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. 2026 Feb 16;18(2):303–311. doi: 10.1016/j.chmed.2026.02.016

Efficacy and safety of Toujie Quwen Granules in patients infected with SARS-CoV-2: A prospective cohort study of 156 cases

Qihua Xu a, Xinyue Zhang a, Sanqi Huang b, Linghua Li b, Feng Li b, Wei Liu c, Kunzhou Ling b, Jialong Guan b, Xinghua Tan b,⁎, Luping Lin b,⁎
PMCID: PMC13069607  PMID: 41971596

Abstract

Objective

Given traditional Chinese medicine (TCM)’s efficacy in influenza and severe acute respiratory syndrome (SARS), it was adopted clinically in the early stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection outbreak in China. However, the therapeutic effects of Toujie Quwen (TJQW) Granules in treatment of (SARS-CoV-2) infection have not been fully elucidated. This study aimed to investigate the efficacy and safety of TJQW in patients infected with SARS-CoV-2 and provide evidence for clinical practice of TCM.

Methods

A cohort study was conducted on SARS-CoV-2 infection admitted between 20 January and 15 March 2020. Patients were divided into two cohorts based on their clinical medication plan: TJQW combined with Western medicine (TJQW + WM) group and Western medicine (WM) group. The WM group received conventional WM treatment (antibiotics, glucocorticoids, oxygen therapy, arbidol, chloroquine, lopinavir/ ritonavir, ambroxol hydrochloride), while the TJQW + WM group received TJQW in addition to WM (15 g/bag, two bags at a time, three times a day). The incidence of severe disease and chest computed tomography (CT) findings before and after treatment were compared between groups. Dynamic analysis was performed on white blood cell (WBC) count, lymphocyte count (LYM), lymphocyte percentage (LYM%), Krebs von den Lungen 6 (KL-6) and symptom scores within 15 d of enrolment.

Results

Six cases in the TJQW + WM group progressed to severe disease, with an incidence of 7.89% (6/76), while 16 cases in the WM group progressed to severe disease, with an incidence of 20% (16/80, P = 0.025), and the difference was significant. The CT scores of the TJQW + WM group decreased continuously from day 6 of disease onset and were significantly lower than those of the WM group on days 12 and 15, with significant differences. On day 12 of the disease, the improvements in WBC and LYM in the TJQW + WM group were superior to those in the WM group, with significant differences. The KL-6 levels of the two groups were compared by fitting the data to a generalised linear model. After controlling for the effects of time from onset to detection, the KL-6 level of the TJQW + WM group was significantly lower than that of the WM group (t = 3.703, P < 0.01). Repeated measures analysis of variance was performed on the total score of major symptoms and showed insignificant differences (F = 0.031, P = 0.871). However, there was an interaction effect between treatment plan and treatment duration, with significant differences in the degree of change at each time point for the global scores (F = 6.502, P < 0.01). The TJQW + WM group showed a better improvement in symptoms and a reduction in the expression of inflammatory factors than the WM group.

Conclusion

TJQW could effectively decrease the incidence of severe disease, reduce pulmonary inflammation and fibrosis, and alleviate clinical symptoms.

Keywords: CT scores, inflammatory factors, KL-6, SARS-CoV-2 infection, Toujie Quwen Granules, traditional Chinese medicine

1. Introduction

Since the first case of SARS-CoV-2 infection was identified in 2019, over 775 million people had been infected and seven million deaths worldwide reported as of May 2024 (WHO, 2024). Its causative agent, SARS-CoV-2, is an RNA virus belonging to the coronavirus family that can cause a range of human illnesses, including asymptomatic carriage, an upper respiratory illness, and fulminant respiratory failure. The long-term effects of infection remain an active area of research (Lai et al., 2023, Xie et al., 2022, Xu et al., 2022).

At the beginning of the SARS-CoV-2 infection pandemic outbreak, from the end of 2019 to the beginning of 2020, due to the delay in the development and use of targeted antiviral drugs and vaccines, the Chinese government adopted a combination of TCM and modern medicine, which has achieved good efficacy in the clinical treatment of SARS-CoV-2.

Throughout Chinese history, there have been more than 300 recorded outbreaks of epidemics in China since the Han Dynasty. TCM has played an important role in the treatment and management of these epidemics for thousands of years. After a long history of accumulation, TCM has developed a mature set of epidemic disease treatment and management system, which has been effectively applied to the treatment and management of SARS-CoV-2 infection. Unlike modern medicine which focuses on the virus itself, TCM places greater emphasis on understanding the characteristics and evolution of the disease, identifying the pattern of the disease by collecting various symptoms and signs, and then prescribing the appropriate medicine for the disease, which is the prerequisite for formulating a scientific treatment plan. In general, in the clinical practice of treating SARS-CoV-2 infection, TCM has advantages in accessibility and can improve clinical symptoms, shorten the duration of hospitalization, reduce the rate of progression and overall mortality, and shorten the negative transition time of nucleic acid test for SARS-CoV-2. These results have important reference value for the control of the epidemic in the future.

Patients infected with SARS-CoV-2 present with a variety of symptoms including cough, fever, malaise, myalgia, gastrointestinal symptoms, ageusia, and anosmia; some individuals progress to acute respiratory distress syndrome and death. Severe disease usually occurs approximately one week after the onset of symptoms and can develop rapidly from mild symptoms (Berlin, Gulick, & Martinez, 2020). Risk factors for severe SARS-CoV-2 infection include being male, older age, and having cardiovascular disease, lung disease, hypertension, diabetes, or obesity (Williamson et al., 2020, Wu et al., 2020). The current lack of antiviral drug therapies or vaccine prevention with confirmed efficacy has led to significant difficulties in managing this disease (Zhou et al., 2021). Given the large number of severe and fatal cases, finding different means to effectively block disease progression and reduce the incidence of severe disease is the focus and challenge of treatment in SARS-CoV-2 infection. Previous reports have confirmed that integrated TCM can increase the clinical efficacy rate, improve clinical symptoms, shorten hospital stay and reduce severe and critical cases. Accumulating evidence indicates that early and timely intervention of SARS-CoV-2 infection patients with TCM has a positive significance in improving the cure rate, shortening the disease course, delaying the disease progression and reducing the mortality rate (Jiang et al., 2021, Tian et al., 2020).

Guangzhou Eighth People’s Hospital, the designated hospital for the treatment of SARS-CoV-2 infection in Guangzhou, has established a TCM research team in collaboration with the TCM Department of Fujian Provincial Hospital. Based on the characteristics of SARS-CoV-2 infection patterns they elucidated, the research team further proposed that SARS-CoV-2 infection is a“heat-toxin plague”. This understanding has enriched the theoretical framework of TCM treatment of SARS-CoV-2 infection and provided guidance for clinical diagnosis and treatment. Through in-depth analysis of the etiology and pathogenesis of SARS-CoV-2 infection, and based on the previous experience in treating acute respiratory infectious diseases, the “Pneumonia Prescription No. 1” (now renamed as Tongjie Quwen Granules) was developed. The objective of this study was to investigate the efficacy and safety of Toujie Quwen Granules in 156 SARS-CoV-2 infected patients.

2. Methods and materials

2.1. Participants

SARS-CoV-2 infection was diagnosed according to the New Coronavirus Pneumonia Diagnosis and Treatment Program (5th version) (National Health Commission, 2020) published by the National Health Commission of China. This study conducted a prospective cohort study that adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all patients enrolled in the study. The study was registered in the Chinese Clinical Trial Register (registration number: ChiMCTR2000003144, ChiCTR2000031089) and approved by the Ethics Committee of Guangzhou Eighth People’s Hospital (approval number: 202010143).

2.2. Inclusion and exclusion criteria

Inclusion criteria consisted of following: 1) The study included patients who met the criteria for SARS-CoV-2 infection; 2) Both male and female patients aged 16–80 years (inclusive); 3) Hospitalized within ≤10 days of symptom onset.

Participants who met any of the following conditions were excluded from the study: 1) Patients for whom oral or nasal administration is difficult, allergic or intolerant to TJQW; 2) Medication compliance cannot be guaranteed during treatment; 3) Patients with severe primary respiratory disease or pneumonia caused by other pathogens; 4) Patients with serious diseases, malignant tumours or mental diseases; 5) Pregnant women or urine pregnancy test positive; 6) Participated in other drug trials in the past month; 7) The investigator considered the patient to be unsuitable for the study; 8) Hospitalization >10 d after symptom onset.

2.3. Cohort grouping and treatment plan

This study enrolled a total of 156 patients that diagnosed with SARS-CoV-2 infection who were admitted to Guangzhou Eighth People’s Hospital between 20 January and 15 March 2020. Patients were divided into two cohorts according to their clinical drug regimen: TJQW Granules plus Western medicine (TJQW + WM) group and the Western medicine (WM) group. Patients chose one of treatments and signed the informed consent form. Both groups were treated for 6–12 d. Nurses monitored patients to ensure they took their medication on time, and two or more deputy chief TCM doctors are responsible for daily ward rounds.

2.4. WM and TJQW Granules treatments

WM treatments included: isolation, nursing care, bed rest, symptomatic and supportive treatment. The detailed course of administration was as follows: Arbidol Hydrochloride Tablets (Shiyi Pharmaceutical Group Ouyi Pharmaceutical Co., Ltd, batch No. 386191102, 0.1 g/tablet), 0.2 g each time, three times a day; Moxifloxacin Hydrochloride Tablets (Beijing Fuyuan Pharmaceutical Co., Ltd, State Pharmaceutical Licence No. H20183096, 0.4 g/tablet), 0.4 g each time, one time a day; Ambroxol Hydrochloride Tablets (Yangzhou City Sanyu Pharmaceutical Co., Ltd, State Pharmaceutical Licence No. H20000280, 30 mg/tablet), 30 mg each time, three times a day.

Chloroquine Phosphate Tablets (Sichuan Otsuka Pharmaceutical Co., Ltd, State Pharmaceutical Licence No. H51020072, 250 mg/tablet), 500 mg each time, twice daily; Lopinavir and Ritonavir Tablets (AbbVie Deutschland GmbH & Co. KG, State Pharmaceutical Licence No. HJ20170213, 200 mg/50 mg/tablet), two tablet each time, two times daily.

TJQW Granules were provided by EFONG Pharmaceutical Co., Ltd. (Foshan, China). Composition of TJQW granules: Forsythiae Fructus (Lianqiao in Chinese), Cremastrae Pseudobulbus Pleiones Pseudobulbus (Shancigu in Chinese), Lonicerae Japonicae Flos (Jinyinhua in Chinese), Scutellariae Radix (Huangqin in Chinese), Isatidis Folium (Daqingye in Chinese), Bupleuri Radix (Chaihu in Chinese), Artemisiae Annuae Herba (Qinghao in Chinese), Cicadae Periostracum (Chantui in Chinese), Peucedani Radix (Qianhu in Chinese), Fritillariae Cirrhosae Bulbus (Chuanbei in Chinese), Fritillariae Thunbergii Bulbus (Zhebei in Chinese), Mume Fructus (Wumei in Chinese), Scrophulariae Radix (Xuanshen in Chinese), Astragali Radix (Huangqi in Chinese), Poria (Fuling in Chinese), and Pseudostellariae Radix (Taizishen in Chinese). The production batch number of TJQW Granules is 9115313, the preparation approval number is Z20200009000 and the license number (Guangdong): 20160214. The drug has been identified by EFONG Pharmaceutical and the Pharmacy Department of Guangzhou Eighth People’s Hospital. TJQW Granules preparation as follow: Above 16 flavors, take Fritillariae Cirrhosae Bulbus to crush, set aside; The volatile oil was extracted from Forsythiae Fructus, Bupleuri Radix, and Peucedani Radix, and the residue and the other 12 flavors were decocted twice with water. The first time was added with seven times water for 1 h, the second time was added with seven times water for 1 h, filtered, combined with the filtrate, concentrated to the relative density of 1.07−1.10, dried, Add the above mentioned Fritillariae Cirrhosae Bulbus powder, silica, stevioside and dextrin, mix and make granules; add the above mentioned volatile oil, mix and make 1000 g. In order to ensure the stability and uniformity of TJQW Granules, A method for the determination of forsythiside A in Forsythiae Fructus and baicalin in Astragali Radix in TJQW Granules was established. Forsythoside A standard (lot number: 111810-201708, content 97.2%) was provided by China Institute for Food and Drug Control. Baicalin standard substance (lot number: 110715-202122, content: 95.4%) was provided by China Institute for Food and Drug Control. The precision, stability, repeatability, recovery rate and durability were investigated (See the Supplementary material for details).

2.5. Data collection and evaluation

2.5.1. Primary outcome measure

The patients’ condition was evaluated once every 3 d. The number of patients who had transitioned from moderate to a severe or critical form of the disease within 15 d of admission was recorded, and the ratio of moderate to severe/critical cases was calculated (number of moderate to severe and critical cases/total number of cases × 100%).

2.5.2. Secondary outcome measures

This study prospectively medical records and clinical data for enrolled patients with SARS-CoV-2 infection from Guangzhou Eighth People’s Hospital. All laboratory data were collected at baseline and after medication, including blood cell count. Routine blood tests were performed every 3 d, including white blood cell count (WBC), lymphocyte count (LYM), and percentage of lymphocytes (LYM%), dynamic changes in blood routine tests within 15 d of admission were observed. Blood routine tests were performed using the UniCel® DxH600Coulter® Hematology Analyzer (Beckman Coulter Inc.Brea, California, USA).

Chest CT was performed every 3–5 d depending on the patient’s condition. The scan was performed using a GE 64 row 128-layer OPTIMA CT680. The patient was supine, inspiratory and held his breath. The scan range was from the tip of lung to the bottom of lung with a thickness of 5–6.5 mm, and all 1 mm high-resolution CT reconstruction was performed. Mediastinal window (width of window 300–400 HU, level of window 35–40 HU) and pulmonary window (width of window 1 100−1 300 HU, level of window −700 HU) were selected for observation in PACS. Two radiologists with a professional title of deputy director or above read the films separately, analyze CT findings and score pneumonia, and reach a consensus through consultation if there is any disagreement. A semi-quantitative method was used to score pneumonia: a visual method was used to assess the involvement of individual lobes (Chang et al., 2005) and disease severity was scored using 0–4 points that indicated low to high severity.

The severity of symptoms including fever, cough, phlegm, fatigue, sore throat and poor appetite was scored from 0 to 4 points every 3 d, with 0 indicating no symptoms and 4 indicating the highest severity. The average score of these six symptoms was also calculated for each patient (comprehensive symptom score). The scoring criteria were set depending on the “Guiding Principles for Clinical Trials on New TCM Drugs”.

Chemiluminescence immunoassay (CLIA) was performed to calculate the KL-6 concentration (U/mL) in the samples using a standard curve.

Human serum levels of 71 cytokines were measured using the U-PLEX Biomarker Group 1 (hu) 71-Plex kit and analysed by data extraction using the dedicated DISCOVERY WORKBENCH 4.0 (MSD).

2.6. Statistical analysis

Statistical analyses were conducted using SPSS 27.0 software (SPSS Inc., Chicago, IL, United States). Two-sided tests were used, and P < 0.05 were considered statistically significant. The numerical variables are normally distributed, summarized as mean ± SD and between-group comparison was performed using t-test, the numerical variables are abnormally distributed, the data were expressed as median (Q1, Q3), and between-group comparison was performed using the ranked sum test. The data of the categorical variables are described as numbers and percentages. The chi-square test/Fisher’s exact test was used to compare the gender, history of travel to affected areas, underlying conditions, while the difference in the comprehensive symptom score was analyzed using repeated-measures analysis of variance (ANOVA). The difference in KL-6 levels between the two groups of patients was determined by fitting the data to a generalized linear model were completed using R3.6.2.

3. Results

3.1. General information of enrolled patients

As shown in Table 1, 156 patients (71 males and 85 females) were enrolled. The median age of TJQW + WM group was 52.5 years old and WM group was 48.5. 102 patients have at least one basic disease, such as cardiovascular and cerebrovascular disease, or diabetes. The two treatment groups were comparable in terms of demographic characteristics except gender (P > 0.05).

Table 1.

Characteristic of two patient groups.

Characteristic TJQW + WM group (n = 76) WM group (n = 80) χ2/Z P
Gender n (%)
 Male 27 (35.53) 44 (55) χ2 = 5.96 0.015
 Female 49 (64.47) 36 (45)
Age (years)
median (Q1, Q3)		 52.5 (40.5, 62) 48.5 (33, 62.5) Z = 0.73 0.467
History of travel to affected areas n (%)
 Yes 27 (35.53) 32 (40) χ2 = 0.33 0.565
 No 49 (64.47) 48 (60)
Underlying conditions n (%)
 Yes 53 (69.74) 49 (61.25) χ2 = 1.24 0.265
 No 23 (30.26) 31 (38.75)
Duration from disease onset to detection
median (Q1, Q3)		 5 (3, 7) 4 (2, 6.5) Z = 1.05 0.293
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The Mann-Whitney U test was used for between-group differences in age and duration from disease onset to detection. The chi-square test/Fisher’s exact test was used to compare count data.

3.2. Incidence of severe disease

In the TJQW + WM group, five patients progressed to a severe form of the disease, and one patient became critically ill, with a total of six cases. Hence, the incidence of severe disease in this group was 7.89% (6/76). In the WM group, there were ten severe cases and six critical cases, amounting to a total of 16 cases. The incidence of severe disease in this group was therefore 20% (16/80). The difference in the incidence of severe disease between the two groups was statistically significant (P = 0.025).

3.3. Indicators related to pulmonary inflammation

3.3.1. Dynamic changes in WBC, LYM, LYM%

The results indicated that the WBC counts of both groups were within the normal range. In TJQW + WM group, WBC in day9 and day15 increased compared with Day1, and the difference was statistically significant. In WM group, WBC increased in day6, day9, and day15 compared with day1, and the difference was statistically significant, but there was no statistically significant difference between groups. But that of the WM group showed a decreasing trend in LYM and LYM%, reaching their lowest point on day 12 and gradually recovering thereafter. The LYM and LYM% of the TJQW + WM group decreased slightly in the early stages (days 1−3) after admission and recovered steadily thereafter,the performance is as follows: In TJQW + WM group, compared with day1, LYM in day9, day12, and day15 increased, and the difference was statistically significant. In WM group, compared with day1, LYM% in day6, day9, and day12 decreased, and the difference was statistically significant, the differences in LYM and LYM% between the two groups were most marked on day 12 after admission and were significant (P < 0.05, Table 2).

Table 2.

Dynamic changes in WBC, LYM, LYM%.

Items TJQW + WM group (n = 76) WM group (n = 80) Z/t P value
WBC (× 109)
median (Q1,Q3)
 Day1 5.08 (4.08, 5.84) 4.61 (4.03, 5.60) Z = 0.842 0.478
 Day3 4.82 (3.62, 6.31) 5.09 (3.69, 6.80) Z = 0.598 0.867
 Day6 5.46 (4.33, 6.30) 5.50 (5.51, 7.17)** Z = 1.007 0.262
 Day9 5.30 (4.20, 7.18)* 5.27 (4.55, 6.71)** Z = 0.696 0.718
 Day12 5.35 (4.70, 6.44) 5.45 (4.50, 6.52) Z = 0.673 0.755
 Day15 5.26 (3.91, 8.00)** 5.73 (4.57, 6.66)* Z = 0.633 0.818
LYM (× 109)
 Day1 1.37 (1.11, 2.03) 1.36 (1.07, 1.84) Z = 0.447 0.988
 Day3 1.42 (1.11, 1.81) 1.37 (1.08, 2.08) Z = 0.817 0.184
 Day6 1.62 (1.34, 1.99) 1.49 (1.09, 2.16) Z = 1.092 0.184
 Day9 1.44 (0.92, 2.30)* 1.59 (1.14, 1.94) Z = 1.189 0.119
 Day12 1.70 ± 0.44* 1.34 ± 0.48 t =  − 3.497 0.001
 Day15 1.64 ± 0.64* 1.52 ± 0.58 t =  − 0.638 0.527
LYM (%)
mean ± SD
 Day1 30.87 ± 10.17 32.40 ± 10.43 t = 0.742 0.460
 Day3 31.84 ± 11.02 29.68 ± 14.27 t =  − 0.692 0.491
 Day6 32.06 ± 10.78 28.33 ± 13.37** t =  − 1.704 0.091
 Day9 30.63 ± 11.72 27.64 ± 12.70* t =  − 0.986 0.327
 Day12 32.20 ± 8.18 25.23 ± 10.40* t =  − 3.396 0.001
 Day15 29.16 ± 10.47 29.24 ± 13.99 t = 0.022 0.983
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Compared with Day 1 in the same group, *P < 0.05, **P < 0.01.

3.3.2. Dynamic changes in CT scores

The CT score of the TJQW + WM group peaked on day 3 after admission and gradually decreased thereafter. The WM group showed a wave-like rebound, after which the CT score decreased slightly at days 6–9 after admission but increased thereafter. CT scores were significantly higher in day3 and day6 compared with Day1 in both groups (P < 0.05). The differences in CT score on day 12 and day 15 were significant between the two groups (P < 0.05) as shown in Table 3.

Table 3.

Dynamic changes in CT scores.

Group Day1 Day3 Day6 Day9 Day12 Day15
TJQW + WM group 1.95 ± 0.99 2.15 ± 0.87* 2.10 ± 0.84* 2.08 ± 0.91 1.87 ± 0.84 1.84 ± 0.77
WM group 2.01 ± 1.08 2.22 ± 0.97** 2.18 ± 1.09* 2.10 ± 1.10 2.26 ± 0.85** 2.33 ± 0.92**
t 0.392 0.433 0.472 0.072 2.047 2.279
P value 0.696 0.665 0.638 0.943 0.044 0.026
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Compared with Day 1 in the same group, *P < 0.05, **P < 0.01.

3.4. Serum KL-6 levels

A comparison of KL-6 levels between the two groups was achieved by fitting the data to a generalized linear model. After controlling for the effects of the duration from disease onset to detection, the results indicated that the KL-6 levels of the TJQW + WM group were lower than those observed in the WM group (t = 3.703, P < 0.01, Fig. 1).

Fig. 1.

Fig. 1

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Dynamic changes in serum KL-6 levels (KL-6: Krebs von den Lungen 6).

3.5. Clinical symptom score

Repeated-measures ANOVA was performed on the two groups for the six most common SARS-CoV-2 infection symptoms including fever, fatigue, cough, phlegm, poor appetite and sore throat on days 1, 3, 6, 9, 12, and 15 after the treatment began. The results indicated that compared with day1, both groups at different time points showed varying degrees of improvement in the six most common (P < 0.05) the differences between the two groups for these six symptoms were insignificant (all P > 0.05, Table 4). Further analysis was performed on the comprehensive score of the six symptoms, compared with day1, both groups at different time points showed varying degrees of improvement in composite scores (P < 0.05), which showed that the between-group difference was also insignificant (F = 0.031, P = 0.871). However, there was an interaction effect between treatment plan and treatment duration, with significant differences in the degree of change at each time point for the comprehensive scores (F = 6.502, P < 0.01, Table 4).

Table 4.

Clinical symptom score.

Items TJQW + WM group (n = 76) WM group (n = 80) Value of statistics P value
F = 0.031 0.871
Fever
 Day1 1.00 (0.00, 1.50) 0.00 (0.00, 1.00) −2.152 0.031
 Day3 0.00 (0.00, 1.00)** 0.00 (0.00, 1.00) −0.078 0.938
 Day6 1.00 (0.00, 1.50)** 0.00 (0.00, 1.00)** −1.179 0.238
 Day9 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −0.417 0.677
 Day12 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −1.814 0.070
 Day15 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −1.422 0.155
Fatigue
 Day1 1.00 (0.00, 1.50) 0.00 (0.00, 1.00) −0.113 0.910
 Day3 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −0.118 0.906
 Day6 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −1.606 0.108
 Day9 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −1.431 0.153
 Day12 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −0.646 0.518
 Day15 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −0.061 0.951
Cough
 Day1 1.00 (0.50, 1.00) 1.00 (0.00, 1.00) −1.134 0.257
 Day3 1.00 (0.00, 1.00)** 1.00 (0.00, 1.00)* −0.413 0.680
 Day6 0.00 (0.00, 1.00)** 1.00 (0.00, 1.00)* −1.223 0.221
 Day9 0.00 (0.00, 1.00)** 0.00 (0.00, 1.00)** −1.163 0.245
 Day12 0.00 (0.00, 1.00)** 0.00 (0.00, 1.00)** −0.011 0.991
 Day15 0.00 (0.00, 1.00)** 0.00 (0.00, 1.00)* −1.063 0.288
Phlegm
 Day1 0.00 (0.00, 1.00) 0.00 (0.00, 1.00) −1.134 0.257
 Day3 0.00 (0.00, 1.00) 0.00 (0.00, 1.00) −1.069 0.285
 Day6 0.00 (0.00, 1.00)* 0.00 (0.00, 1.00) −0.242 0.808
 Day9 0.00 (0.00, 0.5)* 0.00 (0.00, 0.00)* −0.772 0.440
 Day12 0.00 (0.00, 0.00) 0.00 (0.00, 0.00)** −1.277 0.201
 Day15 0.00 (0.00, 0.00)* 0.00 (0.00, 0.00) −0.533 0.594
Poor appetite
 Day1 0.00 (0.00, 1.00) 0.00 (0.00, 0.00) −3.532 0.000
 Day3 0.00 (0.00, 1.00) 0.00 (0.00, 1.00)** −0.276 0.783
 Day6 0.00 (0.00, 1.00) 0.00 (0.00, 1.00)** −1.383 0.167
 Day9 0.00 (0.00, 0.00)* 0.00 (0.00, 1.00) −1.893 0.058
 Day12 0.00 (0.00, 0.00)** 0.00 (0.00, 1.00) −3.762 0.000
 Day15 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00) −2.149 0.032
Sore throat
 Day1 0.00 (0.00, 1.00) 0.00 (0.00, 0.00) −3.506 0.000
 Day3 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)* −1.609 0.108
 Day6 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)* −0.977 0.329
 Day9 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −1.419 0.156
 Day12 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** 0.000 1.000
 Day15 0.00 (0.00, 0.00) 0.00 (0.00, 0.00)* −1.059 0.290
Comprehensive symptom scores F = 6.502 P < 0.01
 Day1 1.00 (0.00, 1.00) 0.00 (0.00, 1.00) −4.410 0.000
 Day3 0.00 (0.00, 1.00)** 0.00 (0.00, 1.00)** −0.421 0.674
 Day6 0.00 (0.00, 0.00)** 0.00 (0.00, 1.00)** 0.915 0.373
 Day9 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −1.214 0.225
 Day12 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** −1.620 0.105
 Day15 0.00 (0.00, 0.00)** 0.00 (0.00, 0.00)** 0.754 0.621
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Compared with Day 1 in the same group, *P < 0.05, **P < 0.01.

3.6. Serum cytokine expression

Overall, there was a positive trend in the changes of cytokines after treatment in the TJQW + WM group. Among the thymic stromal lymphopoietin (TSLP) levels after treatment, the difference was statistically significant (P = 0.004) in TJQW + WM group. In WM group, thrombopoietin (TPO) decreased after treatment compared with that before treatment (P < 0.05), the level of TPO after treatment was significantly lower in the WM group than in the TJQW + WM group, and there was a statistically significant difference (P = 0.026). After treatment, the trend of interleukin-3 (IL-3) level was significantly lower in the TJQW + WM group than in the WM group, and the difference was statistically significant (P = 0.002). TJQW + WM group, interferon-α (IFN-α) after treatment was lower than that before treatment (P < 0.05), IFN-α level after treatment was significantly lower in TJQW + WM group than WM group, with a statistically significant difference (P = 0.009). The level of IL-1β after treatment was statistically different (P = 0.028) decreased better in TJQW + WM group than in WM group. There was a statistically significant difference in the level of IL-4 after treatment (P = 0.020), which was significantly higher in the TJQW + WM group than in the WM group (Table 5).

Table 5.

Comparison of serum cytokines between two groups (pg/mL) [median (Q1, Q3)].

TJQW + WM group (n = 20) WM group (n = 20) Z P value
TSLP
 Pre-treatment 4.03 (2.76, 5.89) 5.63 (3.33, 9.25) 1.109 0.267
 Post-treatment 3.33 (2.15, 6.54) 7.42 (3.41, 11.77) 2.056 0.004
TPO
 Pre-treatment 89.68 (47.08, 185.54) 65.11 (40.54, 205) −0.555 0.583
 Post-treatment 106.58 (67.64, 126.78) 65.24 (22.58, 91.85)* −2.205 0.026
IL-1β
 Pre-treatment 0.37 (0.22, 1.02) 0.58 (0.29, 1) 1.137 0.265
 Post-treatment 0.25 (0.13, 0.60) 0.80 (0.34, 1.24) 2.193 0.028
IL-3
 Pre-treatment 18.03 (14.77, 21.94) 18.95 (16.67, 27.23) 1.286 0.201
 Post-treatment 17.64 (15.09, 19.33) 20.32 (18.26, 27.12) 3.003 0.002
IFN-α
 Pre-treatment 4.44 (3.06, 4.94) 4.6 (3.27, 7.86) 1.191 0.242
 Post-treatment 3.29 (2.76, 3.83)* 4.63 (3.31, 6.75) 2.572 0.009
IL-4
 Pre-treatment 0.18 (0.07, 0.27) 0.10 (0.04, 0.16) 1.151 0.253
 Post-treatment 0.21 (0.09, 0.45) 0.08 (0.03, 0.12) 2.315 0.020
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Compared with Pre-treatment in the same group, *P < 0.05.

3.7. Safety and adverse events

There were no serious adverse events and no adverse events that were associated with cessation of the trial regimen.

4. Discussion

Several therapeutic approaches have been developed to relieve symptom and reduce the probability of progression into severe or critical illness. These mainly include antivirals (remdesivir, nirmatrelvir-ritonavir, monulpiravir) (Arbel et al., 2022, Gottlieb et al., 2022, Jayk Bernal et al., 2022), immunodulatory therapy (corticosteroids, IL-6 inhibitors, Janus kinase inhibitors) (Marconi et al., 2021) monoclonal antibodies (tixagavimab-cilgavimab, sotrovimab, tocilizumab) (Gordon et al., 2021; Gupta et al., 2021, Levin et al., 2022) and anti-inflammatory drugs (baricitinib, tofacitinib) (Guimarães et al., 2021, Kalil et al., 2021). For the majority of individuals with mild to moderate illnesses who are treated at home or in the community, there remains a paucity of less expensive medications that can improve symptoms. This study found that TJQW Granules could diminish the progression to severe disease, promote lymphocyte recovery, reduce pulmonary inflammation, and alleviate pulmonary fibrosis.

The typical clinical course of SARS-CoV-2 infection is divided into the early stage, progression stage, and recovery stage. The early-stage generally refers to 1–7 d from disease onset, while the progression stage mostly occurs in 8–14 d, but it maybe longer for individual patients. Studies have shown that after the acute stage, approximately two-thirds of patients will improve gradually, with their body temperatures returning to normal and the disappearance of pulmonary lesions. The remaining one-third of patients will continue to experience fever, cough, and other symptoms of viral infection, while the condition of a minor few may worsen even further. Their body temperatures will rise above 39 °C within 3–5 d, showing persistent fever that is often accompanied by an obvious dry cough or a productive cough with a small amount of sputum. A few cases may show hemoptysis, and coughing may aggravate dyspnea. Therefore, in this study, the case inclusion criteria were defined as moderate SARS-CoV-2 infection along with hospital admission within 10 d of disease onset and immediate administered TJQW Granules after admission, to better observe the impact of this drug on patients with moderate SARS-CoV-2 infection.

Our findings indicate that TJQW Granules could significantly reduce the incidence of a severe form of the disease. By observing the dynamic changes in routine blood tests, it was found that both groups of patients showed relatively low WBC and LYM counts at admission. The WM group showed a more significant decline in LYM 1–2 weeks after admission, reaching its lowest level at day 12, whereas the LYM count of the TJQW + WM group did not decrease, but instead showed a trend of gradual increase and recovery. The difference in LYM count between the two groups was most significant at day 12. A study has reported that 83.2% of SARS-CoV-2 infected patients showed lymphopenia, and 33.7% showed leukopenia (Guan et al., 2020). A possible reason for this may be that once the body has been infected by SARS-CoV-2, it will initiate cellular immunity and hence infect immune cells in the process of eliminating the virus, thus causing significant decline in WBC and LYM count (Mazzoni, Salvati, Maggi, Annunziato, & Cosmi, 2021). Studies conducted in China and abroad have also found that patients with low LYM at the initial stage of the disease tend to have a poor prognosis, while the peripheral blood LYM count of severely ill patients showed a progressive decline (Wang et al., 2020). Study shows that WBC, LYM, and other indicators were directly associated with viral load and pulmonary damage. The significant LYM reduction in severely ill patients is closely related to the overactivation of T lymphocytes in the process of cytokine storms, accompanied by severe damage to immune function (Guan et al., 2020, Huang et al., 2020, Huang and Pranata, 2020, Lee et al., 2021, Liao et al., 2020). This study speculated that the underlying mechanism of TJQW Granules in significantly reducing the incidence of severe disease may be related to its regulation of the immune system (Brendler et al., 2021, Maggi et al., 2020). TJQW Granules encompasses the use of heat-clearing herbs such as Forsythiae Fructus, Lonicerae Japonicae Flos, Scutellariae Radix, and Isatidis Folium. From the perspective of modern pharmacological research, the herbs mentioned above not only inhibit respiratory viruses to a certain extent but also suppress the excessive immune-inflammatory response, reduce the levels of Toll-like receptors and inflammatory chemokines, such as IL-6, IL-17 and monocyte chemotactic-1 (MCP-1) in pulmonary and intestinal tissues, and decrease tumor necrosis factor (TNF-α) levels and downregulate nuclear factor kappa-B (NF-κB) expression to reduce pulmonary inflammatory damage, thereby alleviating inflammatory damage (Huang et al., 2021, Liu et al., 2021). The formula also includes herbs such as Astragali Radix and Pseudostellariae Radix, which can promote IFN immune activation, increase cellular immunity to enhance immune response, and prevent persistent viral infection (Chen et al., 2020a, Chen et al., 2020b, Fu et al., 2014, Ye et al., 2021).

This study also found that the CT scores of patients in the TJQW + WM group began to decrease continuously after the administration of TJQW Granules, whereas that of the WM group showed a wave-like trend of increase, which indicates that TJQW Granules could significantly promote the reduction of pulmonary inflammation. The CT scores of the WM group continued to increase on days 12–15 during the disease, which may be related to the higher number of severely and critically ill patients in this stage, which affected the CT scores of the entire group. In addition, this study also found that the KL-6 levels of the TCM + WM group were significantly lower than the levels observed in the WM group. KL-6 is a specific marker for type II alveolar epithelial cells, which not only indicates the inflammatory damage inflicted on these cells but also promotes the proliferation and migration of fibroblasts, thereby influencing the onset and development of fibrosis (Benyamine et al., 2018, Hirasawa et al., 1997, Yokoyama et al., 2006). Therefore, it can also indicate the extent to which fibrosis has occurred and progressed. Several recent studies have reported that high KL-6 expression levels may be related to viral pneumonia, drug-induced interstitial pneumonia, tumors, and other diseases (Kawasaki et al., 2009, Kuwana et al., 2016, Lee et al., 2019, Salazar et al., 2018). Therefore, the changes in the CT scores and KL-6 levels of the TJQW + WM group signify that TJQW Granules has effectively reduced the inflammatory damage and fibrosis in SARS-CoV-2 infection. Our research team has found that the use of mucolytics is the key to alleviate diseases where in the lungs are the primary lesion site. Hence, large number of mucolytic herbs were used in this formula. The autopsy of SARS-CoV-2 infection cases also revealed that the small airways were extensively blocked by sticky and cold phlegm (Li and Tang, 2021, Yao et al., 2021). Recently, an autopsy analysis (National Health Commission of the People's Republic of China and National Administration of Traditional Chinese Medicine, 2020) on the patients who died of coronavirus due to respiratory distress and hypoxemia were found that large number of viscous secretions exudate in the air sacs, white foamy mucus in the airway, and gelatinous mucus adhering in the bronchial lumen. The obstruction of the small air tract (lack of goblet cells) is the most prominent feature of SARS-CoV-2 infection, which leads to infection, ventilation dysfunction, acute respiratory distress syndrome (ARDS), and uncorrected hypoxemia. Overproduction of mucin interacts with platelets or forms aggregates, which may lead to airway blockage (Bikdeli et al., 2020, Deshpande, 2020, Lax et al., 2020). Therefore, the abnormal secretion of airway mucus was one of the major causes of death in critical patients, this study speculated that core TCM of the phlegm-eliminating recipe is a potential therapy for mucus hypersecretion caused by SARS-CoV-2 infection (Zhang et al., 2020).The herbs of TJQW Granules such as Poria, Fritillariae Cirrhosae Bulbus, Bulbus Fritillariae Cirrhosae, Scutellariae Radix have effects on dissolving phlegm, resolving turbidness and dispelling dampness (Chen et al., 2020a, Chen et al., 2020b, Shu et al., 2020, Wu et al., 2018).

In addition, the results of this study also showed that compared with the WM group, the TJQW + WM group showed significant improvements in symptoms such as fever, cough, and phlegm, 3 d after receiving TJQW Granules treatment, while fatigue also improved markedly by day 6. This suggests that TJQW Granules was able to rapidly alleviate the clinical symptoms of patients. During the period of drug administration, apart from a few patients who experienced gastrointestinal reactions such as nausea, vomiting, and increased stool frequency, no other adverse reactions or adverse events occurred, thus demonstrating the safety of the treatment.

Finally, it was found that TJQW Granules can reduce the level of pro-inflammatory factors: TSLP, IL-3, IFN-α, IL-1β, and can elevate the level of anti-inflammatory factor IL-4, avoiding excessive inflammatory response caused by cytokine stimulation of the immune system, improving the elevation of some of the cytokines, and preventing cytokine storms to a certain degree, and alleviating the inflammatory damage of the organism. In the course of disease progression, SARS-CoV-2 infection may induce a cytokine storm, which frequently results in inflammation, lung injury, and ultimately causes ARDS and even pulmonary fibrosis. In such instances, antiviral treatment alone may not be sufficient to effectively combat the viral infection. TCM exhibits multi-component and multi-target characteristics, and can exert antiviral effects by directly intervening with the viral infection process, while also acting to activate and support the body’s immune system. This illustrates the advantages of TCM in the prevention and treatment of SARS-CoV-2 infection.

This study had several limitations. First, it is limited by the type of study and sample size. The gender difference in the TJQW + WM group was significant. Second, due to the unique and unknown nature of this disease, it is difficult to achieve a pure TCM treatment and giving the exact same treatment regimen to all patients in the WM group. Third, a randomized controlled trial could not be performed. Fourth, an in-depth investigation was not performed on the mechanism of action underlying the reduction in the incidence of a severe form of the disease by TJQW Granules. In follow-up, we will actively conduct a randomised controlled trial of cases and collect a series of samples to test for viral load, antibodies and cytokine markers to explore in greater depth the mechanisms and effective targets of TJQW Granules in reducing the progression of the disease to severe illness.

5. Conclusions

TJQW Granules has shown satisfactory results and good completeness in significantly reducing disease severity, blocking disease progression, promoting the absorption of pulmonary inflammation, and rapidly improving clinical symptoms among patients with moderate SARS-CoV-2 infection. It is a beneficial attempt and exploration on the use of TCM for the early intervention of respiratory infectious diseases and provides an effective drug alternative for coping with global outbreaks.

CRediT authorship contribution statement

Qihua Xu: Data curation, Formal analysis, Visualization, Writing – original draft. Xinyue Zhang: Data curation. Sanqi Huang: Data curation. Linghua Li: Methodology, Supervision. Feng Li: Methodology, Supervision. Wei Liu: Formal analysis, Data curation. Kunzhou Ling: Resources, Investigation. Jialong Guan: Resources, Investigation. Xinghua Tan: Conceptualization, Methodology, Project administration, Supervision, Funding acquisition. Luping Lin: Conceptualization, Methodology, Project administration, Supervision, Funding acquisition.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

Authors thank for the support of emergency project for clinical research on the prevention and treatment of COVID-19 in traditional Chinese medicine of the Traditional Chinese Medicine Bureau of Guangdong Province (No. 2020ZYYJ01) and Emergency project for major public health incidents of the Guangdong Science and Technology Department (No. 2020B111115003). The authors gratefully acknowledge all patients and health-care workers in the Guangzhou Eighth People’s Hospital. This study also acknowledge Professor Xingyu Zheng of Fujian Provincial Hospital and the research team headed by Professor Xiaoling Chi of Guangdong Hospital of Traditional Chinese Medicine for their guidance and assistance in this project.

Footnotes

Appendix A

Supplementary data to this article can be found online at https://doi.org/10.1016/j.chmed.2026.02.016.

Contributor Information

Xinghua Tan, Email: gz8htxh@126.com.

Luping Lin, Email: gz8hlinluping@126.com.

Appendix A. Supplementary material

The following are the Supplementary data to this article:

Supplementary Data 1
mmc1.docx (324.3KB, docx)

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