0 2 (1.52%) 0.26 to infinity > 0.99 Duration of anosmia (Median, IQR) 0, 0 0, 0 0.49 Loss of Appetite – N (%) 0 2 (1.52%) 0 to 1.89 0.49 Duration of LOA (Median, IQR) 0, 0 0, 0 0.25 The CRP levels (p = 0.001) and the serum IL-6 levels (p < 0.0001) were significantly lower on day 8 of the illness in those who were in the DK arm compared to those in the control arm (Table 5 ). There was no difference in the total white cell counts, neutrophil, lymphocyte, monocyte and eosinophil count in those in the DK arm compared to the control arm. Serum fibrinogen levels, procalcitonin, D-dimer levels, ferratin and lactic dehydrogenase levels and chest imaging was only done on selected patients who develop severe disease and are admitted to the intensive care units or high dependency units and were not carried out in any of these patients included in the study. Table 5 Haematological and inflammatory markers in the treatment arm and the control arm on day 8 since onset of illness DK arm N = 76 Control arm N = 76 P value CRP (Median, IQR) mg/dl 4.25 (3.1 to 7.0) 7.55 (3.1to14.15) 0.001 IL-6 levels (Median, IQR) pg/ml 139 (10.2 to 1.16) 1,012 (486 to 2,862) < 0.0001 WBC (Median, IQR) ×10 9 / L 7.01 (5.92 to 8.1) 6.635 (5.488 to 7.6) 0.09 Neutrophil (Median, IQR) ×10 9 / L 3.325 (2.75 to 4.33) 3.45 (2.81 to 4.48) 0.68 Eosinophil (Median, IQR) ×10 9 / L 0.17(0.08 to 0.27) 0.185(0.12 to 0.3) 0.27 Monocyte (Median, IQR) ×10 9 / L 0.43(0.29 to 0.56) 0.45 (0.33 to 0.58) 0.40 Lymphocyte (Median, IQR) ×10 9 / L 2.810(2.31 to 3.32) 2.545(2.03 to 3.12) 0.05 Discussion In this randomized, open labelled clinical trial, we evaluated the efficacy of DK in reducing symptoms associated with COVID-19 and inflammatory mediators and its safety. We found that DK was well tolerated, with no adverse effects and it significantly reduced the proportion of patients who had cough and symptoms of cold at day 8 since onset of illness, while also significantly reducing the duration of cough. Importantly, there was a significant reduction in CRP and IL-6 levels in those given DK compared to those who were in the control arm. CRP has shown to be significantly elevated in patients with severe COVID-19 and has shown to be elevated during early illness, in those who proceed to develop severe disease [21, 22]. IL-6 is shown to be significantly elevated in patients who develop severe clinical disease [23] and IL-6 receptor blockers were shown to improve survival in critically ill patients [24]. Therefore, 4 to 5 days of treatment with DK during early illness, significantly reduced both CRP and IL-6, on day 8 since onset of illness, which suggests that DK could have potent immunomodulatory properties. Licorice ( Glycyrrhiza glabra ) is one of the main ingredients in DK, which contains many different types of flavonoids which have shown to have antiviral, anti-inflammatory and antitumor activities[25]. Licorice had been reported to be used in China during the early COVID-19 outbreak in over 85% of patients [26] as it was found to show some benefit during the earlier SARS outbreak in 2003 [27]. Licorice was shown to significantly reduce replication of the SARS-COV-1 virus, in vitro , with higher inhibition levels than ribavirin, 6-azauridine, pyrazofurin and mycophenolic acid [28]. It was also shown to reduce the liver damage in chronic hepatitis C infection, inhibit HIV virus replication in mononuclear cells and was shown to reduce expression of TMPRSS2, which is required for cleaving the S1 and S2 subunits in SARS-CoV-2 [29, 30]. Dolichos biflorus , which is another ingredient of DK, showed to significantly reduce carrageenan-induced inflammation in rat models [31] and was shown to have a protective effect against development of peptic ulcers [32]. Pterocarpus santalinus and Santalum album , which are two other ingredients, have also shown to have certain anti-inflammatory, antimicrobial properties in vitro and in some animal models [33]. Savinin and calocedrin, which are two of the active compounds isolated Pterocarpus santalinus from were shown to reduce LPS induced TNFα production from murine macrophage cells lines [34]. Pterostilbene, another compound isolated from Pterocarpus santalinus displayed strong antiviral activities against the SARS-CoV-2 in Vero cell lines up to 48 hours post-infection [35]. 145 active constituents have been isolated from Acorus calamus Linn (Calamus), which is another ingredient of DK, which was shown to reduced oxidative stress and many anti-inflammatory, immunomodulatory and cardioprotective effects [36]. Therefore, DK appears to be composed of many types of ingredients, which have many antiviral, anti-inflammatory and immunomodulatory effects individually. Although the mechanism of action of DK in many of the diseases it has been used in the treatment so far is unknown, it is possible that there is a varied combination of different antiviral and immunomodulatory properties of DK, which should be further investigated. One of the limitations of the trial had to be an open labelled trial, as it was not possible to develop a placebo, with similar taste and characteristics of DK. Therefore, there could have been some bias in reporting symptoms such as cough, features of cold and the presence and absence of certain symptoms in the patients in the DK arm. However, DK only appeared to reduce the presence of cough and features cold and there was no difference in the presence of myalgia, anosmia, loss of appetite or sore throat. Since the safety of DK in patients with COVID-19 is established, it would be important to conduct placebo-controlled trials in future, to mitigate such bias. However, the effects of DK on CRP and IL-6 levels is unlikely to be due to any bias, as these were laboratory assays conducted by individuals who were not involved in the trial and had no knowledge of the samples belonging to the DK or control arm. Although none of the patients in the control arm or the DK arm developed severe clinical disease, since DK appears to alleviate certain symptoms associated with COVID-19, while reducing inflammatory mediators, it would be important to further evaluate the mechanisms of its action and the effectiveness of DK in reducing clinical disease severity in large multi-center clinical trials. In summary, the polyherbal preparation DK appears to be well tolerated in patients with COVID-19 and significantly reduced the presence of cough by day 8 since the onset of illness and the duration of cough. It also significantly reduced the CRP levels and serum IL-6 levels in patients with acute COVID-19. DK appears to have some effect in reducing symptoms and inflammatory mediators in patients with COVID-19 and it would be important to further evaluate the efficacy and mechanisms of action. Abbreviations CRP: C-reactive protein DK: Desadun Kalka IQR: Inter quartile range VOC: Variant of concern Declarations Funding Funding was provided by the Allergy Immunology and Cell Biology Unit, Department of Immunology and Molecular Medicine, University of Sri Jayewardenepura and the Bandaranaike Memorial Ayurvedic Research Institute, Sri Lanka. Author Contribution Conceptualization: RT, SU, GNMTrial design: RT, SU, AW, GNMProject management and resources: AW, CJ, GAFunding: CJ, GNM, GALaboratory assays: CJ, GNMAnalysis: RT, SU, GNMWriting the manuscript: RT, SU, GNM Acknowledgement We are grateful to the staff at the National Institute of Infectious Disease and the Department of Ayurveda Sri Lanka Data Availability The data supporting the conclusions of this article are included within the article and supporting files (supplementary table 1). References Andrews HS, Herman JD, Gandhi RT. Treatments for COVID-19. 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A public survey of traditional, complementary and integrative medicine use during the COVID-19 outbreak in Hong Kong. PloS one. 2021;16(7):e0253890; doi: 10.1371/journal.pone.0253890. Weragoda PB. The traditional system on medicine in Sri Lanka. J Ethnopharmacol. 1980;2(1):71-3; doi: 10.1016/0378-8741(80)90033-1. Ayurveda Do. Ayurveda Pharmacopeia. Department of Ayurveda; 1970. Amarasinghe APGM, M.G.U: Preliminary study of anti-inflammatory effect of Ayurvedic recipe, Rathakalka. In. Edited by Science SLAftAo: Proceedings of the 56th Annual Session of the Sri Lanka Association for the Advancement of Science; 2000: 42. Amarasinghe APGN, B.M.: Antipyretic effect of an Ayurvedic recipe Rathakalka. In: Proceedings of the 59th Annual Session of the Sri Lanka Association for the Advancement of Science. Colombo; 2003. Amarasinghe APG, Widanapathirana, S. Preliminary study of anti- bacterial effect of an Ayurvedic recipe Rathakalka. Indian journal of Research in Ayurvda and Siddha. 2005;4:1-5. WHO: WHO establishes the Global Centre for Traditional Medicine in India. In: Maximizing potential of traditional medicines through modern science and technology. World Health Organization; 2022. WHO: Clinical management of severe acute respiratory infection when novel coronavirus (‎‎‎‎‎‎2019-nCoV)‎‎‎‎‎‎ infection is suspected: interim guidance. In.: WHO; 2020. Ferreira-da-Silva R, Ribeiro-Vaz I, Morato M, Junqueira Polonia J. A comprehensive review of adverse events to drugs used in COVID-19 patients: Recent clinical evidence. European journal of clinical investigation. 2022:e13763; doi: 10.1111/eci.13763. Sharifpour M, Rangaraju S, Liu M, Alabyad D, Nahab FB, Creel-Bulos CM, et al. C-Reactive protein as a prognostic indicator in hospitalized patients with COVID-19. PloS one. 2020;15(11):e0242400; doi: 10.1371/journal.pone.0242400. Pepys MB. C-reactive protein predicts outcome in COVID-19: is it also a therapeutic target? Eur Heart J. 2021;42(23):2280-3; doi: 10.1093/eurheartj/ehab169. Dayarathna S, Jeewandara C, Gomes L, Somathilaka G, Jayathilaka D, Vimalachandran V, et al. Similarities and differences between the 'cytokine storms' in acute dengue and COVID-19. Sci Rep. 2020;10(1):19839; doi: 10.1038/s41598-020-76836-2. Investigators R-C, Gordon AC, Mouncey PR, Al-Beidh F, Rowan KM, Nichol AD, et al. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. The New England journal of medicine. 2021;384(16):1491-502; doi: 10.1056/NEJMoa2100433. Wang L, Yang R, Yuan B, Liu Y, Liu C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm Sin B. 2015;5(4):310-5; doi: 10.1016/j.apsb.2015.05.005. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. Int J Biol Sci. 2020;16(10):1708-17; doi: 10.7150/ijbs.45538. Hsu CH, Hwang KC, Chao CL, Chang SG, Ho MS, Chou P. Can herbal medicine assist against avian flu? Learning from the experience of using supplementary treatment with Chinese medicine on SARS or SARS-like infectious disease in 2003. J Altern Complement Med. 2006;12(6):505-6; doi: 10.1089/acm.2006.12.505. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003;361(9374):2045-6; doi: 10.1016/s0140-6736(03)13615-x. Armanini D, Fiore C, Bielenberg J, Sabbadin C, Bordin L. Coronavirus-19: Possible Therapeutic Implications of Spironolactone and Dry Extract of Glycyrrhiza glabra L. (Licorice). Frontiers in pharmacology. 2020;11:558418; doi: 10.3389/fphar.2020.558418. Murck H. Symptomatic Protective Action of Glycyrrhizin (Licorice) in COVID-19 Infection? Frontiers in immunology. 2020;11:1239; doi: 10.3389/fimmu.2020.01239. Mathew LE, Sindhu G, Helen A. Dolichos biflorus exhibits anti-inflammatory and antioxidant properties in an acute inflammatory model. J Food Drug Anal. 2014;22(4):455-62; doi: 10.1016/j.jfda.2014.02.002. Tovey FI, Capanoglu D, Langley GJ, Herniman JM, Bor S, Ozutemiz O, et al. Dietary Phytosterols Protective Against Peptic Ulceration. Gastroenterology Res. 2011;4(4):149-56; doi: 10.4021/gr328w. Bulle S, Reddyvari H, Nallanchakravarthula V, Vaddi DR. Therapeutic Potential of Pterocarpus santalinus L.: An Update. Pharmacogn Rev. 2016;10(19):43-9; doi: 10.4103/0973-7847.176575. Cho JY, Park J, Kim PS, Yoo ES, Baik KU, Park MH. Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation. Biological & pharmaceutical bulletin. 2001;24(2):167-71; doi: 10.1248/bpb.24.167. Ter Ellen BM, Dinesh Kumar N, Bouma EM, Troost B, van de Pol DPI, van der Ende-Metselaar HH, et al. Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air-Liquid Interface Cultured Human Primary Bronchial Epithelial Cells. Viruses. 2021;13(7); doi: 10.3390/v13071335. Sharma V, Sharma R, Gautam DS, Kuca K, Nepovimova E, Martins N. Role of Vacha (Acorus calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study. J Clin Med. 2020;9(4); doi: 10.3390/jcm9041176. Additional Declarations No competing interests reported. Supplementary Files Supplementaryinformationtrialprotocol.docx Supplementarytable1.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5966181","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":419078677,"identity":"63579427-9b57-462b-bf39-59112431a18d","order_by":0,"name":"Rameeladevi Thatparan","email":"","orcid":"","institution":"Bandaranaike Memorial Ayurveda Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Rameeladevi","middleName":"","lastName":"Thatparan","suffix":""},{"id":419078678,"identity":"24db255a-309d-4067-950a-45639d06bbdc","order_by":1,"name":"Sudharma Umayangani","email":"","orcid":"","institution":"Bandaranaike Memorial Ayurveda Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Sudharma","middleName":"","lastName":"Umayangani","suffix":""},{"id":419078679,"identity":"a66b5cc1-a591-4a42-8317-09b57f6d3e0b","order_by":2,"name":"Gunapala Amarasinghe","email":"","orcid":"","institution":"Bandaranaike Memorial Ayurvedic Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Gunapala","middleName":"","lastName":"Amarasinghe","suffix":""},{"id":419078680,"identity":"1d0d598e-5bdf-46e8-a5b2-3294a939a632","order_by":3,"name":"Ananda Wijewickrama","email":"","orcid":"","institution":"National Institute of Infectious Diseases","correspondingAuthor":false,"prefix":"","firstName":"Ananda","middleName":"","lastName":"Wijewickrama","suffix":""},{"id":419078681,"identity":"b18aa78a-fa98-4d27-ac02-52d252698c73","order_by":4,"name":"Chandima Jeewandara","email":"","orcid":"","institution":"University of Sri Jayawardanapura","correspondingAuthor":false,"prefix":"","firstName":"Chandima","middleName":"","lastName":"Jeewandara","suffix":""},{"id":419078682,"identity":"3b311d68-96d7-4e45-a222-bc4a7306e796","order_by":5,"name":"Gathsaurie Neelika Malavige","email":"data:image/png;base64,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","orcid":"","institution":"University of Sri Jayawardanapura","correspondingAuthor":true,"prefix":"","firstName":"Gathsaurie","middleName":"Neelika","lastName":"Malavige","suffix":""}],"badges":[],"createdAt":"2025-02-05 13:38:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5966181/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5966181/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":77313290,"identity":"4a71ed76-b639-4bce-884b-2e77aeb9ea4b","added_by":"auto","created_at":"2025-02-27 10:16:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39884,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study showing recruitment to the DK arm and the control arm of treatment. 244 individuals were assessed for eligibility and randomised. 11 individuals in the DK arm and 21 individuals in the control arm were lost to follow up.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5966181/v1/dd851d8dfc36d713e8cb5278.png"},{"id":77316366,"identity":"8edb305b-67e9-4f47-9cca-c70eb52a45c8","added_by":"auto","created_at":"2025-02-27 10:48:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":902100,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5966181/v1/5f8b7256-8003-40a8-a004-ea77adf6dd85.pdf"},{"id":77316045,"identity":"87c15f15-45c8-4860-bd5f-59685da06f08","added_by":"auto","created_at":"2025-02-27 10:40:37","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":79514,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryinformationtrialprotocol.docx","url":"https://assets-eu.researchsquare.com/files/rs-5966181/v1/0fdcdbeea49f6f42dbc84e9e.docx"},{"id":77315038,"identity":"ac892d5e-8f2a-4d2c-8c16-94307c7d121a","added_by":"auto","created_at":"2025-02-27 10:32:37","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":105368,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5966181/v1/fc1299c3177dd03aa694a112.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Preliminary evaluation of the efficacy and safety of a traditional poly-herbal preparation “Desadun Kalka” in reducing symptoms and inflammatory mediators in patients with acute COVID-19","fulltext":[{"header":"Background","content":"\u003cp\u003eDuring the COVID-19 pandemic many treatments such as antivirals, monoclonal antibodies and immunomodulatory treatments were developed within a very short time span with hundreds of clinical trials being conducted globally [1]. Clinical trials for COVID-19, included antiviral drugs such as hydroxychloroquine, lopinavir-ritonavir, molnupiravir and the nirmatrelvir plus ritonavir combination and immunomodulatory drugs such as dexamethasone, IL-6 antagonists and Janus kinase inhibitors [1\u0026ndash;4]. Many trials conclusively showed that while hydroxychloroquine and lopinavir-ritonavir did not seem to reduce disease severity or hospitalization [2, 5], molnupiravir reduced hospitalization and death in unvaccinated adults [3] and the nirmatrelvir plus ritonavir combination reduced progression to severe disease [4]. However, hydroxychloroquine was shown to offer moderate benefit in preventing COVID-19 when taken as a prophylactic treatment [6]. Immunomodulators such as dexamethasone were shown to significantly reduce the 28-day mortality in those with moderate to severe COVID-19 requiring oxygen [7], while IL-6 antagonists were shown to decrease mortality for critically ill patients requiring oxygen and receiving dexamethasone [1]. Apart from development of new therapeutics and repurposing existing therapies for COVID-19, several countries reported the use of traditional medicines [8, 9].\u003c/p\u003e \u003cp\u003eBy the end of 2020 over 3600 traditional drugs were undergoing clinical trials for COVID-19 alone in India [9]. Many of these drugs that underwent clinical trials in India and China, have been used for centuries, and have shown to have antiviral or immunomodulatory properties [9, 10]. Possibly as traditional medicine in ingrained in many Asian cultures, a significant proportion of individuals in Asia were found to use traditional medicine in the prevention and treatment of COVID-19 [11, 12]. Traditional medicine has been practiced for centuries in Sri Lanka, and many types of traditional medicine was used for treatment of COVID-19, during the pandemic [13]. However, many of these treatment methods were not formally assessed for their effectiveness in reducing COVID-19 clinical disease severity and complications.\u003c/p\u003e \u003cp\u003eOne of the poly-herbal preparations that have been used as an immunomodulator is Desadun Kalka (DK), which has been used for the prevention of respiratory infections, skin rashes and as a curative treatment for fever, inflammation, respiratory diseases and various skin diseases [14, 15]. DK was shown to reduce yeast induced elevation of body temperature in Wistar rats [16] and was also have antimicrobial effects in bacterial cultures of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, and Listeria monoytogenes [17]. Although DK has been used for centuries, even in infants, the efficacy of this polyherbal preparation has not been assessed. As it is estimated that 80% of the global population use traditional medicine, with 170 of the 194 member states of the WHO regularly using them [18], it was important to evaluate the efficacy of these medicine in the treatment of COVID-19. Therefore, to evaluate the possible efficacy and safety of DK in treatment of COVID-19, we carried out a phase 2, randomized, open labelled clinical trial in Sri Lanka, to determine the efficacy of DK in reducing symptoms and inflammatory mediators in patients with COVID-19.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Design and Oversight\u003c/h2\u003e\n \u003cp\u003eThis study was a randomized, open labeled clinical trial, consisting of two arms, where the test group were given DK along with standard treatment and the control group was given standard management recommended by the Ministry of Health Sri Lanka ( please see supplementary data for trial protocol). The study was carried out at the National Institute of Infectious Disease (NIID), Angoda, Sri Lanka, during April 2021 to December 2021. The ethical approval for this clinical trial was obtained from the Ethics Review Committee of University of Sri Jayewardenepura (Covid 15/20) and the trial was registered at the Sri Lanka Clinical trial registry on the 1st of March 2021, International Clinical Trial Registration Platform (SLCTR/2021/005: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://slctr.lk/trials/slctr-2021-005\u003c/span\u003e\u003c/span\u003e). All individuals gave informed written consent and all methods involving human patients were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003ePatient recruitment and follow-up\u003c/h3\u003e\n\u003cp\u003ePatients who were confirmed to have COVID-19 following a positive RT-qPCR result for the presence of SARS-CoV-2 virus, and a duration of illness of \u0026le;\u0026thinsp;4 days were included following informed written consent. The day of onset of illness was defined as the day of onset of symptoms. The pregnant and breast-feeding mothers, patients who were unable to take the drug orally, those with chronic liver disease or kidney disease and those who had severe and moderate COVID-19 illness according to the WHO COVID-19 disease severity classification [19] were excluded from the study at the initial assessment.\u003c/p\u003e\n\u003cp\u003eThe medical personnel managing the patients in the wards recorded the data on the patients\u0026rsquo; clinical records, assessed the patients for clinical disease severity, and decided on the management of the patients. The investigators who handed out the treatment did not have any role in recording the clinical data on the patients\u0026rsquo; records or in the management of the patients. The investigators involved in dispensing the drug and collecting the data, obtained all data from the patient\u0026rsquo;s clinical records. All clinical features were recorded including any adverse effects that could be related to the drug. The haematological and biochemical parameters were recorded from the laboratory results entered in the clinical records. The data was obtained on the day of recruitment and on day 10 of illness (and not day 10 since recruitment). Although PCRs to determine the viral loads on day of recruitment and again on day 10 since recruitment were to be done, this could not be carried out, as hospital and the laboratories involved in this study was overburdened during the massive COVID 19 outbreak due to delta variant that was experienced in Sri Lanka from July to October 2021.\u003c/p\u003e\n\u003ch3\u003eRandomization\u003c/h3\u003e\n\u003cp\u003ePatients who gave consent for the study were randomized to receive DK or be in the control arm in 1:1 ratio, which was decided using a computerized random number generator of sequential patients who were admitted to the COVID-19 wards in the hospital. Those in the DK arm were given 1250mg of DK three times a day orally, starting from the day of recruitment up to 4 to 5 days (median 4 days, IQR 4 to 5 days) along with the standard treatment. Although the study was planned to give the patients, DK for 10 days, as the patients were discharged from hospital much earlier due to high number of hospital admissions, they were only given the drug for 4 to 5 days, since the date of recruitment (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The control group was given standard management as per the Ministry of Health COVID-19 management guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Baseline characteristics of the patients at the time of recruitment in the treatment arm and the control arm\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003eDK arm\u003c/p\u003e\n \u003cp\u003eN = 76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003eControl arm\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN= 76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eAge (median, \u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e(47.5, SD\u0026plusmn;14.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e(46, SD\u0026plusmn;18.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 85.4369%;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eMale (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e44 (57.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e38 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eFemale (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e32 (42.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e38 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eDuration of illness on day of recruitment\u003c/p\u003e\n \u003cp\u003eMean (\u0026plusmn;SD) days\u003c/p\u003e\n \u003cp\u003eMedian (IQR) days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.4 (0.74)\u003c/p\u003e\n \u003cp\u003e4 (3 to 4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.4 (0.75)\u003c/p\u003e\n \u003cp\u003e4 (3 to 4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eCT value (Viral load)\u003c/p\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e15 (14 to 18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e17 (15 to 20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eComorbidities: N (%)\u003c/p\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003cp\u003eDyslipidaemia\u003c/p\u003e\n \u003cp\u003eIschaemic heart disease\u003c/p\u003e\n \u003cp\u003eAsthma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eLaboratory parameters - on Admission\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eWBC (Median, IQR) \u0026times;10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e7.01 (5.50 to 8.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e6.205 (4.76 to 8.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eNeutrophil (Median, IQR) \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e3.73 (2.85 to 5.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e3.720 (2.525 to 4.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eEosinophil (Median, IQR) \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e0.09 (0.019 to 0.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e0.1 (0.04 to 0.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eMonocyte (Median,IQR) \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e0.59 (0.46 to -0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e0.55(0.45 to 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eLymphocytes (Median, IQR) \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e2.045 (1.58 to 2.788)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e1.79 (1.278 to 2.628)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eAST (Median, IQR) U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e34 (24.15 to 47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e32.88 (25 to 46.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eALT (Median, IQR) U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e37 (24.25 to 63.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e35.5 (26 to 56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.9515%;\"\u003e\n \u003cp\u003eCRP (Median, IQR) mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.2136%;\"\u003e\n \u003cp\u003e13.15(6.3 to 24.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2718%;\"\u003e\n \u003cp\u003e17.35(4.575 to 26.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.5631%;\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003eThe trial drug\u003c/h3\u003e\n\u003cp\u003eDesadun Kalka (DK) is a traditional polyherbal preparation that has been used for centuries in ayurvedic medicine. This Kalka was prepared according to the procedure mentioned in Ayurveda Pharmacopoeia DK is composed of \u003cem\u003eDolichos biflorus\u003c/em\u003e Linn (Horse gram), \u003cem\u003eAcorus calamus\u003c/em\u003e Linn (Calamus), \u003cem\u003eGlycyrrhiza glabra\u003c/em\u003e Linn (Licorice), \u003cem\u003ePterocarpus santalinus\u003c/em\u003e Linn (Red Sandalwood), \u003cem\u003eSantalum album\u003c/em\u003e Linn (Suduhandun), and Rock salt. All these ingredients were identified and authenticated by the botany division and quality assurance laboratory of Bandaranaike Memorial Ayurvedic Research Institute (BMARI). The physical impurities of the herbal ingredients were removed washed and dried in the shade and disintegrated individually into fine powder. These individual powders were sieved separately through 0.12mm mesh. The fine powder of the above herbal ingredients was taken in equal amounts and mixed together. The rock salt and was dissolved in lime juice. The salt and lime juice was mixed well with fine powders of all five herbal ingredients and kept for 24 hours in the clay pot at the room temperature. Finally, the mixture was grounded together into the form of paste to form the drug. DK was prepared with an equal consistency in the BMARI pharmacy and stored in prepacked envelopes in a designated cupboard, at room temperature. The final drug preparation was dispensed as a 1250mg single dose.\u003c/p\u003e\n\u003ch3\u003eTrial end points\u003c/h3\u003e\n\u003cp\u003eThe primary objective in this study was to evaluate the efficacy of \u0026lsquo;Desadun Kalka (DK)\u0026rsquo; in reducing the severity and duration of symptoms in COVID-19 infection. The secondary objectives were to study the safety of DK in patients with COVID-19, by assessing the haematological and biochemical parameters of the patients. In addition, the other secondary objectives were to assess the effects of DK on the duration of clinical symptoms using the WHO ordinal outcome scale and to determine if DK reduced viral loads. The day of onset of illness was defined as the day of onset of symptoms.\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eAssays to determine serum IL-6 levels\u003c/h2\u003e\n \u003cp\u003eSerum samples were diluted in the sample diluent (SD13) and loaded into cartridges with relevant controls for high and low controls. Multiplex and single plex ELLA cartridges were run for IL-6, (Protein Simple, USA, SPCKB-PS-000276) with their high and low control concentrates IL-10 IL-6 (Cat:895003) in ELLA analyzer (ELLA 19050375 version 3.4.0.52, Protein Simple, USA) Measurements were taken in triplicates in separate glass nanoreactors (GNRs) for each cytokine of each sample in pg/ml.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003eThe sample size was calculated to determine the efficacy of DK in reducing the duration taken for relief in symptoms (fever, cough, sore throat and anosmia) between the treatment group and the control group. It was assumed that the variance (duration of symptoms) was 6.5 days with a dropout rate was 5%. According to detect a difference in the two groups with a significance level of 5% and a power of 1 - \u0026beta;, it was calculated to be 76 in each arm (total 152 patients).\u003c/p\u003e\n \u003cp\u003eThe primary end point of the trial was the reduction in number of individuals who developed severe disease a reduction in the symptoms and duration of symptoms (cough, sore throat, fever, anosmia) associated with COVID-19. The secondary endpoint that was used in the analysis was the changes in biochemical and haematological parameters (to assess safety) and a reduction in inflammatory mediators (CRP and IL-6 levels). Statistical analysis was performed using Graphpad PRISM version 8.3. The differences in duration of different symptoms, haematological, biochemical parameters and inflammatory markers in samples collected at the time of recruitment (baseline) and at 8 day from the onset of illness were done using the two tailed Mann-Whitney U-test. The degree of association between inflammatory markers and biochemical and haematological parameters was analyzed using Spearman correlation coefficient test.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe baseline characteristics of patients who were assigned to receive DK and who were randomized to be in the control arm are shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There was no difference in the baseline characteristics except for the Ct values in the SARS-CoV-2 specific RT-qPCR, where those who were assigned to the DK arm were found to have significantly lower (p\u0026thinsp;=\u0026thinsp;0.007) Ct values (higher viral loads) than those who were in the control arm. 76 patients in the DK arm completed 4 to 5 days (median 4 days, IQR 4 to 5 days) of DK and standard treatment, while 76 patients in the control arm received standard treatment for the same duration. According to admission policy for COVID-19 in Sri Lanka, anyone with COVID-19 who wished to get admitted to hospital, even if they had mild illness could do so, and therefore, all those who were recruited to our study had mild illness.\u003c/p\u003e \u003cp\u003eThe baseline characteristics at the time of recruitment to the study were also assessed (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and there were no significant differences in the baseline clinical features at the time or enrollment.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSymptoms at the time of recruitment in patients who were in the treatment arm and control arm\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical symptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDK arm\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl arm\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRelative risk (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43 (56.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (56.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.75 to 1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCough\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63 (82.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (71.05%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.979 to 1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCold\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28 (36.84%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (32.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.726 to 1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (19.73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (26.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.417 to 1.338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (30.26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (30.26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.618 to 1.617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSore throat\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (15.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.536 to 2.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhoea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.06 to 3.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (22.36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.507 to 1.574\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26 to infinity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnosmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.57 to 7.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss of appetite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2482 to 2.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAdverse events\u003c/h2\u003e \u003cp\u003eAll adverse events were recorded and reported as classified by using the Common Terminology Criteria for adverse events, which has been used in reporting of adverse events in previous drug trials for COVID-19 [20]. None of the patients developed pneumonia or multi-organ failure (this was an exclusion criteria) and none of the patients succumbed to their illness (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There was no difference in the adverse events reported in the DK arm compared to the control arm.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse reactions observed in patients in the treatment arm and control arm since day 10 since onset of illness\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSide effect\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDK arm\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl arm\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRelative risk\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value(\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhoea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26 to infinity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26 to infinity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 to 0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatitis (ALT\u0026thinsp;\u0026gt;\u0026thinsp;250/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (Median, IQR)\u003c/p\u003e \u003cp\u003e(\u0026lt;\u0026thinsp;40 U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34, (24.3\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.88 (25 to 46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.92 to 1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (Median, IQR)\u003c/p\u003e \u003cp\u003e(\u0026lt;\u0026thinsp;55U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37, (24.5\u0026ndash;66.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.5 (26- to 56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.40 to 1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow white cell counts (\u0026lt;\u0026thinsp;4\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 to 1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow platelet counts (\u0026lt;\u0026thinsp;50\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eOverall efficacy of DK\u003c/h2\u003e \u003cp\u003eTo assess the efficacy of DK compared to standard treatment alone the differences in clinical and laboratory features of those on DK and the control arm were compared. None of the patients in the DK arm or control arm had fever by day 8 since onset of illness and there was no difference in the duration of fever in both arms (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Interestingly, those on the DK arm were significantly less likely to have symptoms of a cold (p\u0026thinsp;=\u0026thinsp;0.006) and a cough (p\u0026thinsp;=\u0026thinsp;0.006) on day 8 since onset of illness compared to the control group. Those who were on DK also had a significantly shorter duration of a cough (p\u0026thinsp;=\u0026thinsp;0.006), compared to the control group (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, there was no difference in the duration of a sore throat, myalgia, anosmia and loss of appetite in both groups. None of the patients in the DK arm and 2 patients in the control arm developed difficulty in breathing, which was not significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical symptoms on day 8, since onset of illness in those in the treatment arm and control arm\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical symptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDK arm\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl arm\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRelative risk (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value (\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of Fever: N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of fever (Median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0 to 5.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (0 to 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of symptoms of cold: N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (6.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 to 0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of cold (Median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0 to 5.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0 to 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of cough: N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (9.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 to 0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of cough (Median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (4.25 to 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (0 to 9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifficulty in breathing \u0026ndash;N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 to 1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of difficulty in breathing (Median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0 to 4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0 to 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of Sore throat \u0026ndash; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of sore throat (Median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0, 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0, 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of myalgia \u0026ndash; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.04%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of myalgia (Median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0, 0 to 3.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0, 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of anosmia \u0026ndash; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26 to infinity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of anosmia (Median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0, 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0, 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss of Appetite \u0026ndash; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 to 1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of LOA (Median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0, 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0, 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe CRP levels (p\u0026thinsp;=\u0026thinsp;0.001) and the serum IL-6 levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) were significantly lower on day 8 of the illness in those who were in the DK arm compared to those in the control arm (Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). There was no difference in the total white cell counts, neutrophil, lymphocyte, monocyte and eosinophil count in those in the DK arm compared to the control arm. Serum fibrinogen levels, procalcitonin, D-dimer levels, ferratin and lactic dehydrogenase levels and chest imaging was only done on selected patients who develop severe disease and are admitted to the intensive care units or high dependency units and were not carried out in any of these patients included in the study.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHaematological and inflammatory markers in the treatment arm and the control arm on day 8 since onset of illness\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDK arm\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl arm\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (Median, IQR) mg/dl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.25 (3.1 to 7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.55 (3.1to14.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6 levels (Median, IQR) pg/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139 (10.2 to 1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,012 (486 to 2,862)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (Median, IQR) \u0026times;10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.01 (5.92 to 8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.635 (5.488 to 7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil (Median, IQR) \u0026times;10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.325 (2.75 to 4.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.45 (2.81 to 4.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEosinophil (Median, IQR) \u0026times;10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.17(0.08 to 0.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.185(0.12 to 0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonocyte (Median, IQR) \u0026times;10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.43(0.29 to 0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.45 (0.33 to 0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocyte (Median, IQR) \u0026times;10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.810(2.31 to 3.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.545(2.03 to 3.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this randomized, open labelled clinical trial, we evaluated the efficacy of DK in reducing symptoms associated with COVID-19 and inflammatory mediators and its safety. We found that DK was well tolerated, with no adverse effects and it significantly reduced the proportion of patients who had cough and symptoms of cold at day 8 since onset of illness, while also significantly reducing the duration of cough. Importantly, there was a significant reduction in CRP and IL-6 levels in those given DK compared to those who were in the control arm. CRP has shown to be significantly elevated in patients with severe COVID-19 and has shown to be elevated during early illness, in those who proceed to develop severe disease [21, 22]. IL-6 is shown to be significantly elevated in patients who develop severe clinical disease [23] and IL-6 receptor blockers were shown to improve survival in critically ill patients [24]. Therefore, 4 to 5 days of treatment with DK during early illness, significantly reduced both CRP and IL-6, on day 8 since onset of illness, which suggests that DK could have potent immunomodulatory properties.\u003c/p\u003e \u003cp\u003eLicorice (\u003cem\u003eGlycyrrhiza glabra\u003c/em\u003e) is one of the main ingredients in DK, which contains many different types of flavonoids which have shown to have antiviral, anti-inflammatory and antitumor activities[25]. Licorice had been reported to be used in China during the early COVID-19 outbreak in over 85% of patients [26] as it was found to show some benefit during the earlier SARS outbreak in 2003 [27]. Licorice was shown to significantly reduce replication of the SARS-COV-1 virus, \u003cem\u003ein vitro\u003c/em\u003e, with higher inhibition levels than ribavirin, 6-azauridine, pyrazofurin and mycophenolic acid [28]. It was also shown to reduce the liver damage in chronic hepatitis C infection, inhibit HIV virus replication in mononuclear cells and was shown to reduce expression of TMPRSS2, which is required for cleaving the S1 and S2 subunits in SARS-CoV-2 [29, 30].\u003c/p\u003e \u003cp\u003e \u003cem\u003eDolichos biflorus\u003c/em\u003e, which is another ingredient of DK, showed to significantly reduce carrageenan-induced inflammation in rat models [31] and was shown to have a protective effect against development of peptic ulcers [32]. \u003cem\u003ePterocarpus santalinus\u003c/em\u003e and \u003cem\u003eSantalum album\u003c/em\u003e, which are two other ingredients, have also shown to have certain anti-inflammatory, antimicrobial properties \u003cem\u003ein vitro\u003c/em\u003e and in some animal models [33]. Savinin and calocedrin, which are two of the active compounds isolated \u003cem\u003ePterocarpus santalinus\u003c/em\u003e from were shown to reduce LPS induced TNFα production from murine macrophage cells lines [34]. Pterostilbene, another compound isolated from \u003cem\u003ePterocarpus santalinus\u003c/em\u003e displayed strong antiviral activities against the SARS-CoV-2 in Vero cell lines up to 48 hours post-infection [35]. 145 active constituents have been isolated from \u003cem\u003eAcorus calamus\u003c/em\u003e Linn (Calamus), which is another ingredient of DK, which was shown to reduced oxidative stress and many anti-inflammatory, immunomodulatory and cardioprotective effects [36]. Therefore, DK appears to be composed of many types of ingredients, which have many antiviral, anti-inflammatory and immunomodulatory effects individually. Although the mechanism of action of DK in many of the diseases it has been used in the treatment so far is unknown, it is possible that there is a varied combination of different antiviral and immunomodulatory properties of DK, which should be further investigated.\u003c/p\u003e \u003cp\u003eOne of the limitations of the trial had to be an open labelled trial, as it was not possible to develop a placebo, with similar taste and characteristics of DK. Therefore, there could have been some bias in reporting symptoms such as cough, features of cold and the presence and absence of certain symptoms in the patients in the DK arm. However, DK only appeared to reduce the presence of cough and features cold and there was no difference in the presence of myalgia, anosmia, loss of appetite or sore throat. Since the safety of DK in patients with COVID-19 is established, it would be important to conduct placebo-controlled trials in future, to mitigate such bias. However, the effects of DK on CRP and IL-6 levels is unlikely to be due to any bias, as these were laboratory assays conducted by individuals who were not involved in the trial and had no knowledge of the samples belonging to the DK or control arm. Although none of the patients in the control arm or the DK arm developed severe clinical disease, since DK appears to alleviate certain symptoms associated with COVID-19, while reducing inflammatory mediators, it would be important to further evaluate the mechanisms of its action and the effectiveness of DK in reducing clinical disease severity in large multi-center clinical trials.\u003c/p\u003e \u003cp\u003eIn summary, the polyherbal preparation DK appears to be well tolerated in patients with COVID-19 and significantly reduced the presence of cough by day 8 since the onset of illness and the duration of cough. It also significantly reduced the CRP levels and serum IL-6 levels in patients with acute COVID-19. DK appears to have some effect in reducing symptoms and inflammatory mediators in patients with COVID-19 and it would be important to further evaluate the efficacy and mechanisms of action.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCRP: C-reactive protein\u003c/p\u003e\n\u003cp\u003eDK: Desadun Kalka\u003c/p\u003e\n\u003cp\u003eIQR: Inter quartile range\u003c/p\u003e\n\u003cp\u003eVOC: Variant of concern\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003e Funding was provided by the Allergy Immunology and Cell Biology Unit, Department of Immunology and Molecular Medicine, University of Sri Jayewardenepura and the Bandaranaike Memorial Ayurvedic Research Institute, Sri Lanka.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: RT, SU, GNMTrial design: RT, SU, AW, GNMProject management and resources: AW, CJ, GAFunding: CJ, GNM, GALaboratory assays: CJ, GNMAnalysis: RT, SU, GNMWriting the manuscript: RT, SU, GNM\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe are grateful to the staff at the National Institute of Infectious Disease and the Department of Ayurveda Sri Lanka\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the conclusions of this article are included within the article and supporting files (supplementary table 1).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAndrews HS, Herman JD, Gandhi RT. 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Gastroenterology Res. 2011;4(4):149-56; doi: 10.4021/gr328w.\u003c/li\u003e\n\u003cli\u003eBulle S, Reddyvari H, Nallanchakravarthula V, Vaddi DR. Therapeutic Potential of Pterocarpus santalinus L.: An Update. Pharmacogn Rev. 2016;10(19):43-9; doi: 10.4103/0973-7847.176575.\u003c/li\u003e\n\u003cli\u003eCho JY, Park J, Kim PS, Yoo ES, Baik KU, Park MH. Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation. Biological \u0026amp; pharmaceutical bulletin. 2001;24(2):167-71; doi: 10.1248/bpb.24.167.\u003c/li\u003e\n\u003cli\u003eTer Ellen BM, Dinesh Kumar N, Bouma EM, Troost B, van de Pol DPI, van der Ende-Metselaar HH, et al. Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air-Liquid Interface Cultured Human Primary Bronchial Epithelial Cells. Viruses. 2021;13(7); doi: 10.3390/v13071335.\u003c/li\u003e\n\u003cli\u003eSharma V, Sharma R, Gautam DS, Kuca K, Nepovimova E, Martins N. Role of Vacha (Acorus calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study. J Clin Med. 2020;9(4); doi: 10.3390/jcm9041176.\u003c/li\u003e\n\u003c/ol\u003e "}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, polyherbal preparation, inflammatory mediators, CRP, IL-6, Desadun Kalka","lastPublishedDoi":"10.21203/rs.3.rs-5966181/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5966181/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: During the COVID-19 pandemic, many traditional herbal medicines were used to treat patients with COVID-19. We sought to determine the efficacy and safety of a traditional polyherbal preparation-Desadun Kalka (DK) in reducing symptoms and inflammatory mediators in patients with COVID-19 in Sri Lanka.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We conducted a phase 2, randomized, open labelled clinical trial, in hospitalized adult patients with a confirmed SARS- COV-2 infection, enrolled within the ≤ 4 days since onset of symptoms. Those in the treatment arm (n=76) were given 1250mg of DK three times a day orally, starting from the day of recruitment, up to 4 to 5 days (median 4 days, IQR 4 to 5 days) along with the standard treatment, while those in the control arm (n=76) were given standard treatment. \u003cstrong\u003eResults:\u003c/strong\u003e Patients in the DK arm and control arm had similar baseline characteristics except for those in the DK arm having significantly lower (p=0.007) Ct values for SARS-CoV-2 specific RT-qPCR than those in the control arm. DK was well tolerated, and no adverse events were reported. Patients in the DK arm were significantly less likely to have symptoms of a cold (p=0.006) and cough (p=0.006) on day 8 since onset of illness compared to the control group and had a significantly shorter duration of a cough (p=0.006). The CRP levels (p=0.001) and the serum IL-6 levels (p\u0026lt;0.0001) were significantly lower on day 8 of the illness in those who were in the DK arm compared to those in the control arm, while there were no differences in other clinical features, or haematological or biochemical parameters in the DK vs control group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: DK appears to have some effect in reducing symptoms and inflammatory mediators in patients with COVID-19 and it would be important to further evaluate the efficacy and mechanisms of action.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e the trial was registered at the Sri Lanka Clinical trial registry on the 1st of March 2021, International Clinical Trial Registration Platform (SLCTR/2021/005: https://slctr.lk/trials/slctr-2021-005 )\u003c/p\u003e","manuscriptTitle":"Preliminary evaluation of the efficacy and safety of a traditional poly-herbal preparation “Desadun Kalka” in reducing symptoms and inflammatory mediators in patients with acute COVID-19","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-27 10:16:33","doi":"10.21203/rs.3.rs-5966181/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2fbf2967-87be-478e-8da8-fdc7d3a8d702","owner":[],"postedDate":"February 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-27T10:16:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-27 10:16:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5966181","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5966181","identity":"rs-5966181","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}