|Year : 2022 | Volume
| Issue : 1 | Page : 31-38
A prophylactic community-based study to assess the impact of Ayuraksha kit in COVID-19: A study Protocol of a cluster randomised trial
Pallavi Suresh Mundada, Deepa Makhija, Mata Sunita, Bhogavalli Chandrasekhar Rao, Arunabh Tripathi, Kalpana Budhaji Kachre, Richa Singhal, Rakesh Kumar Rana, Adarsh Kumar, Narayanam Srikanth
Central Council for Research in Ayurvedic Sciences, New Delhi, India
|Date of Submission||29-Mar-2022|
|Date of Acceptance||05-May-2022|
|Date of Web Publication||04-Aug-2022|
Dr. Pallavi Suresh Mundada
Central Council for Resaerch in Ayurvedic Sciences, Janakpuri (Opp. D Block), New Delhi 110058
Source of Support: None, Conflict of Interest: None
BACKGROUND: The rise in the number of newly reported cases heralds the onset of the third wave of COVID-19 in India, despite the country’s relentless push for COVID-19 vaccination. In such a situation, efforts other than the vaccination, to strengthen the population’s immune system have become critical to keep the overburdened health-care system from being exhausted. Ayuraksha Kit includes four Ayurveda medicines viz., Chyawanprash, Samshamani Vati, Anu Taila and Ayush Kwath choorna. This kit is developed with an aim to enhance the general wellbeing and immunity of apparently healthy individuals. During the COVID-19 pandemic, this trial will investigate the impact of the Ayuraksha Kit as an adjunct to standard preventative measures in safeguarding people living in 12 Indian cities. MATERIALS AND METHODS: A community-based cluster randomized controlled trial will be conducted on 8316 apparently healthy adults. The clusters will be randomly allocated to two groups, intervention and control groups, in a 10:1 ratio. The advice on standard preventive measures along with masks and soaps for hand hygiene will be provided to all the study participants in both groups. Ayuraksha Kit will be given for one month to the 7560 study participants in the intervention group, and the 756 participants in the control group will be only given standard preventive measures. Effect of Ayuraksha Kit on incidence and severity of COVID-19 like symptoms and the psychological distress as an impact of risk of exposure to SARS CoV-2 will be assessed during this study. DISCUSSION AND CONCLUSION: As this study will be conducted in the areas predominantly resided by people belonging to scheduled castes in Indian cities, this cluster-RCT will determine whether the use of Ayuraksha Kit has a prophylactic potential against the incidence or on the severity of disease. TRIAL REGISTRATION: CTRI/2022/02/040156 dated 10th February 2022.
Keywords: Ayurveda, COVID-19, Prophylaxis, SARS CoV-2
|How to cite this article:|
Mundada PS, Makhija D, Sunita M, Rao BC, Tripathi A, Kachre KB, Singhal R, Rana RK, Kumar A, Srikanth N. A prophylactic community-based study to assess the impact of Ayuraksha kit in COVID-19: A study Protocol of a cluster randomised trial. J Res Ayurvedic Sci 2022;6:31-8
|How to cite this URL:|
Mundada PS, Makhija D, Sunita M, Rao BC, Tripathi A, Kachre KB, Singhal R, Rana RK, Kumar A, Srikanth N. A prophylactic community-based study to assess the impact of Ayuraksha kit in COVID-19: A study Protocol of a cluster randomised trial. J Res Ayurvedic Sci [serial online] 2022 [cited 2022 Sep 27];6:31-8. Available from: http://www.jrasccras.com/text.asp?2022/6/1/31/353411
| Background|| |
As of January 5, 2022, the total active caseload was 171,830 in India (daily positivity rate of 3.24%) with test positivity rate of 2.13% (total number of samples tested is more than 661 million). As on January 4, 2022, a total of 1892 cases of Omicron variant has been reported from 23 states (Top 5 being Maharashtra, Delhi, Kerala, Rajasthan, and Gujarat) of India. In such circumstances, several strategies, other than vaccination, to positively affect peoples health and wellbeing.
The Ministry of Ayush, Government of India, developed combinations to be dispensed in prophylactic kits to enhance the general wellbeing of apparently healthy individuals based on Ayurveda classical texts, experimental and clinical evidence, and empirical evidence from some prophylactic studies on COVID-19 that revealed the safety and efficacy of certain commonly prescribed Ayurveda medicines. One such prophylactic measure is Ayuraksha Kit which is a combination of four formulations viz., Chyawanprash, Samshamani Vati, Anu Taila (for nasal instillation) and Ayush Kwath choorna comprising powders of Tulasi (Basil)-4 part, Dalchini (Cinnamon)-2 part, Shunthi (Dry Ginger)-2 part Kalimirch (Black pepper)-1 part).
Chyawanprash is a Rasayana (rejuvenation) formulation advised to strengthen the respiratory system. The results of published clinical trials support the prophylaxis potential of Chyawanprash against COVID-19. It has been found effective and safe among high-risk participants like health care workers and other healthy individuals in reducing the incidence of COVID-19.,,
Samshamani Vati, also known as Guduchi Ghana Vati is a formulation prepared from aqueous extracts of the stem of Tinospora cordifolia. It has enhanced immunity and general well-being during the COVID-19 pandemic.,Guduchi in Ayurveda is mentioned to possess Rasayana property. An experimental study that demonstrated enhanced life span of F-1 generation of the D. melanogaster by T. cordifolia, can be interpreted as confirmation of Rasayana action of Guduchi. In a Xenotransplant model of humanized zebrafish, Guduchi Ghana Vati was reported to prevent inflammation and tissue damage induced by the production of SARS-CoV-2 spike protein. Its anti-inflammatory property is also established through experimental research.
Anu Taila is a formulation administered as Nasya (instillation of drops in the nostrils) for therapeutic as well as prophylactic purposes in different diseases related to the head, eye nose, ear and neck. According to Ayurveda concepts, instilling one to two drops of Anu Taila in both nostrils should be a part of Dinacharya (daily routine) to strengthen sensory organs, hair, teeth, facial skin and to prevent the Urdhwajatrugata Rogas (diseases of head and neck region). The prophylactic efficacy of Anu Taila was studied against the SARS CoV-2 virus in an in vivo study in the model. It was revealed that intranasal instillation of Anu Taila is useful in limiting both viral load and severity in SARS-CoV-2 infection. Herbal ingredients of Ayush Kwath are Tulsi (Ocimum sanctum), Marich (Piper nigrum), Sunthi (Zingiber officinale) and Dalchini (Cinnamonum zeylanicum) which are easily available and commonly utilized drugs at home. Based on the experimental studies conducted on these ingredients, Ayush Kwath may collectively show immune-modulatory, antiviral, anti-oxidant, anti-inflammatory, antiplatelet, anti-atherosclerotic, hepato-protective, reno-protective properties and seems to be effective in immune-regulation for controlling viral infections like COVID-19.,,,
On the basis of the rationale mentioned above, Ayuraksha Kit needs to be studied for its potential as a measure to enhance the immunity and general well-being of the people during COVID-19 pandemic. Special attention towards prophylactic care is needed for people living in crowded areas or congregate settings, where maintenance of physical distancing is difficult. Therefore, this cluster randomized study is designed to evaluate the effect of Ayuraksha kit in the prophylaxis against COVID-19.
Primary objective of this study is to assess the efficacy of Ayuraksha Kit as an add on to the standard preventive measures of COVID-19 in preventing the incidence of COVID-19 like symptoms in scheduled castes predominant areas/villages across India. Secondary objectives are as follows -
- i) To assess the efficacy of Ayuraksha Kit in preventing the incidence of RT-PCR confirmed COVID-19 cases in a subset of population randomly selected from the study population.
- ii) To assess the effect of Ayuraksha Kit on Hematological and Biochemical parameters of a subset of population randomly selected from the study population
- iii) To assess the effect of Ayuraksha Kit on severity of upper respiratory symptoms if developed during the study period
- iv) To assess the effect of Ayuraksha Kit on the clinical outcome of the participants developing COVID-19 like symptoms or COVID-19 illness diagnosed by RT-PCR, during the study period.
- v) To assess the effect of Ayuraksha Kit on the psychological distress as an impact of COVID-19 exposure, among the study population
- vi) To compare the incidence of adverse events (if any) among the study groups.
This is an open label, multi-centre, prospective, interventional, randomized controlled Community based study.
The study will be conducted in 12 cities of India viz., New Delhi, Cheruthuruthy, Bhubaneshwar, Mumbai, Jaipur, Vijaywada, Nagpur, Trivandrum, Guwahati, Ahmedabad, Bangalore and Chennai through the Ayurveda research institutes situated in the respective cities. Out of these 12 centers, at 4 study centers, a subset of the population will be studied in detail by conducting laboratory testing. The participants of this subset will be informed about the study procedure and written or electronically generated consent will be obtained from the study participants.
Participants aged 18 to 70 years old, of any sex, from the listed scheduled castes predominant areas/villages across India who did not have COVID-19-like symptoms and willing to provide informed consent will be included in this study. Participants who have been vaccinated or are taking any other prophylactic medicine other than Ayuraksha kit for COVID -19 will also be included in the study.
Participants presenting with COVID-19 like symptoms or those who are diagnosed with COVID-19 by positive RT-PCR test within one month prior to inclusion or those having history of uncontrolled diabetes mellitus or uncontrolled hypertension or those having any disease condition that would require immediate medical or surgical intervention or those who are known case of immune-compromised states like HIV or COPD, tuberculosis, cancer, hepatitis or those on steroids or any immunosuppressive therapy will be excluded. Participants who have already participated in any other clinical trial within one month prior to screening or those having a history of allergy to any medicine that is part of the Ayuraksha Kit will be excluded. Pregnant, lactating women or women planning for pregnancy and the asymptomatic RT-PCR confirmed COVID-19 cases at the time of screening would also be excluded.
Period of intervention will be 30 days from the Day of enrolment.
Group-I (Intervention group)
Participants in this group will receive Ayuraksha Kit as an add-on to the standard preventive measures for COVID-19. Instructions to follow hand hygiene and respiratory etiquettes; soap for hand wash and masks will be provided to all the participants. The components of the Ayuraksha Kit are Chyawanprash (180 gm), Ayush kwath choorna (100 gm), Samshamani Vati (120 tablets each of 250 mg) and Anu Taila (20 ml). The Ayuraksha Kit will be procured from a GMP-certified Ayurveda drug manufacturer. To prepare decoction from Ayush kwath choorna,the participants will be instructed to boil 3gm of Ayush Kwath powder in 150 ml (about a cup) potable water until it reduces to half, i.e., 75 ml to be consumed once daily. For palatability, jaggery or raisins can be added if needed. The dose of Chyawanprash, Ayush kwath choorna and Samshamani Vati will be 6 gm OD in the morning, 3 gm (boiled in 150 ml of water filtered and consume like tea) once a day and two tablets twice a day with normal water respectively. Anu Taila is to be instilled in the dose of two drops in each nostril once daily.
Group-II (Control arm)
Participants in this group will receive standard preventive measures for COVID-19. Instructions to follow hand hygiene and respiratory etiquettes; soap for hand wash and masks will be provided to all the participants. Standard preventive measures will be advised as per guidelines issued by the Ministry of Health and Family Welfare, Government of India.
If any participant develops any serious adverse event during the study period then he/she will be withdrawn from the study. Such participants will be given appropriate treatment as per the clinical presentation and their recovery will be followed. Similarly if the study participants developed any Treatment Emergent Adverse Events (TEAE), then they will also be withdrawn from the study. The cases (if any) of TEAE will be given appropriate incidental care through Ayurveda or referred to a higher medical facility. The participants not adhering to the study protocol or not willing to continue their participation will be allowed to withdraw from the study.
The data of all the participants who withdraw from the study will be recorded. The investigators will make effort to maintain contact with the withdrawal participants at least until the conclusion of the research period to keep track of any adverse events or clinical manifestations. Within two working days, the sponsor and the Ethics Committee will be notified of the decision to withdraw a participant from the trial, and thorough justification.
The primary outcome measures include comparing the proportion of participants developing COVID-19 like symptoms in both the groups during the study period. [Number of participants with fever, cough, or other respiratory/systemic symptoms (including but not limited to fatigue, myalgias, arthralgias, shortness of breath, sore throat, headache, chills, coryza, nausea, vomiting, diarrhoea)].
- 1) Comparison of incidence of RT-PCR diagnosed cases of COVID-19 in both the groups in a subset of the population randomly selected from the study population will be done at the time of screening and as and when participants report the incidence of symptoms or on 30th Day if they remain asymptomatic through-out the study period.
- 2) Any change in CBC (Hemoglobin, RBC count, TLC, DLC, Platelet count and Hematocrit), LFT (AST, ALT, ALP, Serum Bilirubin, Serum Albumin and Serum Globulin) and RFT (Serum Creatinine, Blood Urea, Serum Uric Acid, eGFR) from baseline at the end of study period in a subset of population randomly selected from the study population.
- 3) Comparison of the severity of Respiratory symptoms if developed in both the groups through the Wisconsin Upper Respiratory Symptoms Survey (WURSS-24) questionnaire. [Time frame: Daily- As soon as the participant reports of being symptomatic till they become asymptomatic or till 07 days whichever earlier.]
- 4) Comparison of the clinical outcome of the participants developing COVID-19-like symptoms in both the groups, as per the WHO clinical progression scale (10 point).
- 5) Any change in psychological distress as an impact of exposure to COVID-19 among participants of both the groups will be assessed by using Kessler Psychological Distress Scale (K10). [Time frame: Baseline and at day 30]
- 6) Percentage of drug compliance
- 7) The proportion of participants exhibiting adverse events of any grade at day 15 and 30 in both the groups.
- 8) Occurrence of TEAE.
The time schedule of enrolment, interventions, assessments, and follow-up visits for participants is in [Table 1].
Assuming the anticipated incidence rate of COVID-19 (flu-like symptoms) in the control group as 6.5% and in the intervention group as 3.0% at 95% confidence and 80% power, the sample size for control group was calculated as 275 and for intervention group as 2750. As the above study will be conducted at 12 centers through cluster sampling, at each center to adjust the effect of cluster sampling, the design effect of 2.725 was considered in sample size increment [based on the cluster size of 70 (including drop out) and Intra cluster coefficient =0.025.] The required sample size for intervention group was calculated as 7494 (approximate 625 at each centre), and for control group as 750 (approximate 63 at each centre). The total sample size for study is 8316 (7560 + 756).
After receiving approval from the Institutional Ethics Committee (IEC) and registering the study with CTRI, the residents of the identified areas/villages will be informed about the study in detail (in their regional language) through banners and Information Education Communication materials. During door-to-door survey, apparently healthy participants from the study areas will be asked for providing their consent electronically or in writing regarding their participation in the study (Patient information sheet and consent form attached as supplementary file). Participants will be recruited in the study based on the defined inclusion and exclusion criteria. Participant allocation in either study groups shall be based on a cluster randomization schedule.
Cluster randomization will be done for sampling of population in ratio of 10:1 in the intervention arm (Ayuraksha Kit as add on to the standard preventive measures of COVID-19) and control arm (standard preventive measures of COVID-19) respectively. Each study center will identify twenty areas predominantly inhabited by people belonging to scheduled castes. A list of such villages/areas and approximate population residing there will be prepared for cluster randomization. The randomization process will be done centrally by the biostatistician. The list of randomly selected 10 clusters will be conveyed to the study centres for execution of the study. (10 clusters in the intervention group and 1 in the control group).
The allocation concealment will not be done as the participants will be recruited from the field through a door-to-door survey by the study personnel in the clusters randomly selected initially.
Blinding will not be done except that the laboratory personnel will not be made aware of the allocation of the participants to either group. The study is of open-label design.
Data collection methods
Demographic data, clinical history, details of COVID-19 vaccination and concomitant medications, and score of Immune status [through Immune Status Questionnaire] of the enrolled participants will be recorded at the baseline in the case record form (CRF). All the participants will be motivated to follow the standard preventive measures as per the guidelines of Central/State/local health authorities to prevent the spread of COVID-19. The investigator's contact number and address of the study center will be provided to all the participants at the time of enrolment. Drug compliance will be assessed by counting the number of days of medicine intake in the prescribed dosage. During telephonic follow-ups, the participants of both groups will be motivated to comply with the standard preventive measures. The details about vaccination and other prophylactic measures used will be noted, and the results will be analyzed accordingly. A gap of one week between vaccination and enrollment will be maintained.
All the participants will be instructed to inform about any adverse event if happens during the study period. The participants will be instructed to immediately inform the investigator if they develop any signs and symptoms compatible with COVID-19 [fever, cough, or other respiratory/systemic symptoms (including but not limited to fatigue, myalgias, arthralgias, shortness of breath, sore throat, headache, chills, coryza, nausea, vomiting, diarrhoea)]. For severity assessment of upper respiratory symptoms, the WURSS-24 tool will be filled daily by the study personnel through telephonic follow-up of such participants till they become asymptomatic or until 7 days (whichever is earlier). The participants may be encouraged for RT-PCR testing if required.
At 04 study centers, a subset of the population will be studied for incidence of RT-PCR confirmed COVID-19. At each of the 04 study centres, 140 participants from the randomly selected 02 clusters allocated to the intervention group and 14 participants from the cluster allocated to the control group will undergo the following tests –
- 1) RT-PCR assay for COVID-19, Complete Blood Count (CBC), Liver Function Test (LFT) and Renal Function Test (RFT), at the time of screening
- 2) RT-PCR assay for COVID-19 of symptomatic cases during the study period, as soon as the patient reports symptoms compatible with COVID-19 illness.*
- 3) RT-PCR assay for COVID-19 of the participants not presenting with any symptoms throughout the study period, at the end of the study period.**
- 4) CBC, LFT, and RFT of all the participants at the end of the study period.*
- *If the participant is tested positive for RT-PCR, they will be withdrawn from the study but such participants will be observed to record the clinical progression and appropriate guidance and referral shall be provided to them by the investigators. If the participant is tested negative for RT-PCR or is not willing for RT-PCR, the intervention will be continued. Such participants will be observed for their clinical progression of the illness and if the score of clinical progression of COVID-19 as per WHO guidelines is four or above, the patient will be referred to a higher centre for management.
- **If the participant is tested positive for RT-PCR at the end of the study, they will be given appropriate advice regarding isolation and further management.
All participants will be followed up telephonically on the 15th Day and 30th Days, and the data will be collected in the CRF. During follow-ups, the occurrence of any symptom and need for any rescue medication will be recorded. The psychological impact of exposure to COVID-19 will be assessed through Kessler Psychological Distress Scale (K10) at baseline and day 30.
Reporting the data of each subject to the monitoring center and notifying the ADR/AE, if any
Description of the adverse events that occurred in the last two weeks will be asked orally through telephone and will be noted in the CRF. Assessment of seriousness and causality of the adverse event will be done and documented clearly in the adverse event module of the CRF. Appropriate and timely management of suspected adverse drug reactions through Ayurveda management or referral to higher medical facility. The Investigators will report all the serious adverse events and treatment-emergent adverse events to the Ethics committee and the central monitoring unit at the earliest. The clinical course of each event will be followed until resolution, stabilization, or until it has been determined that the study treatment or participation is not the cause if any adverse event that is ongoing at the end of the study will be followed up for that respective event to determine the outcome.
A committee consisting of selected members would be appointed by CCRAS for monitoring of data.
The collected data on quantitative variables will be tested for normality. Quantitative data will be described in mean (SD) or median (min, max) as per their distribution. Qualitative data will be presented in Number (%). Quantitative variables will be analyzed using paired sample t-test/ Wilcoxon Sign rank test for observing within group differences. Unpaired sample t-test/Mann-Whitney test will be used for comparing the differences between two groups. Qualitative data will be compared using chi-square/fisher exact test between two groups. McNemar chi-square test will be used for within group comparison of qualitative data. Multivariable regression analysis will be performed to remove the effect of confounding variable if it is necessary. The level of significance will be considered at 5%. Stata 16.1 software will be used for analysis.
All the protocol amendments and their justification will be reported to the ethics committee and the sponsors at the earliest.
All study-related information will be stored securely at the study site. All participant information will be stored in locked file cabinets in areas with limited access. All the data collected in CRF will be entered in an e-format developed by the funding agency. All records that contain names or other personal identifiers, such as locator forms and informed consent forms, will be stored separately from study records identified by code number. All local databases will be secured with password-protected access systems. Forms, lists, logbooks, appointment books, and listings that link participant ID numbers to other identifying information will be stored in a separate, locked file in an area with limited access. The data will be identified by a coded identification number only to maintain participant confidentiality.
| Discussion|| |
This study is a community based cluster randomized controlled trial. It may scientifically evaluate the effect of Ayuraksha Kit, as prophylactic intervention for COVID-19 in the community setting. Ayuraksha kit has already been advocated through the guidelines issued by the government however, no report regarding its efficacy and safety is available in the public domain till date. So this study may be useful in testing the hypothesis of the prophylactic efficacy of Ayuraksha Kit against COVID-19.
Ayuraksha Kit contains the formulations that are effective in treating the upper respiratory symptoms and mild fever as per classical texts. Although Ayush Kwath (one of the ingredients of the Ayuraksha Kit) is not a classical Ayurveda formulation, it contains powder of herbs known to improve upper respiratory symptoms when taken as a home remedy for symptomatic relief. In this clinical study, outcome of the participants showing COVID-19 like symptoms will be observed in detail so that, the role of Ayuraksha Kit can be explored before infection and during the non-severe stage in preventing propagation of the pathogen to lower airways and thus help in early recovery from mild symptoms. This cluster-RCT may determine whether the use of Ayurveda Raksha Kit has a prophylactic potential against the incidence or on the severity of disease. Moreover, if proven effective, the Ayuraksha Kit may also be studied for its prophylactic effect in other flu-like illnesses with symptoms similar to mild COVID-19.
Access to data
The funding agency will have access to the complete data.
Ancillary and Post-trial care
No ancillary studies are proposed with this trial. After completion of study period, the participants will be given routine Ayurveda medical care if required.
Role of Study Sponsor
The sponsor has designed this study and will analyse the data and publish the results. However, it is not involved in the manufacturing and commercialization of the trial drugs as all the drugs are classical/non-patented Ayurveda medicines.
Registration of the study
The study has been registered prospectively in Clinical Trial Registry of India vide CTRI/2022/02/040156 on February 10, 2022.
Ethics approval and consent to participate
The study has been approved by the Institutional Ethics committees of all the 12 study centres viz., ARARI, Chennai; CARI, Bangalore; CARI, Guwahati; CARI Mumbai; CARI, New Delhi; CARI, Bhubaneshwar; NARIP, Cheruthuruthy; RARI, Ahmedabad; RARI, Trivandrum; RARI, Nagpur; RARI, Jaipur and RARI, Vijayawada.
The eligible participants will be enrolled in the study only after obtaining their informed consent.
Financial support and sponsorship
Central Council for Research in Ayurvedic Sciences, under Ministry of Ayush, Government of India, New Delhi has funded this study. This protocol was developed by CCRAS. The protocol was peer reviewed by the concerned subject experts before approval of grant to the investigators .
The protocol was developed as per SPIRIT guidelines and the SPIRIT checklist has been attached as supplementary file. DM conceived the study. PM and SM initiated the study design. Protocol was finalized with inputs from DM, BCSR, AK and NS. RR, RS and AT provided the statistical inputs. The manuscript was drafted by PM and KK. All authors contributed to refinement of the study protocol. All the authors have read and approved the final draft of the manuscript.
Conflicts of interest
The authors declare no competing interests. The authors are employees of Central Council for Research in Ayurvedic Sciences (CCRAS), a research organisation under Government of India.
The authors acknowledge the contribution of the study investigators at all the study centres while finalizing the protocol. We thank the senior research fellows Dr. Akanksha, Dr. Gatha and Dr. Devayani for their technical assistance in drafting the protocol. We also thank Mrs. Deepika, Ms. Shaheen and Ms. Nisha for their efforts in co-ordinating with all the study centres. The authors acknowledge the pharmacy (IMPCL, Almorha, Uttarakhand) for timely provision of the study drugs.
Protocol version: CCRAS-IMR-ARKSCSP:1.1 dated 28th January 2022
| Supplementary file|| |
SPIRIT checklist, Informed Consent Form and Patient Information Sheet, Case Report Form.
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