Traditional, complementary, and integrative medicine therapies for mild/moderate acute COVID-19: a systematic review and network meta-analysis.

BACKGROUND: Although the use of Traditional, Complementary, and Integrative Medicine (TCIM) interventions to treat coronavirus disease 2019 (COVID-19) is common, the effectiveness of these interventions is unclear. OBJECTIVE: To compare different TCIM interventions for the treatment of mild/moderate acute COVID-19. DATA SOURCES: EMBASE (Elsevier), Medline (OVID), VHL TCIM database, Cochrane Central, ClinicalTrials.gov, ICTRP, as of April 29th, 2025, as well as eight Chinese and four Korean databases. STUDY SELECTION: Randomized controlled trials comparing a TCIM intervention with another, the standard of care (SoC), placebo, or conventional medicine in participants with suspected, probable, or confirmed mild/moderate acute COVID-19. DATA EXTRACTION: Reviewers worked in pairs and independently extracted data and assessed the risk of bias and rated the certainty of the evidence for each outcome. RESULTS: One hundred fifty-five trials evaluating 142 TCIM therapies were eligible for review, of which 69 (45%) trials enrolling 18,627 patients met criteria for analysis, contributing at least 80 participants or 20 events to one intervention. All the following estimates come from direct evidence, as networks were sparse. Compared with SoC or placebo, high to moderate certainty evidence showed that three TCIM add-on interventions probably reduced time to symptom resolution: Lianhua Qingwen (mean difference [MD] -2.82 days, 95% confidence interval -3.14 to -2.50, high certainty); Kovir capsule (MD -3.14 days, -3.67 to -2.61, moderate certainty); and honey and Nigella sativa (MD -3.00 days, -4.12 to -1.88, moderate certainty). Using conversion to severe cases as a proxy for hospitalization, Andrographis paniculata extract probably reduced hospital admission (risk difference -15 per 1000, -24.9 to 12.3, moderate certainty) for patients at moderate risk of hospitalization. No compelling evidence supports that any TCIM intervention reduced hospital admissions for patients at low or high risk of hospitalization, or reduced mortality and mechanical ventilation requirement across all patients. High to moderate certainty evidence showed that Lianhua Qingwen, Kovir capsule, COROPROTECT kit, and Shen Cao Gan Jiang likely did not increase adverse events leading to drug discontinuation; evidence for other TCIM interventions was insufficient to inform adverse events leading to discontinuation. High to moderate certainty evidence supported that Lianhua Qingwen was effective in resolving cough (MD -1.62 days, -1.80 to -1.45, high certainty) and probably effective in resolving fatigue (MD -1.41 days, -1.73 to -1.08, moderate certainty), honey and Nigella sativa was probably effective in resolving fever (MD -4.00 days, -4.72 to -3.28, moderate certainty), and Jinghua Jiedu was probably effective in resolving cough (MD -1.72 days, -2.23 to -1.21, moderate certainty). Other TCIM interventions were either ineffective, or of uncertain effectiveness. CONCLUSION: Adding Lianhua Qingwen, Kovir capsule, or honey and Nigella sativa to SoC likely reduces symptomatic duration of mild/moderate acute COVID-19. Andrographis paniculata extract probably decreases hospital admissions among patients at moderate risk of hospitalization. Replication of positive findings is warranted. REGISTRATION: PROSPERO (CRD42024517321).