Investigating the effect of echinacea extraction syrup on the outcomes of lower respiratory infections in patients with COVID-19: a randomized clinical trial study

Abstract

Introduction

Many COVID-19 patients experience mild to severe symptoms, including respiratory system involvement. Different treatment instructions have been suggested for patients with COVID-19. Echinacea has known antiviral effects. However, there is still not enough evidence that it is effective in treating COVID-19. This study was conducted with the aim of determining the effect of Echinacea extract syrup on the outcomes of the lower respiratory tract in patients with COVID-19.

Methods

In this single-blind randomized controlled trial, 40 patients with COVID-19 who were inpatients in the hospitals of Mashhad University of Medical Sciences, Iran, were randomly selected and assigned to two equal control and experimental groups (n = 20). In addition to receiving routine care and treatment (oxygen supply, remdesivir, enoxaparin and heparin), the experimental group received 5 cubic centimeter (CC) of Imogen syrup three times a day for 5 days each. The control group only received routine care and treatment. The data were collected on the first, third and fifth days after hospitalization and were analyzed using descriptive and analytical tests in Statistical Package for the Social Sciences (SPSS). The significance level was set at p < 0.05.

Results

The mean white blood cell count in the experimental group after the intervention decreased significantly compared to that before the intervention (t = 0.434, p = 0.045, df = 19). Arterial oxygen pressure increased significantly in both the experimental group (t = 4.382, p = 0.000, df = 19) and control group (t = 3.239, p = 0.004, df = 19), however no statistical differences were observed between experimental and control groups after intervention. The level of lung involvement (p = 0.320) and cough symptoms (P = 0.347) were not significantly different between the experimental and control groups after the intervention. In addition, there were no significant differences between the experimental and control groups in terms of the mean oxygen saturation, temperature, and number of breaths per minute on the first, third, and fifth day (p > 0.05).

Discussion

The consumption of Echinacea extract syrup may not be able to improve the symptoms of acute lower respiratory tract infection in patients with COVID-19 with 3 daily doses for 5 days. More studies should be conducted to investigate the clinical effects of Echinacea extract in the treatment of patients with pulmonary complications.

Trial Registration

IRCT20130522013423N2.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12985-024-02586-6.

Introduction

An outbreak of pneumonia associated with a novel coronavirus (SARS-CoV-2), severe acute respiratory syndrome coronavirus 2, was reported in Wuhan, Hubei Province, China, in December 2019, and infections have since spread throughout China and other countries around the world [1]. SARS-CoV-2 is an RNA virus genetically classified in the beta coronavirus genus that uses a glycoprotein (spike protein) to bind to the angiotensin-converting enzyme II (ACE2) receptor. After binding, the transmembrane protease serine 2 (TMPRSS2) facilitates the entry of the virus into the host cell [2]. Overall 30 to 60% of patients who shed the virus may have no symptoms. The risk of infection and severe symptoms is greater in the elderly population and among people with comorbidities. Symptoms usually appear between 2 and 14 days after exposure. Approximately 80 to 90% of infections are mild or moderate, and many may be asymptomatic. Shortness of breath can occur within weeks after the onset of symptoms in approximately 40% of symptomatic patients [3].

With the emergence of SARS-CoV-2 infection, many related diseases, such as pneumonia, acute and chronic respiratory diseases, and digestive, kidney and central nervous system diseases, have spread. Although many antiviral drugs are used to treat SARS-CoV-2 infection, an agreed and definitive therapeutic management is not available. Currently, treatment management to fight against COVID-19 includes antiviral treatments such as remdesivir and immunosuppressive drugs such as dexamethasone. Lopinavir–ritonavir (LPV/r), which is used to treat human immunodeficiency virus (HIV), is also prescribed for antiviral treatment of COVID-19. Evidence on the use of LPV/r for viral clearance, time to clinical improvement, and mortality is conflicting [4].

Many treatment guidelines have been published for the management and treatment of patients with COVID-19 that are based on the recommendations and opinions of experts and some scientific evidence. These guidelines are very similar across countries, and treatment consists of four main groups of drugs: antiviral, systematic corticosteroids, antimalarial, and antibiotics, which are prescribed in a variety of drugs, doses, and durations [4]. In addition, numerous nonpharmacological preventive and supportive strategies, including isolating patients and social distancing, have been proposed to reduce the spread of the disease. There is no definitive agreed-upon drug protocols for the treatment of COVID-19 [5].

Additionally, antiviral drugs currently used to treat patients with COVID-19 have side effects and can endanger the health of patients. As the overall mortality and length of hospital stay show, the remdesivir, hydroxychloroquine, lopinavir and interferon regimens have little effect or no effect on hospitalized patients [6]. On the other hand, the cost of the course of treatment for COVID-19 with most of these drugs is very expensive for many countries, especially in low-income countries, which limits their access to patients [4]. In this context, medicinal plants have been used as a source of medicine in almost all cultures since ancient times. Today, in most developing countries and even in industrialized societies, medicinal plants are widely used to maintain health, and several chemical drugs have been extracted from these plants. In developing countries, the use of local traditions and beliefs is still the mainstay of health care, the use of medicinal plants to treat diseases is almost universal, and many herbal medicines, including phenols, polysaccharides, flavonoids, alkaloids and terpenes, have been used since ancient times. Each of these compounds has a different function in preventing and treating viruses [7].

Echinacea is one of these plants, and its derivatives possess antiviral properties against influenza, herpes, and polioviruses. Echinacea extract is rich in alkyl amides that activate macrophages, support healthy immune responses, and modulate cytokine secretion, and support respiratory system function and health. Its products activate macrophages and substances such as TNF, interleukin 1, interleukin 6, and interferon. [8]. Studies show that Echinacea may reduce the severity and duration of respiratory tract infections, representing a potential candidate for reducing the symptoms of COVID-19 [9, 10]. One of the important effects of Echinacea is to stimulate the immune system including increased chemotaxis, phagocytosis, and oxidative bursts of macrophages or neutrophils [11].

The relative effect of cold treatment on this plant has been observed, but more studies are needed to obtain more accurate information [9]. Today, Native Americans use Echinacea as an herbal medicinal supplement to treat cold and flu symptoms. The Echinacea plant is one of the best-selling perennial plants in the United States [10]. Most of the research on Echinacea plants has been performed in Germany, and the German Health Organization has approved the use of Echinacea as an adjunctive treatment for respiratory tract infections, urinary tract infections and wounds [11]. Echinacea is known as a supplement and booster of the immune system in the body’s defense against infections caused by SARS-CoV-2, but the use of these supplements is still controversial [12].

Regardless of the extract and its products, the Echinacea plant is considered an immune response enhancer and is effective in preventing and treating colds, flu, and infections of the upper respiratory tract and urinary system [13]. In a study under laboratory conditions, the fortified extract of Echinacea inhibited types of SARS-CoV, SARS-CoV-2 and MERS-CoV [14]. To date, no studies have been conducted on the use of Echinacea for the prevention or treatment of conditions similar to COVID-19. Therefore, the present study investigated the effect of Echinacea extract syrup on the outcomes of lower respiratory system infections in patients with COVID-19.

Methods

Study design and participants

This study, which is in accordance with CONSORT guidelines, is a single-blind randomized controlled trial that was conducted on 40 patients in the inpatient wards of COVID-19 patients in hospitals affiliated with Mashhad University of Medical Sciences, Mashhad, Iran. In this study, 4 hospitals were selected from among 7 hospitals affiliated with Mashhad University of Medical Sciences using the cluster sampling method. These hospitals provide all medical and care services for patients with similar socioeconomic conditions. Then, 2 hospitals were selected by lottery. One hospital was assigned to the experimental group and one hospital to the control group. Finally, according to the study inclusion criteria, patients were selected from the list of patients admitted to the inpatient department for COVID-19 patients in each hospital (Fig. 1).

Fig. 1.

Consort flow diagram

Inclusion and exclusion criteria

The inclusion criteria included the following: 1- positive PCR test, 2- involvement of the lower pulmonary system, 3- no contraindication to Imogen Syrup, 4- willingness to participate in the study, 5- Over 30 years old and 6- definitive diagnosis of COVID-19 based on evidence. The exclusion criteria included the following: 1- possible sensitivity to Imogen Syrup, 2- presence of nervous system and autoimmune diseases, 3- deformity in the chest, and 4- acute conditions of the patients during the study.

Sample size

In this study, considering that similar studies were not available, the sample size was determined by conducting a preliminary study on 20 patients (10 people in the experimental group and 10 patients in the control group). The sample size was calculated for each of the study variables (cough, sore throat, fever and chills). Considering that the highest frequency was related to cough, the sample size of 18 was calculated for each group. Of course, due to possible dropout, 20 people in each group were included in the study.

Recruitment

Out of 4 randomly selected hospitals, 1 hospital was assigned to the experimental group and 1 hospital was assigned to the control group. In these hospitals, 57 patients for the experimental group and 57 patients for the control group were registered using the list of admitted patients. People who wanted to participate in the study were enrolled after providing written consent and screening. After completing the informed consent form by the subjects and ensuring that they understood the purpose of the study and that they could leave the study at their own will, they were screened. The screening parameters included demographic and clinical information, medical history, and vital signs.

Randomization and blinding

In this research, we used a table of random numbers that were generated using computer program for randomization. The numbers are shown from left to right. For concealment, opaque sealed envelopes with random sequences were used. For sample selection, one envelope was assigned to each patient. Even numbers in both groups were assigned to the participants of the experimental and control groups. Data collector and data analyzer are kept blind to the information of study groups.

Intervention

In this study, the experimental group from the first day of hospitalization; 5 cc of Echinacea extract syrup (Immugen), a herbal medicine made by the Kimia Daru factory, used thrice daily for 5 days in the hospital. This group of patients also received drugs and routine care methods. This syrup contains Echinacea purpura extract (250 mg per 5 ml equivalent to 1000 mg of dry herb per 5 ml syrup). Other ingredients include xanthan gum, citric acid, sorbitol, potassium sorbate, cocoa, orange essence. Its dosage is different for different ages. For people over 12 years of age and adults, 5 ml (one tablespoon) of the syrup with an adequate amount of liquid (water or fruit juice) 3 times a day as prescribed by the doctor. This product is sold under the Immugen brand in a 120 ml PET bottle package with a box and brochure. The control group receives treatment and care based on the department’s routine protocols. These protocols included supportive treatments such as oxygen supply through cannula, facemask, venturi mask and drug treatment including antiviral drug remdesivir, hydrocortisone and anticoagulant drugs such as enoxaparin and heparin.

Clinical outcomes

The primary outcomes were two categories, including primary clinical outcomes and Para clinical outcomes. The primary clinical outcomes were symptoms of severity of infection in the lower respiratory tract, including temperature and cough symptoms. Cough symptom was evaluated on the first day of hospitalization and on the fifth day of hospitalization. Temperature was evaluated on the first day of hospitalization, the third day, and the fifth day of hospitalization. Para clinical outcomes included saturated oxygen, blood oxygen pressure, white blood cell count, extent of lung involvement, and breaths rate per minute. The number of breaths per minute was evaluated on the first, third, and fifth days of hospitalization, and blood oxygen pressure, white blood cell count, and extent of lung involvement were evaluated on the first and fifth days of hospitalization.

Data collection and clinical follow‑up

In this study, demographic data and data related to patients’ diseases, such as patient conditions, disease history, history of hospitalization, drugs and medical treatments, test results and lung X-rays, were collected from the electronic registration dataset of patients admitted to the hospital at the time of hospitalization. The results of tests were collected on the first, third and fifth days of hospitalization, and lung x-rays were collected on the first and the fifth day.

Data analysis

The data were analyzed using SPSS version 22 software. First, the distribution of the variables was determined by the Kolmogrov-Sminov test. Then, descriptive statistics were used to determine the characteristics of the study participants. The chi-square test was used to determine the homogeneity of qualitative variables between two groups. Independent t tests were used for normally distributed quantitative variables and nonparametric tests were used for nonnormally distributed variables. For the variables that were evaluated more than twice, including the number of breaths per minute, saturated oxygen, and temperature that were evaluated on the first, third, and fifth days of hospitalization, repeated measures ANOVA test was used to show the effect of time on the intervention. P < 0.05 was regarded as level of statistically significant.

Results

Sample characteristics

The average age of the participants in the experimental and control groups was 62.15 ± 16.32 (Max = 90.0, Min = 30.0) and 58.95 ± 15.42 (Max = 81.0, Min = 32.0), respectively, and there was no significant difference between them (t = 0.68, df = 38, p = 0.484). As shown in Table 1, the results of the chi-square test showed that before the intervention, there was no significant difference between the two groups in terms of educational variables, employment status or other demographic variables.

Table 1.

Frequency of demographic variables and medical history in intervention and control groups

Variables		Study groups		Test statistics * P-value
		Echinacea syrup	Control
Gender	Female	10 (50.00)	12 (60.00)	χ2 = 0.404 P = 0.751
	Male	10 (50.00)	8 (40.00)
Employment status	Housekeeper	7(35.00)	9 (45.00)	χ2 = 1.276 P = 0.935
	Employee	1 (5.00)	2 (10.00)
	Free job	8 (40.00)	5 (25.00)
	Retired	2 (10.00)	2 (10.00)
	Other	2 (10.00)	2 (10.00)
Education (years)	Illiterate	5 (25.00)	7(35.00)	χ2 = 0.644 P = 0.891
	Elementary and less than diploma	5 (25.00)	4 (20.00)
	Diploma	7(35.00)	7(35.00)
	Academic	3(15.00)	2 (10.00)
History of the underlying disease	Had	8 (40.00)	9 (45.00)	χ2 = 1.600 P = 0.343
	has not had	12 (60.00)	11 (55.00)
History of using tobacco and other tobacco products	Had	8 (40.00)	10 (50.00)	χ2 = 1.540 P = 0.894
	has not had	12 (60.00)	10 (50.00)
History of readmission	Had	4 (20.00)	3 (15.00)	χ 2 = 0.173 P = 0.500
	has not had	16 (80.00)	17 (85.00)

^*chi-square test

Intervention findings

The results of the independent t tests in Table 2 show that the mean white blood cell counts before the intervention did not differ significantly between the experimental and control groups. Also, the independent t-test results show that the mean white blood cell counts after the intervention is not significantly different between the experimental and control groups. The paired t test showed that the mean white blood cell count in the experimental group after the intervention decreased significantly compared to that before the intervention (p = 0.045). However, in the control group, the decrease in the mean white blood cell count after the intervention was not significant compared to before the intervention.

Table 2.

The mean of oxygen pressure and white blood cell count between the experimental and control groups

variables	Study groups	Before Intervention	After Intervention	Test statistics ** P-value
		Mean (SD)	Mean (SD)
White blood cell count (cells/µL)	Echinacea syrup	10.70 (4.29)	9.20 (4.29)	t = 0.434 df = 19 p = 0.045
	Control	10.80 (4.75)	10.75 (5.00)	t = 0.062 df = 19 p = 0.952
Test statistics *P-value		t = 0.070 p = 0.945	t = 0.999 p = 0.324
Oxygen pressure (mmHg)	Echinacea syrup	57.95 (17.43)	72.40 (14.63)	t = 4.382 df = 19 p = 0.000
	Control	46.55 (19.48)	59.35 (17.37)	t = 3.239 df = 19 p = 0.004
Test statistics *P-value		t = 0.271 p = 0.014	t = 1.950 p = 0.060

^* Independent t-test

^** Paired sample t test

The independent t-test showed a significant difference in the average arterial oxygen pressure between the experimental and control groups before the intervention (p = 0.014), but there was no significant difference in the average arterial oxygen pressure between the two groups after the intervention (p = 0.060). The results of the paired t test showed that the arterial oxygen pressure in the experimental group (p = 0.000) and control group (p = 0.004) increased significantly, after the intervention compared to before the intervention (Table 2).

In Table 3, the results of the repeated measures ANOVA show that despite the significant increase in mean oxygen saturation over time (time effect; p = 0.000), there was no significant difference between the experimental and control groups (time*group effect; p = 0.581). And despite the significant decrease in temperature over time (time effect; p = 0.037), there was no significant difference between the experimental and control groups (time*group effect; p = 0.413). Additionally, despite the significant decrease in the average number of breaths per minute over time (time effect; p = 0.000), here was no significant difference between the experimental and control groups (time*group effect; p = 0.434).

Table 3.

Mean of oxygen saturation, temperature, and number of breaths per minute on the first, third, and fifth days in the experimental (N = 20) and control groups (N = 20)

Variables	Study groups	Days of hospitalization			* Test statistics P-value
		The first day	The third day	The fifth day	Time	Time*group
		Mean (SD)	Mean (SD)	Mean (SD)
Saturated oxygen (%)	Echinacea syrup	91.10 (7.03)	91.80 (5.77)	95.05 (2.32)	F = 12.381 p = 0.000	F = 0.547 p = 0.581
	Control	87.15 (13.09)	89.20 (9.99)	90.95 (9.99)
Temperatures (°C)	Echinacea syrup	38.90 (6.17)	35.75 (7.96)	35.30 (8.08)	F = 1.446 p = 0.037	F = 0.896 p = 0.413
	Control	34.55 (11.16)	33.90 (11.09)	33.55 (1.02)
Breaths per minute	Echinacea syrup	21.85 (5.84)	18.40 (4.18)	17.85 (3.91)	F = 13.908 p = 0.000	F = 0.844 p = 0.434
	Control	21.80 (6.05)	21.86 (5.62)	21.85 (5.35)

* Repeated measures ANOVA; Tests of within-subject’s effects

The results of the Fisher exact test in Table 4 show that in the experimental and control groups before the intervention, there was a significant difference in the extent of lung involvement. The results showed that in both the intervention and control groups after the intervention, the extent of lung involvement was limited and without involvement or clear and there was no significant difference between the two groups. In addition, the results showed that before the intervention, there was no significant difference between the patients in the test and control groups in terms of the presence of cough symptoms. After the intervention, there was no significant difference between the test and control groups.

Table 4.

Comparison of the frequency of lung involvement in experimental and control

Variables			Study Groups		*Test statistic P-value
			Echinacea syrup (N = 20)	Control groups (N = 20)
Extent of lung involvement	Before Intervention	Wide	1 (2.50)	9 (22.50)	p = 0.007
		Limited	12 (30.00)	9 (22.50)
		No conflict/clear	7 (17.50)	2 (5.00)
	After Intervention	Wide	0 (0.00)	0 (0.00)	P = 0.320
		Limited	5 (25.00)	9 (45.00)
		No conflict/clear	15 (75.00)	11 (55.00)
cough symptom	Before Intervention	Yes	5 (12.50)	6 (30.00)	P = 0.500
		No	15 (37.50)	14 (70.00)
	After Intervention	Yes	3 (15.00)	5 (12.50)	P = 0.347
		No	17 (85.00)	15 (37.50)

^*Fisher Exact test

Discussion

In this study, the clinical effectiveness of Echinacea extract syrup was investigated over a 5-day period of use in hospitalized patients with symptoms of lower respiratory system infection. In our study, there was a significant decrease in the mean of white blood cell counts in the experimental group before and after intervention. Contrary to our findings, the evidence identified that Echinacea can help the immune system fight infections by stimulating the production of white blood cells. This effect can temporarily increase the number of white blood cells [15, 16]. It can also regulate immune system activity, potentially helping to balance the number of white blood cells in the body [17]. Studies also indicate that Echinacea can activate innate immune cells by increasing the amount of immune cells, the ability of macrophages to phagocytose, migrate granulocytes, and increasing cytokine production, as well as cytotoxicity of natural killer cells [12, 18, 19]. In another study, Echinacea was given to common cold patients in the experimental group at the onset of a cold for 7 days, with eight doses (5 ml per dose) on the first day and three doses on subsequent days. The results showed that Echinacea consumption increased white blood cells, neutrophils, and monocytes [20]. Several reasons can cause the decrease of white blood cells in the intervention group with Echinacea consumption. Among these cases, we can mention the dose of Echinacea received by the patients or the duration of receiving it.

Barrett et al. studied 719 patients with colds in four groups with the aim of determining the effect of different doses of the dried root of Echinacea plant on the severity of symptoms and other outcomes, such as interleukin 8 and neutrophil count, over a period of 4 days. These findings showed that this dose of Echinacea formula does not have significant effects on the symptoms or consequences of cold [21].

In another clinical trial on children with acute lymphoblastic leukemia, it was also shown that the use of Imogen syrup containing Echinacea root extract for 3 months can prevent symptoms of upper respiratory infections [22].

In our study, arterial oxygen pressure significantly increased in both the experimental and control groups, and there were no significant differences between these groups after intervention which indicated improvement of the disease over time, independent of the treatment with Echinacea. The significant increase in both the test and control groups could be due to the use of respiratory support, such as oxygen therapy, that they received normally. This can also be caused by the nature of the disease or the protocol of Echinacea syrup consumption. These findings were inconsistent with the study of Ding et al., who studied glycyrrhetinic acid and its derivatives as complementary and alternative medical approaches to control and inhibit the symptoms of COVID-19 in nonhospitalized patients. These researchers reported that after 12 h of consuming the solution, the patient’s respiratory symptoms, such as cough, shortness of breath and arterial oxygen saturation, improved [23]. In the second stage of COVID-19, pulmonary complications occur, which usually last between 5 and 13 days. At this stage, pulmonary symptoms first occur without hypoxia and later develop into hypoxia. Moreover, the potential of the innate immune system to fight infection is also threatened, and patients often present to the hospital at the end of stage 1 or the beginning of stage 2 [24].

In our study, consumption of Echinacea extract syrup did not cause a significant decrease in the number of breaths per minute on the first, third and fifth days in the experimental group compared to the control group. In a meta-analysis that examined the effects of Echinacea syrup on the prevention and treatment of upper respiratory infections, the findings showed that Echinacea not only is safe for short-term use but can also prevent the occurrence of upper respiratory infections. This study, similar to our findings, did not reveal strong results for the clinical effects of Echinacea [25]. In the study by Mesri et al. (2021), which examined the effect of the combination of ginger and Echinacea on the clinical symptoms of patients suspected of having COVID-19, symptoms such as cough, muscle pain, and shortness of breath differed between the experimental group and the control group. Most of the patients in the experimental group showed a reduction in cough symptoms after one week [24]. In Rahmati et al.’s study, symptoms such as fever, cough, and nasal discharge were investigated in children with colds. In a large number of patients, after a short period of taking Immugen Syrup, the symptoms decreased or stopped. However, there was no significant difference between the test and control groups [26].

In the present study, there was no significant difference in the body temperature of the participants on the first, third and fifth days of consuming Echinacea between the experimental group and the control group. In the study of Rauš et al. (2015), which was conducted on 473 patients with early flu symptoms, there was no significant difference in the symptoms of the disease, including axillary temperature, between the group receiving the Echinaforce Hotdrink and the group receiving oseltamivir [27]. Additionally, Huseini et al. (2020), studied 60 patients with COVID-19 with the aim of determining the effect of the combined drug Imfluna (containing Echinacea) on the symptoms and signs of the disease; symptoms such as shortness of breath, cough and fever decreased in the test group [28]. In these studies, the decrease in clinical symptoms may be due to the combined use of Echinacea tablets and a longer follow-up period compared to the present study.

In the present study, the severity of lung involvement in the experimental group did not decrease significantly after the intervention compared to before the intervention. Studies have shown that treatment with Echinacea can reduce the symptoms of acute respiratory infections, the severity of infection and the duration of acute respiratory infections, especially when it is prescribed at the beginning of the symptoms of infection [19]. In a study by Signer et al. (2020), HCoV-229E was irreversibly inactivated by direct contact with Echinaforce. However, pretreatment of the cell lines did not inhibit infection with HCoV-229E, and post infection treatment had only a marginal effect on viral shedding. However, it has a protective effect on all CoVs [14]. Unlike the present study, the results of these studies, which were conducted with the aim of preventing acute upper respiratory infections by consuming Echinacea for a long period, show that consuming Echinacea for a long period can have significant preventive effects.

The results of this study showed that although fewer patients experienced cough symptoms after the intervention, than before the intervention, no significant difference was observed in the frequency of patients with cough symptoms. These findings are contrary to the findings of Rauš et al. (2015), who reported that a hot Echinacea drink had a positive effect on reducing cough in patients consuming this drink [27]. On the other hand, other studies have shown that the use of Echinacea extract can reduce respiratory symptoms such as cough [24, 28]. The difference between the results of this study and those of previous studies may be because the extracts extracted from different parts of the plant and the methods used for plant preparation have different effects. Additionally, combining Echinacea with other herbal products or other substances can have different effects. On the other hand, the duration of intervention and follow-up in the present study are different from those in these studies, and different results can be produced.

Limitations

This clinical trial has limitations and strengths. One of the strengths of our study is that as soon as the patients were hospitalized, we included them in the study. It was possible to evaluate the effects of the intervention from the beginning of the intensification of the symptoms of the disease. Also, the study addresses a relevant question regarding the potential use of alternative treatments for COVID-19. On the other hand, our study was a single-blind randomized controlled trial with a small sample size. And patients were followed up for 5 days after hospitalization, and the effects of Echinacea extract syrup were not investigated for a longer duration or a higher dose. Additionally, this study was conducted on patients who did not have any underlying disease, and the severity of the infection was not severe. Therefore, the results cannot be generalized to all patients with different disease conditions. It is suggested that future studies should be conducted with double-blind randomized controlled trial with a small sample size and longer follow-up period. And patients with a history of underlying and chronic diseases should also be included. Additionally, different methods for the preparation of Echinacea extract have different effects. The effects of Echinacea in combination with other herbal compounds and supplements should be studied for the control and treatment of COVID-19.

Conclusion

In conclusion, the consumption of Echinacea extract syrup without negative side effects, may not be able to improve the symptoms of acute lower respiratory tract infection in patients with COVID-19 with 3 daily doses for 5 days. More studies are necessary to confirm the strong clinical efficacy of Echinacea extract syrup.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Abbreviations

CC

Cubic centimeter

SPSS

Statistical package for the social sciences

Author contributions

Mo.M, M.Y, F.R, E.KH and M.M contributed to the development of this study protocol. This manuscript was prepared by Mo.M and E.KH and reviewed, edited by M.Y and SS.RS. All authors approved the final version.

Funding

None.

Data availability

Data is provided within the manuscript or supplementary information files.

Declarations

Ethics approval and consent to participate

The protocol has been registered with IRCT code IRCT20130522013423N2 and has been approved by the Human Research Ethics Committee of Mashhad University of Medical Sciences under the code IR.MUMS.REC.1401.013. In this randomized controlled trial, the principles stated in the Declaration of Helsinki were followed. All patients provided written informed consent and were informed about the purpose and possible outcomes of the study. The participants were also informed that their information would be kept confidential and that they would have the right to withdraw freely from the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.