CoVAM: Complementary and Alternative Medicine Clinical Trials Database for COVID-19 Disease

Since the inception of the COVID-19 pandemic, a large number of clinical trials on complementary and alternative medicine (CAM) for SARS-CoV-2 infection (COVID-19 disease) have been registered. The information is scattered at different resources making it dicult for researchers, scientists, health care professionals, and the general public to remain up-to-date on the latest CAM clinical trials being registered for COVID-19. The Complementary and Alternative Medicine Clinical Trials Database CoVAM (http://www.covam.in) is developed to provide the scientic community easy access to the latest information on the CAM clinical trials registered globally for COVID-19 disease. To develop the CoVAM, MySQL was used. API management was done through NodeJs (With Express), and Angular 11 was used as front end. The CoVAM is a single platform organized by ten CAM subtypes such as Acupuncture, Auricular point pressing, Ayurveda, Chiropractic, Homeopathy, Psychotherapy, Siddha, Traditional Chinese Medicine (TCM), Vitamins and dietary supplements, and Yoga/ Exercise. Each subtype has information on CAM medicines/ therapy being registered, the full title of the clinical trial, sponsor name, sponsor protocol number/ ID, age of the population, study type, actual number of participant enrolment for the trial, followed by the start date, phase, and status of the clinical trial. Each fact is linked to the clinical trial database/s from where the information was procured. Additionally, CoVAM is hyperlinked with PubMed for providing recent updates on COVID-19 and CAM research. To the best of our knowledge, CoVAM is a rst-of-its-kind database that provides comprehensive information on globally registered CAMs related clinical trials conducted on COVID-19 disease.


Introduction
COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2 with clinical manifestations such as dry cough, sore throat, fever, body ache, di culty in breathing, etc. [1]. Globally, there have been 156,496,592 con rmed cases and 3,264,143 COVID-19 related deaths as per WHO until 8 th May 2021 [2].
The rst generation of vaccines has been approved for emergency use by drug regulatory authorities of different nations [3]. However, they are not advised to people with allergies, autoimmune disorders, suppressed immune systems, breastfeeding or pregnant mothers and children below the age of sixteen, which covers a large segment of the global population [4]. Since the inception of the COVID-19 disease, public health practitioners are promoting and trying to nd the solution for the management of COVID-19 disease through complementary and alternative medicine (CAM; diagnostic and therapeutic disciplines used along with conventional medicine) [5,6]. In China itself, the total number of con rmed cases treated by Traditional Chinese Medicine (TCM) has reached 60,107 [7]. An Ayurvedic (Traditional Indian System of Medicine) drug 'Coronil' has got certi cation from AYUSH (Ayurveda, Yoga, and Naturopathy, Unani, Siddha, and Homeopathy) Ministry in India as a drug that can be used as a supporting measure in COVID-19 disease [8][9][10]. Another drug AAYUDH Advance is also announced as a clinically tested medicine for COVID-19 management and treatment [11]. Since the beginning of the SARS-CoV-2 outspread to the world, researchers and clinicians have started clinical trials on CAMs, and registered their studies at various clinical trial databases of the world. To the best of our knowledge, there is only one database available on TCM clinical trials on COVID-19, however, an all-inclusive database on different CAM subtypes is still unavailable [12]. Sieving out information pertaining to CAM from multiple clinical trial-related databases can prove to be a cumbersome and time taking process. In order to make the process of extracting information related to CAM straightforward, a comprehensive and user-friendly database "CoVAM" (COVID-19 Alternative Medicine Clinical Trials Database) was developed. It provides the scienti c community with the information of CAM clinical trials on SARS-CoV-2 at a single platform, thereby making the process of searching user-friendly and time-saving, preventing the knowledge obtained from these clinical trials from getting lost in the vast ocean of COVID-19 clinical trials.

Materials And Methods
Records on COVID-19 and CAM comprising Acupuncture, Auricular point pressing, Ayurveda, Chiropractic, Homeopathy, Psychotherapy, Siddha, TCM, Yoga and exercise, and Vitamins & dietary supplements were systematically collected, ltered, and compiled using a query set of keywords/synonyms till 26 th March Table S1). Brie y, the screening of records was performed on 15 different clinical trial databases from where the records on COVID-19 clinical trials and CAM were included. In addition, freewheeling searches of the health ministry and government websites of different countries were also performed to retrieve all the relevant records on registered CAM-related COVID-19 clinical trials (Table 1). If the same medicines/therapy were registered at two or more databases then they were clubbed as one entry represented by all databases links. However, if the title, sponsor protocol number/ ID, study type, number of enrolments, the start date of the clinical trial, phase, or status of clinical trial varies then they were

Results
A total of 292 clinical trials on CAM were obtained after the screening of records using a set of keywords/synonyms (Supplementary Table S1). For easy access and option for periodic update of information, the database CoVAM was developed using MySQL. API management was done through NodeJs (With Express), and Angular 11 was used as front end.

CoVAM database features
It provides end-user the facility to view and navigate through different CAM topics. While going through a speci c CAM subtype such as Ayurveda, Auricular point pressing, etc, the end-user can search all entries/data or can rapidly perform a selective search by selecting a particular heading from the drop-down menu above the search bar and typing the relevant search term in the 'search box'. The CoVAM also gives the featured information of COVID-19 clinical trial statistics, and ongoing research on COVID-19 and CAM via hyperlinking to PubMed [13,14]. The primary functions are summarized in Figure 1.

Discussion
The CoVAM database gives comprehensive and all-encompassing information about the CAM-related clinical trials on COVID-19 disease. For updated research publications on CAM and SARS-CoV-2, the database is hyperlinked to PubMed. Our database would be useful for scientists, healthcare personnel, and the common man involved with nding the solutions for the management of COVID-19 disease. The 1 st version of CoVAM includes >250 COVID-19 related clinical trials on our CAM database, however, we are still working and will periodically update the entries of trials which will be re ected on the CoVAM 'Latest News' section.
We included ten CAM subtypes i.e. Acupuncture, Auricular point pressing, Ayurveda, Chiropractic, Homeopathy, Psychotherapy, Siddha, TCM, Yoga and exercise, and Vitamins & dietary supplements, for this release but will expand our horizon to ensure that the users get the latest and updated information on COVID-19 related clinical trials on CAM. There is a duplication of 14 clinical trial records which we have uploaded as separate entries, as they have different registration dates at different databases {particularly the Chinese Clinical Trial Register (ChiCTR) and ClinicalTrials (NCT) trials registered at Global Clinical Trials Data (GCT) database}; therefore, records should be interpreted with caution. Although, along with freewheeling search, 15 databases were referred there is a great possibility that few clinical trials or databases might have not been covered. Hence, we appreciate and look forward to end-user feedback to guide us for further enhancements.

Conclusion
Scientists and health care personnel are seeking alternative options to manage vulnerable groups for whom the COVID-19 vaccines are not advised. CoVAM will help in providing factual information regarding ongoing clinical trials on CAM under one roof without having to perform the cumbersome task of sieving out information through various public search web engines. Hence, it will help health care professionals by letting them keep tabs on ongoing trials in different elds of CAM thereby, aiding them in the treatment that they can provide to improve a patient's method of care. The database has been made keeping in mind the needs of the society and the fact that with each other's support we may exterminate COVID-19.

Declarations Data Availability
CoVAM is free and open to all users and there is no login requirement. CoVAM can be accessed via http://www.covam.in

Funding
The work is done for humanity by the members of the non-pro table charitable trust (Society for Life Sciences and Human Health, 84/8, K, Allahpur, Prayagraj, U.P, India) and is not supported by any funding organization.

Con icts of interest
None declared.
Authors' contributions VS and AS conceived and designed the project. ZM, AS, and VS performed the screening. AN, and AV worked on the designs. AS developed the database. VS, AS, ZM, and AN wrote the rst draft of the manuscript. AN, VS, RS and PR reviewed and wrote the nal version of the manuscript. Table   Table 1 Databases screened and their respective links