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

  • 2022-02-16
  • Frontiers in public health 10
    • Jia Yao
    • Yuan Zhang
    • Xian-Zhe Wang
    • Jia Zhao
    • Zhao-Jun Yang
    • Yu-Ping Lin
    • Lu Sun
    • Qi-Yun Lu
    • Guan-Jie Fan

Study Design

Type
Meta-Analysis
Population
patients with viral acute respiratory tract infections (ARTIs)
Methods
Meta-analysis of randomized controlled trials, efficacy based on symptom scores, safety based on adverse events incidence

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

In this study, 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 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 COVID-19, the flavonoids group decreased the time taken for alleviation of symptoms, time taken for 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, and mortality vs. the control group. In acute non-streptococcal tonsillopharyngitis, the flavonoids group decreased the tonsillitis severity score (TSS) on day 7. In acute rhinosinusitis, the flavonoids group decreased the sinusitis severity score (SSS) on day 7, days off work, and duration of illness. In acute bronchitis, the flavonoids group decreased the bronchitis severity score (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 interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (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

Results from this systematic review and meta-analysis suggested 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, uncertainty remains because there were few RCTs per type of ARTI and many of the RCTs were small and of low quality with a substantial risk of bias. Given the limitations, we suggest that the conclusions need to be confirmed on a larger scale with more detailed instructions in future studies.Systematic Review Registration: inplasy.com/inplasy-2021-8-0107/, identifier: INPLASY20218010.

Research Insights

  • Red Grape→Improved Symptom Improvement Rate

    In upper respiratory tract infections, the flavonoids group decreased total CIS on day 7 and increased the improvement rate of symptoms.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Improved Symptom Severity

    In influenza, the flavonoids group improved the visual analog scores for symptoms.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Increased Interleukin 8 Levels

    interleukin-8 (IL-8)

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Increased Symptom Improvement Rate

    In upper respiratory tract infections, the flavonoids group decreased total CIS on day 7 and increased the improvement rate of symptoms.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Bronchitis Severity Score

    In acute bronchitis, the flavonoids group decreased the bronchitis severity score (BSS) on day 7, days off work, and duration of illness.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Cold Intensity Score

    In upper respiratory tract infections, the flavonoids group decreased total CIS on day 7 and increased the improvement rate of symptoms.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Days Off Work

    In acute bronchitis, the flavonoids group decreased the bronchitis severity score (BSS) on day 7, days off work, and duration of illness.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Hospitalization Duration

    days of hospitalization

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced ICU Admission

    patients in ICU

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Illness Duration

    In acute bronchitis, the flavonoids group decreased the bronchitis severity score (BSS) on day 7, days off work, and duration of illness.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Interleukin-6 Levels

    the level of interleukin-6 (IL-6)

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Mortality Risk

    mortality

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Need for Mechanical Ventilation

    patients hospitalized and requiring mechanical ventilation

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Need for Oxygen Therapy

    patients needed oxygen

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced RT-PCR Positivity

    the RT-PCR positive subjects at day 7

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Sinusitis Severity Score

    In acute rhinosinusitis, the flavonoids group decreased the sinusitis severity score (SSS) on day 7, days off work, and duration of illness.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Symptom Duration

    In bronchial pneumonia, the flavonoids group decreased the time to symptoms disappearance, the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α).

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Symptom Intensity

    In common cold, results showed that the flavonoids group decreased total cold intensity score (CIS), the sum of sum of symptom intensity differences (SSID) of CIS, and duration of inability to work vs. the control group.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Symptom Severity

    In influenza, the flavonoids group improved the visual analog scores for symptoms.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Time to Normal Symptom Status

    time to achievement of the normal status of symptoms

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Time to Symptom Alleviation

    In COVID-19, the flavonoids group decreased the time taken for alleviation of symptoms, time taken for 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, and mortality vs. the control group.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Time to Symptom Disappearance

    In bronchial pneumonia, the flavonoids group decreased the time to symptoms disappearance, the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α).

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Time to Viral Clearance

    In COVID-19, the flavonoids group decreased the time taken for alleviation of symptoms, time taken for 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, and mortality vs. the control group.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Tonsillitis Severity

    In acute non-streptococcal tonsillopharyngitis, the flavonoids group decreased the tonsillitis severity score (TSS) on day 7.

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Tumor Necrosis Factor Alpha

    tumor necrosis factor-α (TNF-α)

    Effect
    Beneficial
    Effect size
    Small
  • Red Grape→Reduced Work Disability Duration

    In common cold, results showed that the flavonoids group decreased total cold intensity score (CIS), the sum of sum of symptom intensity differences (SSID) of CIS, and duration of inability to work vs. the control group.

    Effect
    Beneficial
    Effect size
    Small

Adverse Events Reported

  • Red Grape→Overall tolerability

    Furthermore, the results of the incidence of adverse reactions did not differ between the flavonoids and the control group.

    Finding
    No significant difference
    Significant
    No
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