Data_Sheet_1_Flavonoids for Treating Viral Acute Respiratory Tract Infections: A Systematic Review and Meta-Analysis of 30 Randomized Controlled Trials.docx

Background: This meta-analysis aimed to investigate the efficacy and safety of flavonoids in treating viral acute respiratory tract infections (ARTIs).
Methods: Randomized controlled trials (RCTs) were entered into meta-analyses performed separately for each indication. Efficacy analyses were based on changes in disease-specific symptom scores. Safety was analyzed based on the pooled data from all eligible trials, by comparing the incidence of adverse events between flavonoids and the control.
Results: Thirty RCTs (n = 5,166) were included. In common cold, results showed that the flavonoids group decreased total cold intensity score (CIS), the sum of symptom intensity differences (SSID) of CIS, and duration of inability to work vs. the control group. In influenza, the flavonoids group improved the visual analog scores for symptoms. In coronavirus disease 2019 (COVID-19), the flavonoids group decreased the time taken for alleviation of symptoms, time taken for severe acute respiratory syndrome 2 (SARS-CoV-2) RT-PCR clearance, the RT-PCR positive subjects at day 7, time to achievement of the normal status of symptoms, patients needed oxygen, patients hospitalized and requiring mechanical ventilation, patients in ICU, days of hospitalization, patients with comorbidities, and mortality vs. the control group. In acute non-streptococcal tonsillopharyngitis, the flavonoids group decreased the TSS on day 7. In acute rhinosinusitis, the flavonoids group decreased the SSS on day 7, days off work, and duration of illness. In acute bronchitis, the flavonoids group decreased the BSS on day 7, days-off work, and duration of illness. In bronchial pneumonia, the flavonoids group decreased the time to symptoms disappearance, the level of IL- 6, IL- 8, and TNF-α. In upper respiratory tract infections, the flavonoids group decreased total CIS on day 7 and increased the improvement rate of symptoms. Furthermore, the results of the incidence of adverse reactions did not differ between the flavonoids and the control group.
Conclusion: This systematic review and meta-analysis showed that flavonoids were efficacious and safe in treating viral ARTIs including the common cold, influenza, COVID-19, acute non-streptococcal tonsillopharyngitis, acute rhinosinusitis, acute bronchitis, bronchial pneumonia, and upper respiratory tract infections. However, given the limitations, we suggest that the conclusions need to be confirmed on a larger scale with more detailed instructions in future studies.