Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

Corrigendum: Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

[This corrects the article DOI: 10.3389/fmed.2022.761655.].

Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

INTRODUCTION: Vaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD™) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination. METHODS AND ANALYSIS: We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks. ETHICS AND DISSEMINATION: Ethics approval was obtained through the Central and Institutional Ethics Committees. Participant recruitment commenced in December 2021. Results will be presented in conferences and published in preprints followed by peer-reviewed medical journals. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [CTRI/2021/06/034496].

Research, biomedicine and Ayurveda: From evidence-based medicine to evidence-informed healthcare.

As the search for effective treatment for Covid-19 intensifies, traditional medicine systems are receiving increasing attention from researchers as well as the public. While scientific rigour is non-negotiable, there remain fundamental issues to be addressed when bringing evidence from traditional systems. Here we examine some of these issues pertaining to Ayurveda and the underlying philosophical underpinnings, and suggest potential ways to move forward. We find an ability to emerge from the cage of "biomedicalism" and its foundational reductionism essential for appropriate research in Ayurveda. We caution against pursuing research in Ayurveda by just mimicking modern medicine and highlight the need for appropriate use of modern science tools and methods to understand Ayurveda and explore its potential for healthcare. We emphasise the need and potential for transdisciplinary research in Ayurveda. A balance between evidence-based medicine and evidence-informed healthcare is required.

Ayurveda botanicals in COVID-19 management: An in silico multi-target approach.

The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagious disease. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific antivirals and immunomodulators. Ayurvedic Rasayana therapy has been traditionally used in India for its immunomodulatory and adaptogenic effects, and more recently has been included as therapeutic adjuvant for several maladies. Amongst several others, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) play an important role in Rasayana therapy. The objective of this study was to explore the immunomodulatory and anti SARS-CoV2 potential of phytoconstituents from Ashwagandha, Guduchi and Shatavari using network pharmacology and docking. The plant extracts were prepared as per ayurvedic procedures and a total of 31 phytoconstituents were identified using UHPLC-PDA and mass spectrometry studies. To assess the immunomodulatory potential of these phytoconstituents an in-silico network pharmacology model was constructed. The model predicts that the phytoconstituents possess the potential to modulate several targets in immune pathways potentially providing a protective role. To explore if these phytoconstituents also possess antiviral activity, docking was performed with the Spike protein, Main Protease and RNA dependent RNA polymerase of the virus. Interestingly, several phytoconstituents are predicted to possess good affinity for the three targets, suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would not be adverse herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals as therapeutic adjuvants in the management of COVID-19 following rigorous experimental validation.

Withania somnifera (L.) Dunal: Opportunity for Clinical Repurposing in COVID-19 Management.

As the COVID-19 pandemic is progressing, the therapeutic gaps in conventional management have highlighted the need for the integration of traditional knowledge systems with modern medicine. Ayurvedic medicines, especially Ashwagandha (Withania somnifera (L.) Dunal, WS), may be beneficial in the management of COVID-19. WS is a widely prescribed Ayurvedic botanical known as an immunomodulatory, antiviral, anti-inflammatory, and adaptogenic agent. The chemical profile and pharmacological activities of WS have been extensively reported. Several clinical studies have reported its safety for use in humans. This review presents a research synthesis of in silico, in vitro, in vivo, and clinical studies on Withania somnifera (L.) Dunal (WS) and discusses its potential for prophylaxis and management of COVID-19. We have collated the data from studies on WS that focused on viral infections (HIV, HSV, H1N1 influenza, etc.) and noncommunicable diseases (hypertension, diabetes, cancer, etc.). The experimental literature indicates that WS has the potential for 1) maintaining immune homeostasis, 2) regulating inflammation, 3) suppressing pro-inflammatory cytokines, 4) organ protection (nervous system, heart, lung, liver, and kidney), and 5) anti-stress, antihypertensive, and antidiabetic activities. Using these trends, the review presents a triangulation of Ayurveda wisdom, pharmacological properties, and COVID-19 pathophysiology ranging from viral entry to end-stage acute respiratory distress syndrome (ARDS). The review proposes WS as a potential therapeutic adjuvant for various stages of COVID-19 management. WS may also have beneficial effects on comorbidities associated with the COVID-19. However, systematic studies are needed to realize the potential of WS for improving clinical outcome of patients with COVID-19.

AYUSH, modern medicine and the Covid-19 pandemic.

The COVID-19 pandemic has posed several challenges to the Indian healthcare system. Here, we examine the situation in India considering the moral and ethical imperatives of decision making for public health. Currently, in the absence of proven therapies, empirical evidence is being used for treatment of Covid-19 disease. We find a dual standard of practice. Currently, only modern medicine therapies are used on an empirical basis, however, the same principle is not considered for the use of AYUSH systems. Appropriate use of evidence is required. In the ethics context and in the interest of the larger public good, we suggest the inclusion of simple and safe measures from AYUSH systems in the integrative protocols for prophylaxis and treatment of Covid-19. Keywords: AYUSH systems, Covid-19, pandemic, prophylaxis, evidence, empirical evidence, priority setting, public health decision making, global health emergencies,complementary medicine, integrative healthcare.