Research initiatives and network linkages in COVID-19: Neo-dynamics of R&D in the Ayush sector

Background The rapid spread and exponential increase in the mortality rate triggered the WHO to pronounce the novel coronavirus strain that caused the cases of pneumonia of unknown etiology in Hubei Province, China, in December 2019, as a Public Health Emergency of International Concern (PHEIC). The government of India had initiated various proactive steps to bolster its emergency response strategies before the disease was named a pandemic by WHO on March 11, 2020. It adopted a multipronged, pre-emptive, proactive approach in early 2020 to reduce the spread, prevent morbidity and mortality associated with COVID-19, and minimize its profound impact on the general public. Further, the state governments were tasked to invoke the Epidemic Disease Act (EDA) of 1897 to tackle the COVID-19 emergency. Various steps were taken to strengthen the healthcare infrastructure and medical care provisions. Much of the efforts were focused on strengthening the core capacities such as laboratory facilities, hospital care, ensuring availability of isolation and quarantine facilities, training for disease surveillance, supply chain, and logistics management, development of personal protection equipment, ventilators, oxygen plants, emergency care and R&D on diagnostics, vaccines, and therapy. The general public was kept at the center of the governments' containment and mitigation strategies with efforts ranging from prevention, therapeutic care, and training on COVID-19-appropriate behavior. The unavailability of standard care and insufficient access to vaccines and emergency care and an overburdened and stretched public healthcare delivery system in the low and middle-income countries (LMICs), has propelled the government to revisit conventional and traditional medicine systems to explore possible prophylactic and therapeutic measures to suitably support the health care system to provide care for the ailing public amidst the COVID-19 scenario.. As stated by Hon'ble Prime Minister in his Mann ki Baat, the world of medical science has made much progress with the help of research and innovation, and the COVID has been a time when increasing research on Ayush systems has happened, and many research studies have been published. During the initial phase of the COVID-19 pandemic, the PM had an interaction with Ayush practitioners vide video conference, wherein he expressed that Ayurveda has a long tradition of keeping the nation healthy and its importance has increased manifold in the ongoing efforts to tackle COVID-19. He urged that AYUSH scientists must come together with, ICMR, CSIR and other research organizations for evidence based research, which was taken up as a mission by the Ministry of Ayush during the COVID-19, through which many network linkages were established for planning, conduct and dissemination of the research outcomes generated among the masses. The Ministry of Ayush (MoA) also undertook several measures to contain the transmission of COVID-19, including the advisory to improve immunity and advised simple home remedies easily accessible to the general public.[1] In congruence with the guidelines on clinical management of COVID-19, the Ministry of Ayush also issued regularly updated and widely circulated various guidelines to tackle the pandemic for Ayush practitioners.[2,3] Strategies adopted for effective utilization of Ayush systems in the COVID-19 pandemic In a country such as India, where medical pluralism exists in public health care delivery, owing to its rich heritage and support for the use of traditional systems of medicine, integration of Ayush resources such as skilled workforce, infrastructure, and effective interventions intended for prophylaxis, management of COVID-19 and rehabilitation of post covid sequel, was achievable. More than eight lakh Ayush doctors, paramedical staff, and students offered their services for the clinical management, surveillance, and management of COVID isolation and quarantine centers by enlisting themselves on the COVID warrior portal.[4] Ayush healthcare personnel also obtained training at the Integrated Government Online Training (iGOT) portal. Ayush infrastructure (50000+ beds, hospitals of 750+colleges, 86 clinical facilities of National Institutes and Research Councils under the MoA) was well utilized during the pandemic crisis by converting them into quarantine centers, isolation centers, and COVID care centers (along with Ayush doctors, nurses, and other paramedical staff) by respective state Governments [Figure 1].Figure 1: Ministry of Ayush initiatives for mitigation of COVID-19Ministry of Ayush initiatives to promote awareness among the masses The Ministry has launched the 'Ayush for Immunity' campaign, a behavioral intervention program for the general public towards promoting immunity through Ayush interventions, wherein more than fifty thousand people participated during the pandemic.[5] Likewise, the Ayush COVID-19 dashboard was set up to furnish the guidelines related to Ayush measures for improving immunity, Ayush interventions for prevention and management of COVID-19, details of the research undertaken on COVID-19 through Ayush systems, official communications for the benefit of the public. Almost all the states and Union Territories, adopted several policies and practices had proactively engaged in dissemination of Ayush interventions and home remedies to the public for prophylaxis and management. The Ministry of Ayush has also launched Ayush Sanjivani app, a mobile application to record the public's patterns and trends in using Ayush preventive measures during the COVID-19 pandemic. It was also intended to motivate the users to use Ayush practices and home remedies to maintain health rather than resorting to untested and unproven remedies or self-prescription. A total of 723,459 respondents had furnished their information regarding the detailed utilization pattern, health seeking trends, and use of Ayush advocacies for prophylactic care and maintenance of health and wellbeing during the pandemic. As per the data generated from the Ayush Sanjivani App, it was observed that 85.2% of the respondents had used Ayush preventive measures for the maintenance of health, and a good proportion reported to have benefitted considerably in terms of general well-being, with a possible impact on their quality of life and specific domains of health.[6] Through the app, Ayush practitioners has also reported the acceptance, perception and utilization of Ayush advisories/measures of 1.35 Crore health seekers, during the pandemic for prophylactic purpose. Insights from the research initiatives for COVID-19 undertaken by the Ministry of Ayush Various R&D initiatives were undertaken through network linkages and collaborative research activities to harness the potential of Ayush systems to contain the impact of the COVID-19 pandemic and generate a robust evidence base for integrating and including Ayush systems in the public health architecture for infectious diseases such as COVID-19. The first step in this regard was the constitution of an Interdisciplinary Ayush R&D Task Force with scientists and experts from various domains. The task force facilitated the development of scientifically robust clinical study protocols for conducting clinical, experimental, and observational studies. There are 150 research studies comprising clinical, experimental, and epidemiological studies undertaken by the Research Councils and National Institutes under the Ministry of Ayush. These include studies on Ayurveda (75 studies), Homeopathy (30 studies), Siddha (14 studies), Unani (12 studies), and Yoga & Naturopathy (19 studies). It included 24 experimental studies, 46 prophylactic studies, 49 therapeutic (standalone and add-on treatment), 17 observational studies, ten survey studies, two studies on developing pharmacopeia standards, and two systematic reviews [Figure 2]. While the world was searching for an elusive but efficacious therapy for COVID-19, Ayush also undertook the R&D as mentioned above activities by bringing together the resources of various government agencies such as CSIR, DBT, ICMR, IIT, etc [Figure 3]. While experimental studies were intended to validate various Ayush formulations for their potential in fighting COVID-19, clinical and observational studies on the repurposed Ayush interventions were the opening salvo for the battle against time and escalating death rates.Figure 2: Ayush system-wise COVID-19 StudiesFigure 3: Major collaborators- development of a new model for research on infectious diseases through network linkagesThe clinical studies on Ayush interventions with prophylactic potential were conducted in high-risk populations either residing in containment zones or frontline workers such as those in health care or public service and demonstrated promising outcomes in reducing the incidence of COVID-19 among Ayush prophylactic care users.[7,8,9,10] The Ayush interventions showed their mettle as standalone or adjunct to the standard of care/treatment as usual in asymptomatic, mild, and moderate COVID-19. The core outcomes of these studies demonstrated early clinical recovery, achieving early negative RT-PCR assay for COVID-19, reduction in the duration of hospital stay, prevention in disease progression and complications, and improvement in quality of life with minimal AE/ADR observed [Figure 4].[11,12,13,14,15] Further, no potential interaction of Ayush interventions with conventional medicines used in routine clinical practice has been elicited clinically and also in experimental studies.Figure 4: Core Outcomes of the MoA initiatives for COVID-19MoA has also undertaken a novel research study to explore the immunomodulatory effects of Ashwagandha administration with the COVID-19 vaccine and to assess the efficacy of Ashwagandha on the sustenance of the vaccine response.[16] The outcomes of this study holds importance as sustenance of immune response to the vaccine will have implications for long-term prevention against COVID-19, including breakthrough infections. Another double-blind, randomized, placebo-controlled trial on Ashwagandha to assess its efficacy in promoting recovery in long-term symptoms following a recent COVID-19 illness has been conducted by the All India Institute of Ayurveda in collaboration with the London School of Hygiene and Tropical Medicine. Establishing inter-ministerial linkages for R&D on COVID-19 Clinical studies were undertaken on four Ayurveda interventions: Ashwagandha for prophylaxis and Yashtimadhu, Guduchi-Pippali, and AYUSH-64 (a polyherbal formulation) as an adjunct to standard of care for COVID-19 management, in collaboration with Council of Scientific & Industrial Research (CSIR). The study outcomes of the clinical study on AYUSH-64 got published in a reputed indexed medical journal.11 Based on the available therapeutic evidence, in-silico studies on AYUSH-64 and AYUSH Kwatha were also undertaken in collaboration with ICMR-National Institute of Nutrition, Hyderabad, and Indian Institute of Technology, Varanasi, respectively, to evaluate their ingredients for inhibitory action against SARS-CoV-2 Main Protease and RNA dependent RNA polymerase. Experimental studies on nine Ayush herbal extracts/formulations (Withania somnifera, Tinospora cordifolia, Glycrrhiza glabra, a combination of Tinospora cordifolia and Piper longum, AYUSH-64, Swertia chirata, Picrorrhiza kurroa, Alstonia scholaris, Ceasalpinia bonduc) and four intranasal administrations (Anu Taila, Shadbindu Taila, Sesamum oil, Cow Ghee) for assessing their therapeutic activity against SARS-CoV-2 and associated pathologies have been undertaken in collaboration with Department of Biotechnology, Govt. of India.[17] WHO-Ayush R&D Initiative A research study to assess the level of integration of Ayush systems into the public health system for combating COVID-19 was undertaken jointly by WHO-Ayush in collaboration with the Public Health Foundation of India. The findings of this study indicate that the 'National Clinical Management Protocol based on Ayurveda and Yoga for COVID-19' issued by the MoA allowed Ayush practitioners to engage alongside conventional medicine practitioners across all levels actively. It has also revealed that awareness about the different Ayush systems in society, acceptability, availability of scientific evidence regarding the safety and effectiveness of the Ayush medicines, cost-effectiveness, as well as a comprehensive approach to disease management and cultural preferences of communities, including views and past experiences of family members, were essential factors that determine the preference for and use of a particular system of medicine for ailments by the public. National Clinical Management Protocol based on Ayurveda and Yoga for COVID-19 Based on the promising outcomes of Ayush studies on COVID-19 and experimental and clinically published data indicating the potential benefits and safety of Ayush interventions, an interdisciplinary committee constituted by MoA proposed the integration of Ayurveda and Yoga interventions in the National Clinical Management Protocol for COVID-19. MoA issued the 'National Clinical Management Protocol based on Ayurveda & Yoga for COVID-19' based on recommendations of NITI Aayog and ICMR on the report of the interdisciplinary committee to enable uniform clinical management.[18] The Ayurveda protocol includes guidelines for prophylaxis against COVID-19, along with the management of asymptomatic or mild COVID-19 and the long-term effects of COVID-19, and the Yoga protocol includes measures for COVID-19 prophylaxis and post-COVID rehabilitation. Effective use of AYUSH-64 and Kabasura Kudineer for COVID-19 cases in home isolation On the evidence base generated through molecular docking, preclinical and clinical studies that favored the use of AYUSH-64 (an Ayurveda formulation) and Kabasura Kudineer (a Siddha formulation), both interventions were made available to the general public in 27 states and five union territories across India through a door to door distribution initiative in a community-based study, wherein 96139 COVID-19 patients in home isolation were dispensed with either of these interventions. The study demonstrated that people who opted to use Ayush interventions as a standalone also recovered with good clinical outcomes, comparable to those who received contemporary standard care.[19] Other R&D initiatives The Ministry of Ayush also developed an online platform for crowd-sourcing scientific evidence-based solutions from the stakeholders of Ayush systems to address the COVID-19 pandemic. The Ministry also provided technical and financial support through an extramural research scheme to undertake short-term research projects to generate evidence on the safety and efficacy of Ayush interventions for the prophylaxis and management of COVID-19. The MoA also constituted an Interdisciplinary Technical Review Committee for COVID-19 for the examination of the applications on the classical/patent and proprietary ASU&H interventions with new indication or repurposing of licensed patent and proprietary ASU&H medicines for COVID-19 in the light of quality standards, preclinical safety requirements of the drug(s), and clinical efficacy with appropriate rationale. Dissemination of research outcomes of Ayush COVID-19 studies To date, 67 manuscripts relating to the outcomes of research studies on COVID-19 have been published. Many of these scientific manuscripts are available in reputed scientific journals indexed in PubMed, Scopus, and Web of Science. Further, COVID-19-related scientific publications are also made available on the National Repository on Ayush COVID-19 Clinical and Other R&D Initiatives, which is available on the website of the Ayush Research Portal of the MoA. Lessons learned and the path forward. As stated by Hon'ble Prime Minister in one of the editions of Mann ki Bat, evidence-based research related to Yoga and Ayurveda will prove to be very significant. The Ayush systems' contribution to maintaining health and improving immunity during the COVID-19 pandemic is well accepted. Proactive initiatives taken by the MoA, inter-departmental/inter-ministerial collaboration and establishment of technical and non-technical linkages, active participation of the concerned stakeholders in successfully implementing the various initiatives, and acceptance of Ayush systems by the general public have played a significant role in successful mitigation of COVID-19 pandemic. A cohesive and coordinated approach can effectively help mainstream Ayush systems and functionally integrate the same into public health care delivery. The concerted efforts of the government, academia, administrators, scientists, and medical fraternity can usher in a new paradigm for promoting safe, informed, and effective use of Ayush interventions to optimize existing strength and augment accessibility and acceptability. Financial support and sponsorship Nil. Conflict of interest The authors declare that they have no known competing interests.