Management of asymptomatic to mild COVID-19 patients with Cheongpebaedok-tang on the telemedical basis: A retrospective observational case series

Article information

J Korean Med. 2023;44(4):41-58

Publication date (electronic) : 2023 December 1

doi : https://doi.org/10.13048/jkm.23046

Sung-Woo Kang^1,†, Kwan-Il Kim^1,2,†, Mideok Song³, Jinhwan Roh⁴, Namhun Cho⁵, Heung Ko⁶, Sung-Se Son⁷, Minjeong Jeong⁸, Jun-Yong Choi⁹, Ojin Kwon¹⁰, Seojung Ha^2,11, Hee-Jae Jung^1,2,, Beom-Joon Lee^1,2,

¹Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee University

²Department of Internal Medicine (Pulmonary & Allergy System), Kyung Hee University Medical Center

³Kyunghee Korean Medicine clinic

⁴Seoul Kyunghee Clinic

⁵Wondang Kyunghee Korean medical clinic

⁶Department Korean Internal Medicine, College of Korean Medicine, Semyung University

⁷Department of Acupuncture & Moxibustion, CHA Bundang Medical Center, CHA University

⁸Department of Pediatrics, College of Korean Medicine, Woosuk University

⁹Department of Korean Internal Medicine, School of Korean Medicine & Korean Medicine Hospital of Pusan National University

¹⁰KM Science Research Division, Korea Institute of Oriental Medicine

¹¹Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University

Correspondence to: Hee-Jae Jung, Beom-Joon Lee, Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea, Tel: +82-2-958-9146, Fax: +82-2-961-9505, E-mail: hanfish@khmc.or.kr (HJ), franchisjun@naver.com (BL)

^†

The authors contributed equally to this work.

Received 2023 October 5; Revised 2023 November 14; Accepted 2023 November 15.

Abstract

Introduction

Coronavirus disease 2019 (COVID-19) started spreading in Wuhan City, Hubei Province, China at the end of 2019 and was declared a global pandemic by the World Health Organization on March 11, 2020.1) After the first confirmed COVID-19 case in the Daegu region of Gyeongsangbuk-do on February 18, 2020, the number of patients with COVID-19 exponentially increased in the Republic of Korea, resulting in an epidemic with 5,000 confirmed cases by March 7, 2020. The Korea Centers for Disease Control and Prevention operated the “Regional Risk Stratification and Triage System” in Daegu. The severity class was divided into asymptomatic, mild, moderate, severe, and critical by doctors who interviewed patients by phone (Table 1).2)

Table 1

COVID-19 Brief Severity Scoring System of Daegu

The Association of Korean Medicine (AKOM) operates the telemedicine center of Korean medicine, targeting patients with asymptomatic to mild and moderate COVID-19. The AKOM has published telemedicine guidelines for COVID-19 management which present a treatment algorithm3) based on previously published Korean medicine and traditional Chinese medicine treatment guidelines, such as those in COVID-19 Korean Medicine Clinical Guidance (2nd ed.)4), the Clinical Guidelines on COVID-19 Korean Medicine5), and the Diagnosis and Treatment Protocol for COVID-19 (Trial Version 7).6) An average of 15 doctors provided treatment at the telemedicine center for an average of 192 patients per day from March 3, 2020 to April 12, 2020; as of April 13, 2020 the proportion of patients using telemedicine centers among all COVID-19 confirmed cases was 16.53% of all patients in Korea.7)

Cheongpebaedok-tang (Qingfei Paidu decoction in China) is the main herbal medicine recommended for the treatment of all stages of COVID-19 by the National Health Commission of the People’s Republic of China.8) It is one of the most effective herbal medicines for treating COVID-19 and is strongly recommended by most traditional Korean medicine guidelines.4–6) Therefore, Cheongpebaedok-tang was recommended as a basic prescription for patients with confirmed COVID-19 in the telemedicine guidelines.3) This study investigated the efficacy and safety of telemedical management using Korean medicine centered on Cheongpebaedok-tang for treating patients with asymptomatic to mild COVID-19.

Methods

3. COVID-19-related symptom severity

At the first and last treatment sessions, a Korean medicine doctor evaluated COVID-19 -related symptoms to determine the severity. The evaluation tool consists of 15 symptom items, each of which was evaluated as none, mild, moderate, or severe (Table 2).

Table 2

COVID-19-related Symptom Severity

Results

1. Patient characteristics

Twenty-seven patients were included in this analysis (Figure 1). The mean patient age was 48.7 ± 2.3 years. The comorbidities included hypertension in four patients (14.8%), gastritis in three patients (11.1%), angina in two patients (7.4%), and hyperlipidemia, cancer, and chronic bronchitis in one patient each (3.7%). Two (7.4%) patients had a history of smoking. The initial treatment was no treatment in 19 patients (70.4%), over-the-counter cold medicines in six patients (22.2%), non-steroidal anti-inflammatory drugs in two patients (7.4%), and antibiotics in one patient (3.7%). During the initial evaluation of patients, radiological evaluation was not performed in 20 patients (74.1%). Among seven patients who underwent chest radiography, six patients (22.2%) had normal findings, and mild pneumonia was suspected in one patient (3.7%). During the initial evaluation, serological evaluation was not performed in 26 patients (96.3%), and one serologically-evaluated patient showed values that were within the normal reference range (Table 3).

Fig. 1

Flowchart of patients with confirmed COVID-19 in the retrospective observational study

Table 3

Baseline Demographic and Clinical Characteristics of Patients

2. Duration of related indicators in patients with COVID-19

The duration of change from positive to two negative results on the polymerase chain reaction (PCR) test was 30.8 ± 2.6 days. When classified according to the type of isolation, results revealed 18.4 ± 2.2 days in five patients who were in home isolation (19%) and 33.6 ± 2.9 days in 22 patients who were in facility isolation (81%). In patients who were isolated at home, 1.2 ± 0.7 days passed from self-isolation to the onset of symptoms, 4.6 ± 1.6 days from self-isolation to confirmation of COVID-19 on the PCR test, and 18.4 ± 2.2 days from confirmation of two negative results on the PCR test. In patients who were isolated in facilities, 1.5 ± 1.4 days passed from onset of symptoms to self-isolation, 6.7 ± 1.5 days from self-isolation to confirmation of COVID-19 on the PCR test, 4.7 ± 1.3 days from confirmation to isolation in facilities, and 28.9 ± 3.0 days from facility isolation to two negative results on PCR tests (Table 4, Figures 2 and 3).

Table 4

Duration of Related Indicators

Fig. 2

Duration of related indicators in patients in home isolation (n = 5)

Fig. 3

Duration of related indicators in patients in facility isolation (n = 22)

4. Concomitant medication with Cheongpebaedok-tang

Fourteen patients (51.9%) self-administered other herbal medicines concomitantly, including four patients (14.8%) taking Gwakhyangjeonggi-san, four patients (14.8%) taking Kyungokgo, two patients (7.4%) taking Mokhyanggongjindan, and one patient each (3.7%) taking Hyunggaeyunkyo-tang, Jaumbope-tang, Sohamhyung-tang, and Yikkibope -tang (Table 5).

Table 5

Concomitant Medication with Cheongpebaedok-tang

5. Herbal medicine in the convalescent period

Regarding the herbal medicine used in the convalescent period, Kyungokgo was the most commonly used medicine in 11 patients (40.7%), followed by Jaumbope-tang in seven patients (25.9%), Yikkibope-tang in six patients (22.2%), Cheongpe-kyungokgo in four patients (14.8%), Mokhyanggongjindan in four patients (14.8%), Eunkyo-san in three patients (11.1%), Hyangsayukkunja-tang in two patients (7.4%), Gamikuibi-tang in two patients (7.4%), and Sohamhyung-tang, Yunkyopaedok-san, Gwakhyangjeonggi-san, and Sochungryong-tang in one patient each (3.7%) (Table 6).

Table 6

Herbal Medicine in the Convalescent Period

6. Change in the severity of COVID-19-related symptoms after treatment using Korean medicine

The reported patient symptoms during the treatment period were sputum in 15 patients (55.6%), cough in 14 patients (51.9%), sore throat in 11 patients (40.7%), chest discomfort in nine patients (33.3%), dry mouth in eight patients (29.6%), nasal congestion in eight patients (29.6%), rhinorrhea in six patients (22.2%), anorexia in six patients (22.2%), headache or dizziness in six patients (22.2%), fatigue in four patients (14.8%), chills in three patients (11.1%), myalgia in three patients (11.1%), diarrhea in three patients (11.1%), chest pain in three patients (11.1%), and nausea, mild fever, and anosmia in one patient each (3.7%). The changes in symptom severity before and after treatment using Korean medicine are shown in Figure 4.

Fig. 4

Severity of COVID-19-related Symptoms Before and After Treatment with Korean Medicine

7. Changes in COVID-19-related symptoms during the chronic phase

The chronic phase symptoms observed six months after the end of treatment were investigated through telephone follow up. The chronic phase symptoms included fatigue in 14 patients (51.9%), ocular symptoms (red eyes, dry eyes) in ten patients (37.0%), sore throat in six patients (22.2%), anosmia in five patients (18.5%), headache or dizziness in four patients (14.8%), rhinitis in three patients (11.1%), cough in three patients (11.1%), dyspnea in two patients (7.4%), dyspepsia or anorexia in three patients (11.1%), myalgia in two patients (7.4%), sputum in two patients (7.4%), chest discomfort in two patients (7.4%), dysgeusia in two patients (7.4%), and hot flash, dry mouth, and memory impairment in one patient each (3.7%) (Figure 5).

Fig. 5

Comparison of COVID-19-related Symptoms During Acute and Chronic Phases

Discussion

Cheongpebaedok-tang, the main focus of this study, is a prescription for treating the Korean medicine consideration of the pathological mechanism of COVID-19, which appears as cold, dampness, heat, toxin, and deficiency. Cheongpebaedok-tang is a combination n of several Korean medicine prescriptions.9) Animal studies have shown that Cheongpebaedok-tang has antiviral, anti-inflammatory, and metabolic programming effects against COVID-19.10,11) In addition, according to a systematic review and meta-analysis investigating randomized controlled trials, non-randomized trials, cohort studies, and pre-post studies, Cheongpebaedok-tang reduced the nucleic acid conversion time; shortened the hospitalization period; shortened the fever, cough, and chest computed tomography symptom improvement period; reduced the traditional Chinese medicine symptom score; and improved laboratory test biomarkers, including white blood cells, aspartate aminotransferase, and C-reactive protein.12) Based on the above evidence, Cheongpebaedok-tang was adopted as a basic prescription for asymptomatic or mild confirmed cases of COVID-19 in the Korean telemedicine guidelines,3) and was the second most commonly used prescription in the telemedicine center of Korean medicine.13)

According to our results, treatment using Cheongpebaedok-tang reduced the severity of most COVID-19 symptoms. The number of patients complaining of chills, cough, sputum, sore throat, nausea, diarrhea, dry mouth, stuffy nose, rhinorrhea, chest discomfort, chest pain, headache, and anorexia decreased after treatment.

According to a retrospective multicenter cohort study in a comparable timeframe, among 7,057 patients diagnosed with COVID-19 from February 18 to July 10, 2020 in Daegu, 2,162 (30.6%) were asymptomatic, 3,305 (46.8%) had mild disease, and 985 (14.0%) had moderate disease, totaling 6,452 (91.4%). Regarding isolation methods, 202 patients (2.9%) were isolated at home and 2,784 (39.5%) were isolated at a facility. Among the 2,254 patients for whom clinical information could be confirmed, 664 patients (29.5%) had mild symptoms and 985 patients (43.7%) had moderate symptoms, totaling 1,649 patients (73.2%). Cough (38.0%), sputum (29.6%), fever (18.5%), myalgia (17.1%), headache (16.8%), diarrhea (11.4%), sore throat (10.4%), and rhinorrhea (8.4%) were the most common symptoms. For survivors, the mean time from isolation to release was 33 days (interquartile range, 24.0–46.0).14) In a similar period, from January 22, 2020, to May 30, 2020, a survey of 370,000 COVID-19 cases reported to the United States Centers for Disease Control and Prevention revealed that the most common initial symptoms were cough (50.3%), fever (43.1%), myalgia (36.1%), headache (34.4%), shortness of breath (28.5%), and sore throat (20.0%),15) similar to the current study and the retrospective multicenter cohort study. Compared with contemporaneous retrospective studies, patients who were prescribed Cheongpebaedok-tang via telemedicine showed similar results for sputum, cough, sore throat, and rhinorrhea symptoms.

The differences between this study and previous studies are as follows. First, dyspnea was reported less frequently in this study than that reported in previous studies.14,15) Unlike previous studies, only asymptomatic to mild patients were included in the current study; patients with respiratory distress were not included because their severity of illness was evaluated as higher than that of those patients who did not have respiratory distress. Second, dry cough is a common pattern in patients with COVID-19.16) However, our study patients in the acute phase mainly complained of a productive cough with sputum. The different cough patterns may be interpreted as the initial infection being mainly inflammation confined to the nasal passages, throat, and upper respiratory tract in patients with mild symptoms during the acute phase.

Our study revealed both similarities and differences in persistent symptoms from those reported in previous studies. A previous study conducted in Italy, including patients during a similar period from April 21 to May 29, 2020, showed that fatigue was the most common complaint among patients with COVID-19, even in patients in the acute phase.17) Conversely, our study and a study conducted in Daegu14) revealed that fatigue was uncommon in the acute phase. However, fatigue was the only symptom that increased after Korean telemedicine treatment compared to that before treatment, and fatigue emerged as a common symptom in the chronic phase. In addition, ocular symptoms were commonly reported in the present study. Post-COVID-19 fatigue is the most common sequela reported in clinical studies.17–21) Various causes have been suggested, including central factors, such as changes in neurotransmitter levels due to the invasion of the central nervous system by the coronavirus, nerve excitability and inflammation, psychological factors such as fear due to isolation, and peripheral factors, such as skeletal muscle myopathies.22) Symptoms such as conjunctival congestion and dry eye were previously reported in patients with COVID-19,23) and as sequelae, decreased near vision, burning sensation, foreign body sensation, and redness were reported.24) Although the Korean medicine telemedicine guideline suggests convalescent prescriptions for managing sequelae at the last treatment, the current study cannot provide a comprehensive review of the improvement in symptoms after the recovery phase because the treatment was terminated at the same time as the administration of the convalescent prescription. Several studies have purported that herbal medicines are effective in improving symptoms, lung function, and imaging in mild cases and in the management of COVID-19 sequelae.25,26) Given that clinical trials have been registered and are recruiting,27,28) it is expected that additional well-designed large-scale clinical studies will be published in the near future.

The results of this study indicate that telemedicine in Korean medicine is safe. There was no worsening of the severity of COVID-19 during the Korean medicine telemedicine treatment period. A research conducted in March 2020 in Daegu, focusing on asymptomatic and mild COVID-19 cases at community treatment centers, reported that 3% of the participants required hospitalization primarily due to the exacerbation of respiratory symptoms or abnormalities identified in chest radiographs.29) Despite the similarities in recruitment timeframe and symptom severity, none of the patients included in this study were admitted to a hospital due to worsening COVID-19 symptoms. This may be related to the effect of Cheongpebaedok-tang on the decrease in the hospitalization period and symptom relief observed in previous studies.12) Only minor side effects of Cheongpebaedok-tang were investigated in the current study, including heart palpitations, insomnia, dizziness, and diarrhea. Considering that the symptoms improved when the prescription was changed to Cheongpebaedok-tang 2 (Cheongpebaedok-tang without ephedra) or when the number of prescription doses was reduced, the symptoms that improved were consistent with the previously reported side effects of ephedra.30–32) Therefore, Cheongpebaedok-tang appears to be safe, following the recommendation that Cheongpebaedok-tang 2 should be used when side effects are expected.

This study has several limitations. First, as this study took the form of a retrospective case series study through review of medical records, the effect of Cheongpebaedok-tang on the improvement of the patients could only be evaluated using symptoms and not objective indicators such as imaging and blood tests. Fully understanding the effects of Cheongpebaedok -tang in detail will require randomized controlled studies using objective outcome measures such as hospitalization rate, mortality, and recovery period. Further studies involving larger and more diverse patient populations are required. Furthermore, randomized controlled trials are recommended which include studies of both herbal medicine alone and in combination with Western medicine.

The strengths of this study are as follows. First, to our knowledge, this is the first study to evaluate the effectiveness and safety of Cheongpebaedok-tang through telemedicine treatment in Korea. Additionally, this study provided detailed information on patient management by examining the time of self-isolation, confirmation, symptom onset, facility isolation, and release of patients taking herbal medicines, which have not been provided in previously published Korean medicine telemedicine studies. A final strength of this study is that the observation of negative results was likely more accurate because the isolation release criteria in Korea at that time required two negative PCR test results. Notably, unlike previous studies that reported starting treatment from the initial COVID-19 diagnosis, this study showed significant results, even though the treatment was started an average of 19.4 days after diagnosis. This suggests that Cheongpebaedok -tang can be prescribed without being limited for use only as an initial treatment; thus, the scope of application of Cheongpebaedok-tang through telemedicine treatment in clinical settings may be broader than previously thought. The treatment of patients with mild COVID-19 should be safe, have few side effects, and be easy to administer. In particular, telemedicine treatment for patients with mild diseases can protect doctors from exposure, is more convenient and cost-effective, and provides continuous treatment by efficiently allocating limited healthcare resources.33–35) Jang et al. also investigated telemedicine treatment using Korean medicine for COVID-19 and determined that this approach was a satisfactory and convenient treatment for patients, and the second most frequently prescribed herbal medicine was Cheongpebaedok-tang.13) In conclusion, Korean telemedicine management based on the administration of Cheongpebaedok-tang is a potential treatment for patients with mild COVID-19.

In Korean medicine, the visual evaluation of the tongue and sputum is an important component for diagnosing respiratory diseases. The color, shape, and coating of the tongue reflect the condition of the internal organs and the degree and progression of disease.36) Therefore, tongue evaluation represents an important aspect of telemedicine; thus, a method for computerizing and automating tongue diagnosis/evalution is being studied.37,38) The viscosity, quantity, and color of sputum are other important qualities to use for obtaining a diagnosis39); Chinese and Korean COVID-19 medical guidelines also suggest using the appearance of sputum and the condition of the tongue as distinguishing points for symptoms.5,8) Although an evaluation of the tongue and sputum could not be performed owing to the limitations of telephone counseling in the telemedicine center, the accuracy of treatment is expected to increase if automated tongue diagnosis/evaluation and multimedia treatment through sputum pictures are introduced in the future.

Conclusion

This retrospective case series suggested the potential efficacy and safety of Korean telemedicine using Cheongpebaedok-tang for individuals with asymptomatic or mild COVID-19. It indicated relief in major COVID-19 symptoms with manageable, mild side effects, and no exacerbations leading to hospitalization during the treatment period.

Data availability

Data supporting the findings of this study are available from the corresponding author upon reasonable request.

Article information Continued