AYUSH (Indian System of Medicines) Therapeutics for COVID-19: A Living Systematic Review and Meta-Analysis (First Update)

Background: In India, alternative and complementary therapies (Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy [AYUSH] medicines) are extensively utilized in COVID-19 management, and some were investigated clinically. This study assessed the effectiveness of AYUSH therapeutic on COVID-19 through a living systematic review and meta-analysis approach. Methods: Databases like PubMed; the Cochrane central register of controlled trials; WHO COVID-19 database; the central trial registry-India; Digital Helpline for Ayurveda Research Articles and AYUSH research portal, and preprint repositories were searched till August 1, 2021. Randomized controlled trials or analytical observational studies were included only. Primary outcomes selected were clinical improvement, WHO ordinal scale, viral clearance, and mortality, whereas secondary outcomes were the use of O2 therapy or mechanical ventilator, admission to high dependency unit or emergency unit, duration of hospitalization, the time to symptom resolution, and adverse events. The risk of bias was evaluated by Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB-2) and Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) tools; data were synthesized through RevMan 5.4 tool, and the certainty of the evidence was ranked through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Of 3609 studies retrieved, 17 were included in the systematic review, and 3 AYUSH therapeutics were meta-analyzed. Meta-analysis suggested that add-on AYUSH-64 likely provides therapeutic benefits by reducing time to symptom resolution (mean difference [MD] 2.35 days lower [95% confidence interval, CI; 4.05 lower to 0.65 lower]) and hastening clinical improvement (365 more per 1000 [95% CI; 4 more to 1000 more]) in mild-to-moderate COVID-19 patients. Kabasura Kudineer adjuvant to standard care is likely to reduce symptom resolution (MD; 1.93 days lower [95% CI; 2.28 lower to 1.58 lower]) and hospital stay (MD; 4.2 days lower [95% CI; 4.97 lower to 3.43 lower]) in mild-to-moderate COVID-19 patients. Co-administration of Guduchi (Tinospora cordifolia [Willd.] Miers.) to standard care may reduce the duration of hospitalization (MD; 3.93 days, lower [95% CI; 8.83 lower to 0.97 higher]) in mild-to-moderate COVID-19 patients. Furthermore, all three agents seemed safe in adjunct usage to standard care. The certainty of evidence for most outcomes was moderate to low, primarily due to the high risk of bias or imprecision owing to the small sample size. Conclusion: Rational use of integrated or standalone AYUSH interventions in mild-to-moderate COVID-19 patients is safe and may provide therapeutic benefits. The effect estimates may be changed with additional evidence in upcoming updates.