The effects of combination of Zingiber officinale and Echinacea on alleviation of clinical symptoms and hospitalization rate of suspected COVID-19 outpatients: a randomized controlled trial

Introduction

The pneumonia caused by COVID-19 has become a global highly infectious disease so that the virus is a serious threat to public health [1]. The World Health Organization declared the wide spread of the disease as a public health emergency. The virus responsible for the 2019–2020 pandemic is highly similar to severe acute respiratory syndrome (SARS). This contagious disease spreads through respiratory droplets and the common clinical symptoms are fever, dry cough, and tightness of breath that may lead to pneumonia, acute respiratory distress syndrome (ARDS), kidney failure, and multiple organ failure. Aged individuals with background conditions (e.g. asthma, diabetes, and heart failure) and weak immunity system are at more risk of infection by the virus [2], [3], [4].

Fighting the virus as an international emergency is seriously pursued in all countries. There is a bitter fight between the virus and human intelligence and brain power and winning this fight, along with taking protective and personal hygiene measures, entails taking proper control and timely therapeutic measures [5].

Most COVID-19 cases present influenza-like symptoms, and are hence eligible for outpatient or primary care management in first instance. However, most studies to date have focused on inpatient COVID-19 cases [6].

There is no specific anti-virus medicine for coronavirus and preservative cares including preserving vital signs, oxygen and blood pressure regulation, and alleviating the symptoms are the major approaches to treat the disease [7].

Herbal medicines, today, are considered as a way for treatment and preservation of health. Easy access and low prices of these medicines have added to the popularity of these medicines mostly in the developing countries. According to the National Administration of Traditional Chinese Medicine (NATCM), 90% of COVID-19 patients who received Qing Fei Pai Du Tang herbal medicine (a mixture of ginger, belamcanda, dioscoreae, glycyrrhiza glabra, etc.) showed positive responses to the treatment [8].

Among herbal medicines, Echinacea has been used for centuries for common cold, cough, bronchitis, upper respiratory system infection, and other inflammations. Studies have shown that Echinacea and its active compounds affect phagocyte immune system. Still, they do not affect special immune system. The medicine is used for viral, bacteria, radiation, and fungous infections. In addition, it is used as an anti-inflammatory [9]. Echinacea affects the immunity system from several aspects including increasing the count of white blood cells in the blood circulation system. Echinacea also improves phagocyte, improves lymphocytes activities, stimulates cytokine generation, and alleviates apoptosis. It stimulates macrophage activity and release of tumor necrosis factor (TNF), interleukin-1, interleukin-6, and interferon in vitro [10].

However, contradictory results have been published regarding the effect of Echinacea on increasing cytokines. In one study Echinacea increase significantly TNFa [11], whereas no effect on TNFa was for Echinacea in another study [12]. Also, in another study results support the Echinacea preparations are capable of neutralizing the virus-induced elevation in secreted chemokines and other cytokines and reversed the viral stimulation, thus providing a basis for the anti-inflammatory properties attributed to Echinacea [13].Contradictory results were obtained in cytokine, possibly due to different preparation used production[14].

There are also reports of antivirus activity against influenza, herpes simplex virus, and poliovirus. Phenol compound in Echinacea also demonstrates antioxidant activities [15].

Ginger is a key spice and a herbal medicine that is widely used. Suppressing synthesis of some of Proinflammatory cytokines such as interleukin-1, interleukin-8, and tumor necrosis factor alpha (TNF-alpha) are some of the effects of ginger. It also suppresses responses derived from T-helper1 activity [16].

A study showed that a mixture containing Zingiber officinale and Althaea officinalis extracts alleviated coughing, and the acute tracheitis-induced chest pain in patients [17]. Moreover, studies have shown that Zingiber officinale has anti-inflammatory effects and it is used for the treatment of arthritis rheumatoid and osteoarthritis [18], [19]. It was shown in [20] that Zingiber officinale was effective in alleviating asthma symptoms, although, it did not change the disease stage or spirometric indices.

Taking into account the potential effects of Zingiber officinale and Echinacea on alleviation of clinical symptoms in respiratory diseases, the study tries to examine the therapeutic effects of these two herbal medicines on hospitalization rate and the symptoms in suspected COVID-19 outpatients.

Methodology

Results

A total of 139 patients were screened for eligibility from April 2020 to June 2020. The whole trial was proceeded according to the Flow Chart (Figure 1).

Figure 1:

Flow-chart of study randomization, allocation, follow-up, and analysis.

The rate of adherence to drug treatment by patients participating in the study was complete. No specific side effects were reported during the study.

At baseline there were no statistically significant differences between the two groups in terms of the demographic characteristics (Table 1).

Baseline clinical symptoms for the 100 participants were evaluated (Table 2).

As shown in Table 2, all clinical symptoms of the two groups except cough were not significantly different at the beginning of the study. Because in data analysis, the rate of symptom improvement is compared in two groups, the difference in the frequency of cough in the two groups has no effect on the results.

Comparison of alleviation of clinical symptoms in control and treatment groups are presented in Table 3. In general, the results showed that the level of alleviation of coughing, muscular pain, and shortness of breath in the intervention group was better than that in the control group. There was no significant difference between the two groups in terms of other variables.

As shown in Table 3, 97.6% of patients in the intervention groups and 78.8% of the patients in the control groups had alleviated coughing problems after one week of the treatment. Chi squared test showed that this difference was significant (p value = 0.009) so that the rate of improvement of coughing problem in the intervention group was higher. The alleviation rate of muscle pain was 96%in the intervention group and 76.47% in the control group, which was also statistically significant (p value = 0.009). Also, 91.17% of patients in the intervention groups and 69.23% of the patients in the control groups had alleviated shortness of breath problems after one week of the treatment, which was statistically significant (p value = 0.02).

Table 4 lists the hospitalization rate in the two groups 14 days after the start of treatment.

As the results showed, hospitalization rate in the control and intervention groups was 6 and 2% respectively. Although, this rate was lower in the intervention groups, Chi squared test did not support a significant difference (Chi squared = 1.04, p value = 0.3).

Discussion

To the best of authors’ knowledge, this study is the first of its kind to survey the effects of Echinacea and Zingiber officinale in suspected COVID-19 outpatients. The results showed that adding the Echinacea and Z. officinale to the standard treatment protocol attenuated some of the clinical symptoms (coughing, shortness of breath, and muscle pain) in the subjects. Still, the hospitalization rate was not significantly changed.

In previous studies, researchers used Echinacea and ginger to treat respiratory diseases, separately. Echinacea shows in vitro antivirus activity against influenza virus and traditionally it is used to treat common cold and influenza [21], [22]. For instance, a study reported that Echinacea was as effective as oseltamivir in shortening the treatment duration of influenza. In addition, this medicine has a fewer side effects [21]. Another study reported that Echinacea significantly lowered the symptoms of common cold [23]. A study on the effects of Echinacea on prevention of acute respiratory infection in children at age range 1–5 years showed that there was a fewer incidence cases of upper air ways infections and sinusitis in the intervention group [24]. On the other hand, a clinical trial on patients inflicted by rhinovirus reported that in comparison with placebo, Echinacea did not alleviate the symptoms [25]. A metanalysis study showed that Echinacea decreased the incidence and duration of common cold [26]. Potentially, Echinacea decreases the risk of respiratory infections and the pertinent side-effects. Immunity adjustment, antivirus, and anti-inflammatory effects of Echinacea might help alleviation of clinical symptoms in respiratory patients [27]. Given the differences in methodologies and type of diseases under study, the findings by other studies are not perfectly comparable with the present study.

Ginger in traditional medicine is used for a wide range of diseases like asthma, arthritis rheumatoid, neural disease, diabetes, constipation, common cold, and influenza [28], [29]. A study on the effects of a mixture of Althaea officinalis and Zingiber officinale on bronchitis coughing showed the positive effects of the mixture in the form of less coughing attacks and chest pain caused by tracheitis (through alleviation of inflammation) [17]. Another study showed that ginger in asthma patients decreased the symptoms, while it did not change the stage of disease or spirometric results [20]. In [16], powdered ginger rhizome capsule as an add on inhalant corticosteroid and long-acting β2 agonist is effective in the improvement of forced expiratory volume at 1 s (FEV1), secondary efficacy variables were the peak expiratory flow (PEF), and the asthma control test (ACT) scores of the patients of a moderate type of persistent asthma uncontrolled on standard treatment.

In present study, hospitalization rate in the control and intervention groups was 6 and 2% respectively. In the study of Prieto-Alhambra et al. [6] the rate of hospitalization of COVID-19 outpatients was reported to be 15%. Of course, this study was a cohort study with prospectively collected data from the information system for research in primary care [6].

By prescribing Echinacea and Zingiber officinale herbal medicine simultaneously, the authors tried to improve synergistic effects of the medicines on strengthening the immune system and anti-inflammatory effects, which resulted in improving some of clinical symptoms of COVID-19 suspicious outpatients. Given the results, using the herbal medicines as a supplementary treatment for the patients is recommended. Alleviation of the symptoms like coughing, shortness of breath, and muscle pain in COVID-19 patients is highly important and needs low risk treatments that patients find them acceptable.

Conclusion

Taking into account the efficiency and minimal side-effects of Echinacea and Zingiber officinale, they are recommended for coronavirus outpatients. The authors hope that until the introduction of vaccine and specific drug for COVID-19, herbal medicine (Echinacea and Zingiber officinale) could help COVID-19 suspicious outpatients.