key: cord-0999063-qk5rdwqv authors: Chitra, S.M.; Mallika, P.; Anbu, N.; NarayanaBabu, R.; SugunaBai, A.; David Paul Raj, R.S.; Premnath, D. title: An Open Clinical Evaluation Of Selected Siddha Regimen In Expediting The Management Of Covid-19 –A Randomized Controlled Study date: 2021-01-21 journal: J Ayurveda Integr Med DOI: 10.1016/j.jaim.2021.01.002 sha: bff7a250941e6be9797e48f8ef9dd87f8e04eea2 doc_id: 999063 cord_uid: qk5rdwqv INTRODUCTION: The corona virus disease 2019 (COVID-19), an acute respiratory disease, caused by a novel corona virus (SARS-CoV-2, previously known as 2019-nCoV), obtained worldwide attention. The World Health Organization (WHO) officially declared the Covid-19 epidemic as a public health emergency of international concern. In this review, we explored the potential siddha strategies for covid – 19 infections. Aim and objectives: To evaluate the additional benefits of siddha drugs Vasantha kusumakaram mathirai, Thippili rasayanam, Adathodai manapagu and Kabasura kudineer compared to the allopathic standard of care alone in COVID-19 mild – moderate cases. MATERIALS AND METHODS: The present study was an open label Two arm - randomized controlled interventional clinical study. The Group I patients were assigned to Siddha add on treatment whereas Group II subjects were assigned with standard treatment alone. The patients recruited for the study were Covid 19 RT-PCR +ve patients declared by Tamil Nadu Government and admitted in IPD (in patient ward) at Omandurar Government Medical College Hospital. The sample size was 100 for each group. RESULT: Among the gender distribution observed in Group I and Group II, 71, 69 were males and 29, 31 were females respectively. The mean age of patients was observed as 42.98 in Group I and 45.68 in Group II. The average number of days taken for reduction of symptoms after the treatment was 3.21 and 5.13 in Group I and Group II respectively (n=100). The Group I showed significant results (P<0.001) when compared with Group II. The real – time polymerase chain reaction (RT-PCR) investigation turned negative for 78.33% in Group I and 33.33% in Group II patients after 11-14 days duration of treatment. Similarly, the before and after Computed tomography (CT) chest, Ground glass opacities covid pattern lung involvement percentage showed highly significant reduction (P<0.0001) in Group I, when compared with Group II, which showed significant reduction (P<0.001) for the same. In addition, Neutrophil Lymphocyte Ratio (NLR) ratio, showed significant reduction (P<0.01) when analyzed by Wilcoxon signed rank test. Renal and Liver parameters were observed within the normal limits when analyzed after treatment for 25 samples in Group I. CONCLUSION: Finally, it was concluded that Siddha add on Group showed accelerated recovery for Covid - 19 patients compared to standard treatment Group. The synergistic effect of Siddha add on with standard treatment gave more promising results in the current study of Covid -19. An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID- 19) , has spread throughout China and received worldwide attention. On 30 January 2020, the World Health Organization (WHO) officially declared the Covid -19 epidemics as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory with 55794 deaths had been reported by WHO 1 . In Tamil Nadu a total of 3,67,430 covid cases with death toll to 6340 of which Chennai share was 1,22,757 in total cases and 2501 in death toll. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of covid-19 patients include fever, cough, fatigue, and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antiviral and repurposed drugs are under urgent investigation 2. In this research studies , we explored the potential Siddha strategies for Covid-19 infections. The selected Siddha regimen for covid-19 study comprised Kabasura kudineer and These Siddha medicines had been widely in use for decades in the treatment for the above indicated ailments. Moreover, these medicines are currently in use and dispensed to the patients in all Government Siddha, OPD (out patient department), and IPD (in patient department) wings of Tamil Nadu. The efficacy of the medicines had also been validated scientifically in respiratory and other ailments. [5] [6] [7] [8] [9] [10] [11] The objectives of the present trial was to establish the add on benefit of selected Siddha medicines Vasantha kusumakaram mathirai, Thippili rasayanam, Adathodai manapagu and Kabasura kudineer in the management of Covid -19 diseases as Siddha regimen along with standard of care management compared with patients who have not taken the Siddha medicines but only Standard of care alone. Other concurrent objectives was to evaluate the improvement of Covid symptoms presented in patients, reduction of days in long term hospitalization as well as reduction in case fatality rate. This study was conducted in accordance with the intent and purpose of Good clinical practice guidelines and/or the Declaration of Helsinki, as appropriate. The study was initiated after Sample size and randomization: The sample size was 100 in each group. From the calculated sample size using a power of 80%, each group in the study consisted of 90 subjects giving a total of 180 subjects and an additional 10% drop out rate added with total sample size 100 each. Appropriate corrections were affected after the research instrument was pre tested. Simple random sampling method was employed. The participants were equally allocated to either Group I or Group II treatment group by computer-generated random numbers using the Stat Trek random number generator 12 Exclusion Criteria were Age: Less than 18 and above 60, Pregnancy and lactating mothers, Patients with severe or critical covid-19 infections, Mentally retarded and those who are taking psychiatric drugs, Immuno-compromised patients, Patients with co morbid disease conditions, Other viral pneumonia Patients who have received organ transplantation in the past 6 months or planning surgery were excluded clinically and based on available medical reports. Before conducting the trial, a predesigned, written informed consent form was obtained from the patients by following an explanation about the study in the local language (Tamil) and in English for those who were not familiar in local language. The study adheres to CONSORT guidelines. Withdrawal Criteria: Aggravation of symptoms, Intolerance to drug and development of adverse reactions during drug trial, Occurrence of any other severe illness, Incidence of any acute illness that would warrant other extensive drug treatment during the trial, Withdrawal J o u r n a l P r e -p r o o f proforma towards discontinuation of patients and adverse drug reaction proforma was also designed to record and report any serious adverse event. Data regarding demographic particulars, lab investigation, and drug history of the patients were obtained from them in person and through their case sheets. During follow up period the symptoms were recorded telephonically. After 11-14 days of treatment, clinical assessment was mainly determined by reduction of clinical symptoms and the main parameters used for assessment were, comparing before and after treatment RT-PCR report and CT chest Ground glass opacities covid pattern (GGO) lung involvement percentage 14 . The CT scan findings were confirmed by the Head of the Radiology Department, Government Omandurar Medical College, Chennai-02. The following investigations were also undertaken, a) CBC (complete blood count) b) Blood sugar (fasting and post prandial) c) SpO 2 (oxygen saturation) were taken for all the patients at the time of admission and d) RFT (renal function test) e) LFT (liver function test) for suspected patients who had clinical abnormality with relation to renal and liver diseases at the time of admission and discharge since most of them were discharged based on reduction of symptoms due to pandemic issue. The Group I asymptomatic, mild, moderate patients received Siddha add on treatment. The As secondary outcome measures sub group analysis of male, female and mean age group, symptoms distribution in both groups were studied. Case fatality rate was also documented in both the groups. J o u r n a l P r e -p r o o f The collected data were analysed using Graph Pad Prism software version 5 and SPSS 21.Demographic variables were given in frequency and percentage. Statistical analysis for gender difference was analysed using chi-square test. Age difference and average days of symptom reduction was analysed using student independent t-test. Statistical analysis for RT-PCR evaluation was done using chi-square test and relative risk was given with 95% confidence interval. Student paired t-test was used to analyse CT chest results before and after treatment. Blood investigation parameters before and after treatment were analysed for 25 samples in Siddha add on Group patients using Wilcoxon signed rank test. In order to ascertain if there is any adverse reaction in vital organs like kidney and Liver, Renal and Liver profile were recorded for 25 samples (after treatment) and expressed as mean and SD in Siddha add on Group. A total of 212 subjects were screened for the study of which 200 subjects satisfied the inclusion criteria and 100 patients were allocated to each group in the study. In total 12 subjects dropped out and subsequently for want of resources (due to inadequate bed strength, rest were recommended to covid care centers) sixty were included in Group I (cases) and 30 were included in Group II (control). The enrolment, allocation, follow up and analysis scheme of the trial is depicted through consort flow diagram. (Figure 1 ). The gender distribution was analysed and observed that, in Siddha add on Group among 100 patients, 71were male and 29 were female. In standard treatment Group, among 100 patients analysed during the study period, 69 were male and 31 were female. Hence gender distribution was similar in both the groups according to chi-square test. The mean age of patients was observed as 42.98 in Group I and 45.68 in Group II. There was no significant difference between age group according to student independent t-test. Table I , showed the symptoms of patients at the time of admission in Group I and Group II respectively (n = 100). In Siddha add on Group, the mean value of number of days taken for reduction of symptoms after the treatment was 3.21 and in standard treatment group, the average mean was 5.13. According to chi-square test Siddha add on regimen group showed significant result (P<0.001) when compared with standard treatment group.. Added to this, the average number of days of hospitalization for mild symptom patients was 3-4 days and moderate symptom patients was 4-5 days respectively in Group I(Siddha add on treatment). Similarly, in Group II (standard treatment), 4-5 days for mild symptom patients and 10-11 days for moderate J o u r n a l P r e -p r o o f symptom patients and they were directed to covid care centre for further care. Hence it was concluded that Siddha add on treatment was more effective when compared to standard treatment alone. Table 2 whereas Group II was 66.67 %. So, the difference was statistically significant according to chi square test. Relative risk was 2.09. It shows that Group II positivity was 2 times higher than Group I positivity. Hence, it was concluded that Siddha add on treatment makes the patient noncontagious at earlier days itself when compared to Standard treatment (allopathic) alone. In CT chest findings, Ground glass opacities, covid pattern (GGO) of total lung involvement percentage was taken as parameter and compared before and after treatment in patients of Group I and Group II respectively using student paired t-test. In Siddha add on Group, after CT chest results showed highly significant reduction (P<0.0001) when compared with before CT chest results. In standard treatment Group, the after CT chest results compared with before CT chest results showed significant reduction (P<0.001). The percentage of mean activity (represents the percentage protection of respective drug treated group) observed in Group I was 64.34 and Group II 54.39. Hence it was observed that Siddha add on treatment showed more promising results than standard treatment alone. The Blood investigation parameters, Total count (TC), differential count (DC), Absolute lymphocyte count (ALC), Neutrophil Lymphocyte Ratio (NLR) ratio, Red blood cell (RBC), Haemoglobin (Hb), packed cell volume (PCV), and platelet count were analysed for 25 samples in Siddha add on Group before and after treatment (due to limited health professionals, reagents and lockdown issue we were unable to collect the samples from all patients) and summarized in table 3 using Wilcoxon signed rank test. ALC showed significant improvement P<0.001 and NLR showed significant reduction P<0.01. Platelet count showed improvement in post-test while PCV value remained unaltered in pre and posttest respectively. RBC and Hb showed insignificant reduction in post-test compared to pretest and the P values for these were not significant. There is a general perception that some of the herbal medicines may cause renal or liver function impairment. Therefore, in order to ascertain the safety of Siddha formulations co administered in the present study, Liver The current study concludes that Siddha add on Group showed accelerated recovery for Covid -19 patients compared to standard treatment Group. The synergistic effect of Siddha add on with standard treatment gave more promising results during the entire study period of Covid -19. Furthermore, this present trial throws light on repurposing the existing drugs in traditional Siddha system of medicine to utilize them in the treatment of Covid-19. World Health Organisation, Corona virus disease Covid -19, Dashboard The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak -an update on the status The Siddha Formulary of India, Part I, Department of Health and Family Welfare, Government of India Indian Medicine and Homeopathy Department COVID-19: A promising cure for the global panic Anti-Inflammatory, Antipyretic and Antibacterial Study of Kabasura Kudineer Choornam Management of Chikun Gunya through Ayurveda and Siddha, Central Council For Research in Ayurveda and Siddha, Department of AYUSH, Ministry of Health and Family Welfare, Government of India Anti-Viral Activities and Cytotoxicity Assay of Seed Extracts of Piper longum and Piper nigrum on Human Cell Lines Siddha Medicines for Eraippu Erumal (Bronchial Asthma) -Preliminary Phytochemical and Anti-Microbial Studies Acute and Sub-acute Toxicity study of Venkaraparpam, Dissertaion, Branch VI -Nanju Noolum Maruthuva Neethinoolum A Toxicity study on Linga Chenduram Stat Trek Random number generator Clinical management of COVID -19, Interim guidance, WHO COVID-19 pneumonia: A review of typical CT findings and differential diagnosis Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective World Health Organisation, Corona virus disease Covid -19, Dashboard The Indian express, by Express web desk, Chennai The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak -an update on the status The Siddha Formulary of India, Part I, Department of Health and Family Welfare, Government of India Indian Medicine and Homeopathy Department COVID-19: A promising cure for the global panic Anti-Inflammatory, Antipyretic and Antibacterial Study of Kabasura Kudineer Choornam Management of Chikun Gunya through Ayurveda and Siddha, Central Council For Research in Ayurveda and Siddha, Department of AYUSH, Ministry of Health and Family Welfare, Government of India Scientific evaluation of functional groups presence in Siddha Herbo mineral formulation "Vasantha Kusumakaram Mathirai" using FTIR spectrometer Evaluation of Bronchodilator activity of Siddha Herbo Mineral Drug Vasanthakusumakara Mathirai by exposing Guinea pigs in Histamine Aerosol Novel action of ThippiliRasayanam -Siddha drug aganist respiratory pathogens Anti Inflammatory and Antiseptic Activity of Ancient Traditional Siddha Drug Thippili Rasayanam in Paediatric Care Anti-Viral Activities and Cytotoxicity Assay of Seed Extracts of Piper longum and Piper nigrum on Human Cell Lines A Combination of NilavembuKudineer and AdathodaManapagu in the Management of Dengue Fever Medicinal uses and Pharmacological activity of AdhatodaVasica Siddha Medicines for Eraippu Erumal (Bronchial Asthma) -Preliminary Phytochemical and Anti-Microbial Studies Acute and Sub-acute Toxicity study of Venkaraparpam, Dissertaion, Branch VI -Nanju Noolum Maruthuva Neethinoolum A Toxicity study on Linga Chenduram Stat Trek Random number generator Clinical management of COVID -19, Interim guidance, WHO COVID-19 pneumonia: A review of typical CT findings and differential diagnosis Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective The authors would like to thank shri. S. Ganesh IAS, Director of Indian Medicine and Homeopathy for providing the opportunity and support given for the study.