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.

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.