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J Acupunct Meridian Stud 2022; 15(4): 247-254

Published online August 31, 2022 https://doi.org/10.51507/j.jams.2022.15.4.247

Copyright © Medical Association of Pharmacopuncture Institute.

The Adjunctive Effects of Acupuncture for Hospitalized COVID-19 Patients: a Single-Blinded Randomized Clinical Study

Dwi Rachma Helianthi1 , Atikah C. Barasila1,2 , Salim Harris3 , Robert Sinto4 , Yordan Khaedir2 , Irman1,*

1Department of Medical Acupuncture, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo National Central Public Hospital, Jakarta, Indonesia
2Department of Histology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
3Department of Neurology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo National Central Public Hospital, Jakarta, Indonesia
4Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo National Central Public Hospital, Jakarta, Indonesia

Correspondence to:Irman
Department of Medical Acupuncture, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
E-mail francis.solanus@gmail.com

Received: June 3, 2021; Revised: July 7, 2022; Accepted: May 5, 2022

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a coronavirus (SARS-CoV-2) that can induce cytokine storm. To this point, no specific drug has been effective for curing COVID-19.
Objectives: The aim of this study was to determine the effects of a combination of acupuncture intervention and pharmacologic treatment in hospitalized COVID-19 patients with mild-moderate symptoms.
Methods: A single-blinded randomized controlled clinical trial of hospitalized COVID-19 patients confirmed by RT-PCR examination with mild-moderate symptoms was conducted from August to September 2020. Participants were assigned to the treatment group (receiving pharmacologic treatment and manual acupuncture intervention) or the control group (receiving only pharmacologic treatment). Laboratory outcomes, including complete blood count, C-reactive protein (CRP) and ferritin levels, and erythrocyte sedimentation rate (ESR), were measured before and after the intervention. For clinical outcomes, we evaluated the duration of the cough symptom.
Results: We found that participants in the treatment group had a shorter duration of the cough symptom compared to the control group, and the difference was statistically significant. In the treatment group, we found an increase in the percentage of lymphocyte count and ESR, while in the control group, both parameters were decreased; however, the differences were not statistically significant. There was a decrease in the mean of CRP and ferritin levels in both groups, and the differences were not statistically significant.
Conclusion: Our study has shown promising results for the effects of combined treatment of acupuncture and pharmacologic treatment on the duration of the cough symptom in hospitalized COVID-19 patients with mild-moderate symptoms. Further large-scale studies with rigorous design are needed to examine these preliminary results.

Keywords: Acupuncture, COVID-19, Inflammation

INTRODUCTION

Coronavirus disease 2019 (COVID-19) is a problem faced by more than 200 countries globally, including Indonesia [1]. The World Health Organization (WHO) has declared the COVID-19 outbreak a pandemic. SARS-CoV-2 infection into the host cells cause an immune response from the host, which cause an inflammatory reaction in the host’s body. Inflammation that occurs increases the level of pro-inflammatory cytokines and chemokines, such as Interleukin-1 (IL-1), IL-6, and Tumor Necrosis Factor-α (TNF-α) [2]. To this point, there has been no specific drug to prevent or treat COVID-19. Treatment is aimed at symptomatic patients and consists of supportive therapy [3,4]. Currently, there have been no published studies on acupuncture clinical trials examining inflammatory markers in COVID-19 patients. However, according to clinical trial research conducted in several cases with pathophysiology similar to COVID-19 conditions, acupuncture can play a role in regulating the immune system and providing anti-inflammatory effects, so acupuncture is expected to provide benefits in preventing cytokine storm [5-7]. In the competent hands and with regard to the contraindications, acupuncture is a safe practice. The most commonly encountered side effects are pain and hematoma at the needle insertion site, which are mild and temporary [8,9].

In this study, researchers sought to determine the effects of a combination of acupuncture intervention and pharmacologic treatment in hospitalized COVID-19 patients with mild-moderate symptoms with three times per week frequency of acupuncture for a total of six acupuncture sessions.

MATERIALS AND METHODS

1. Study design

We conducted a single-blinded randomized controlled clinical trial of hospitalized adult COVID-19 patients with mild-moderate symptoms. All study participants signed an informed consent letter. This study was approved by the Health Research Ethics Committee Faculty of Medicine Universitas Indonesia (KET-845/UN2.F1/ETIK/PPM.00.02/2020).

2. Procedures and participants

We recruited participants at the Duren Sawit Regional Special Hospital of Jakarta in August–September 2020. The inclusion criteria for this study were hospitalized patients at least 18 years of age with mild-moderate symptoms of COVID-19 (confirmed by RT-PCR swab examination). COVID-19 patients with mild symptoms are those with uncomplicated viral respiratory tract infections with non-specific symptoms, such as fever, weakness, cough (with or without sputum production), anorexia, malaise, muscle pain, sore throat, breathlessness, nasal congestion, and headache. Although rare, patients may complain of diarrhea, nausea, or vomiting. Elderly and immunocompromised patients may present atypical symptoms. The patients do not develop viral pneumonia or hypoxia [10]. COVID-19 patients with moderate symptoms are adult patients with clinical signs of pneumonia (i.e., fever, cough, dyspnea, tachypnea) but no signs of severe pneumonia, and they do not require oxygen supplementation. Severe pneumonia is characterized by one of the following symptoms: respiratory rate > 30 bpm, severe respiratory distress, or oxygen saturation (SpO2) < 93% in room air or a PaO2/FiO2 ratio < 300 [10]. Exclusion criteria were patients with contraindications to manual acupuncture (pregnancy, hemostatic disorders, random blood glucose levels > 200 mg/dl, acute infection at puncture site) and those with myeloproliferative disorders.

Calculation of the number of samples in this study was done using the sample size formula to compare two independent means with a confidence interval of 5%, power 80%, SD value 15.74, and X1-X2 value 21.1 from previous research with the largest number of samples [11]. With the drop-out rate 20%, a sample of 11 subjects in each group was obtained.

3. Randomization & blinding

Study participants were recruited through direct interviews by researchers. The participants were randomly divided into two groups—the treatment and control groups—with simple randomization without stratification. Each participant is assigned a serial number. Then, each number was linked to a computer-generated random list. The treatment group included 11 participants who received the pharmacologic treatment for hospitalized COVID-19 patients with mild-moderate symptoms and acupuncture intervention. The control group included 11 participants who received only the pharmacologic treatment.

The single blinding in this study was assessor blinding at the time of outcome assessment. Laboratory analysts assessed laboratory outcomes, and COVID-19 ward nurses assessed the clinical outcome (cough). Laboratory analysts and nurses did not know to which group the subjects belonged.

4. Intervention

The acupuncture intervention was given for two weeks, with a frequency of three times per week for six sessions and with a duration of about 30 minutes for each session. The acupuncture intervention was performed by a qualified physician who completed a full acupuncture training course [12] and was supervised directly by the principal investigator. Study participants were asked to report the development of clinical symptoms or other complaints. All participants were instructed not to participate in any other studies during the study period. Both groups received the pharmacologic treatment for COVID-19 patients (Chloroquine 2 × 300 mg, Azithromycin 1 × 500 mg, Oseltamivir 2 × 75 mg, Vitamin C 2 × 250 mg, and Zinc 2 × 20 mg) (Fig. 1) [13].

Figure 1. Acupuncture points LI4 Hegu, LI11 Quchi, ST36 Zusanli [13].

We performed manual acupuncture on both sides of the dorsum of the hand (LI4 Hegu), on the elbows (LI11 Quchi), and on both sides of the Tibia (ST36 Zusanli).

We used 0.25 × 25 mm acupuncture needles (Dong Bang®, China). The needle is pricked and then stimulated by twirling once, and the needle is retained for 30 minutes.

In the control group, the study participants received only pharmacologic treatment for COVID-19 patients. The pharmacologic treatment provided at the hospital at the time of our research was Chloroquine 2 × 300 mg, Azithromycin 1 × 500 mg, Oseltamivir 2 × 75 mg, Vitamin C 2 × 250 mg, and Zinc 2 × 20 mg.

5. Outcomes and follow-up

Clinical findings, such as cough symptoms and laboratory results, were taken before the participants received treatment. Clinical symptoms were evaluated daily. Meanwhile, laboratory tests (complete blood count, CRP, ESR, ferritin) were checked after two weeks of treatment (hospitalization).

The diagnosis of COVID-19 was confirmed by an RT-PCR swab examination performed prior to hospital admission.

The primary outcome is the improvement of laboratory results, such as increased percentage lymphocyte count, decreased levels of CRP, ferritin, and ESR, and clinical improvement (i.e., shorter duration of cough symptom).

At each follow-up visit, participants were asked if they had any adverse effects from the acupuncture intervention. In addition, participants were provided with a telephone number to report if they had any side effects about which they were concerned due to the study. Finally, any adverse effects were documented on the case report form and reported to the principal investigator.

6. Statistical methods

Baseline characteristics were presented using the mean and standard deviation (SD), and categorical data were presented as proportions. A Chi-square test was performed on categorical data. An independent t-test and repeated ANOVA measurement test were performed on continuous variables. Previously, the normality test was carried out using the Shapiro–Wilk test to determine the data distribution. The analysis was carried out based on the “intention to treat.” The effect of acupuncture intervention on the number of lymphocytes, serum CRP levels, serum ferritin levels, and ESR was carried out using the repeated ANOVA measurement test. Cough onset and cough duration were analyzed using the independent T-test. The significance of the test results was determined based on the p-value < 0.05. Statistical analysis was performed using SPSS version 26. The effect size was calculated using GPower software version 3.1.9.6. According to Cohen, r ≥ 0.10 represents a small treatment effect, r ≥ 0.30 represents a medium treatment effect, and r ≥ 0.50 represents a large treatment effect [14].

RESULTS

We recruited 34 hospitalized COVID-19 patients with mild-moderate symptoms at Duren Sawit Hospital in Jakarta as participants. However, 12 patients declined to participate, so 22 patients were randomized as study participants. All participants completed the study.

The mean age was 43.5 years, and there were more female (68.18%) than male (31.81%) participants. In this study, several comorbidities were found, including hypertension (27.3%), diabetes (13.6%), obesity (13.6%), and asthma (4.5%). We also found that two participants (9%) were smokers. Of the 22 participants, 100% were exposed to contact with a PCR-positive COVID-19 patient (Table 1, Fig. 2).

Age and onset of cough were calculated using an independent t test; gender, co-morbidities, smoking history, and contact history of COVID-19 patients were calculated using a chi square test..

&md=tbl&idx=1' data-target="#file-modal"">Table 1

Baseline characteristics.

CharacteristicsIntervention group (n = 11)Control group (n = 11)p-value
Age (years)42 ± 14.7145 ± 11.670.602
Gender0.500
Male3/114/11
Female8/117/11
Co-morbidities760.665
Hypertension3 (27.3%)3 (27.3%)
Diabetes Mellitus03 (27.3%)
Obesity3 (27.3%)0
Asthma1 (9.1%)0
Smoker0.762
Yes11
No1010
COVID-19 contact1.00
Yes1111
No00
Onset of cough (days)7.55 ± 2.0187.64 ± 2.0140.917

Age and onset of cough were calculated using an independent t test; gender, co-morbidities, smoking history, and contact history of COVID-19 patients were calculated using a chi square test..



Figure 2. Participants flow diagram.

1. Changes in lymphocyte count percentage

The mean lymphocyte count percentage before the intervention was 26 ± 6.387% in the treatment group and 26 ± 11.474% in the control group. This mean difference was not statistically significant (p = 0.176). After the intervention, the mean lymphocyte count percentage was 28.45 ± 6.46% in the treatment group and 24.36 ± 6.58% in the control group. This difference was not statistically significant (p = 0.568), as seen in Table 2.

Data were represented as mean ± standard deviation..

&md=tbl&idx=2' data-target="#file-modal"">Table 2

The result of the percentage lymphocyte count, CRP, ferritin, ESR before and after acupuncture treatments.

OutcomeGroupBefore treatmentAfter treatmentEffect sizep-value
Lymphocyte (%)Control26 ± 11.47424.36 ± 6.580.630.568
Intervention26 ± 6.38728.45 ± 6.46
CRP (mg/dL)Control22.27 ± 23.707.45 ± 2.420.650.397
Intervention31 ± 35.5679.82 ± 4.54
Ferritin (mcg/L)Control532.02 ± 606.54328.46 ± 209.440.250.977
Intervention598.79 ± 850.79272.84 ± 227.48
ESR (mm)Control36.55 ± 32.2930.45 ± 27.550.180.920
Intervention34.27 ± 28.0235.09 ± 24.00
Cough duration (days)Control4.91 ± 1.381.190.01
Intervention3.45 ± 1.04

Data were represented as mean ± standard deviation..



After the intervention, there was an increase in the lymphocyte count percentage in the treatment group and a decrease in the lymphocyte count percentage in the control group. This can be seen in Fig. 3.

Figure 3. Comparison of lymphocyte, CRP, ferritin, ESR before and after treatment between groups.

2. Changes in C-reactive protein level

The mean CRP level before the intervention was 31 ± 35.567 mg/dl in the treatment group and 22.27 ± 23.70 mg/dl in the control group. This mean difference was not statistically significant (p = 0.634). After the intervention, the mean CRP level was 9.82 ± 4.54 mg/dl in the treatment group and 7.45 ± 2.42 mg/dl in the control group. This difference was not statistically significant (p = 0.397), as seen in Table 2.

After the intervention, there was a decrease in the CRP level in both groups, but the reduction in CRP level was greater in the treatment group, as seen in Fig. 3.

3. Changes in ferritin level

Before the intervention, the mean ferritin level was 598.79 ± 850.79 mcg/L in the treatment group and 532.02 ± 606.54 mcg/L in the control group. This mean difference was not statistically significant (p = 0.640). After the intervention, the mean ferritin levels were 272.84 ± 227.48 mcg/L in the treatment group and 328.46 ± 209.44 mcg/L in the control group. This difference was not statistically significant (p = 0.977), as seen in Table 2.

After the intervention, there were decreased ferritin levels in both groups, but the decrease in ferritin levels was greater in the treatment group than in the control group. This can be seen in Fig. 3.

4. Changes in erythrocyte sedimentation rate

The mean ESR before the intervention was 34.27 ± 28.02 mm in the treatment group and 36.55 ± 32.29 mm in the control group. This mean difference was not statistically significant (p = 0.292). After the intervention, the mean ESR was 35.09 ± 24 mm in the treatment group and 30.45 ± 27.55 mm in the control group. This difference was not statistically significant (p = 0.920), as seen in Table 2.

ESR in the treatment group increased, and the control group decreased after the intervention. This can be seen in Fig. 3.

5. Changes in the cough symptom

At recruitment, we assessed cough symptoms by determining their onset based on the time the participants were hospitalized. In addition, we wanted to analyze the duration of the cough symptom between the treatment and control groups. After two weeks, it was found that the mean duration of the cough symptom was 3.45 ± 1.04 days in the treatment group and 4.91 ± 1.38 days in the control group. This difference was statistically significant (p = 0.01).

Table 2 shows that the acupuncture intervention on cough duration showed a large effect, an increase in the number of lymphocytes and a decrease in the CRP level showed a medium effect, while the decrease in ferritin and ESR levels showed a small effect.

We found that three participants in the treatment group experienced hematomas during the study due to acupuncture needle insertion. The hematomas were mild and resolved spontaneously within 5-7 days. There was no incidence of acushock or infection at the acupuncture needle insertion site.

DISCUSSION

This study is a pilot study in Indonesia examining the effect of the combination of acupuncture intervention and pharmacologic treatment in COVID-19 cases. Until this article was written, there were only two published acupuncture clinical trial studies for COVID-19 with the randomized controlled trial design [15,16]. Both studies were published in Chinese, and only one study examined objective examination. The current study involved 22 hospitalized COVID-19 patients with mild-moderate symptoms, confirmed by an RT-PCR swab examination.

This study’s results follow the study’s objectives to determine whether adjunct acupuncture with the pharmacologic treatment for COVID-19 patients with mild-moderate symptoms has a positive effect. We found that participants in the treatment group had a shorter duration of the cough symptom, compared to the control group, and the difference was statistically significant. Moreover, the results of some laboratory outcomes generally showed potential benefits for the treatment group. Although statistical significance was not reached, the treatment group showed better improvement, demonstrated by an increased number of lymphocytes and decreased levels of CRP and ferritin. However, since our study was conducted on a small scale, these findings suggest the potential promise of this combined treatment. Therefore, it is essential to conduct further research referring to the standard deviation produced in this study. For the ESR outcome, we found that there was an increase in ESR in the treatment group. After we examined the data thoroughly, there was an increase in ESR in both the treatment group (four subjects) and the control group (two subjects). Out of these two subjects in the control group, one had hypertension, and the other was known to have no comorbidities. Meanwhile, in the treatment group, we found three obese subjects and one hypertensive subject who experienced an increase in ESR. Patients with the obesity comorbidity were only found in the treatment group. Obesity is known to be a condition with chronic inflammation [17]. Therefore, it is necessary to further research COVID-19 and obesity.

The cough symptom in COVID-19 patients is caused by damage to the epithelium and endothelium of the upper respiratory tract due to inflammation caused by infection with the SARS-CoV-2 virus [18]. Therefore, the researcher determined the length of the cough period to be from when the patient entered the hospital until the subject was cough-free. The results of this study showed that cough symptoms were shorter in the treatment group (3.45 ± 1.04 days) than in the control group (4.91 ± 1.38 days), and this difference was statistically significant (p = 0.01). Furthermore, there was a faster improvement in cough symptoms in the treatment group, indicating that the inflammation in the upper airway of the treatment group subjects subsided more quickly. In this regard, although statistical significance was not reached, greater reductions in CRP and ferritin levels in the treatment group were found.

This study’s selection of acupuncture points was based on clinical trials of acupuncture for several cases where the acupuncture mechanisms act as an anti-inflammatory and regulate the immune system [11,19-22]. This is because the pathology of COVID-19 and the patient’s condition are closely related to biomarkers associated with inflammation and immune system. For example, hyperferritinemia (ferritin > 400 mcg/L) is associated with inflammatory conditions in SARS-CoV-2 infections; therefore, ferritin can be used as a parameter to predict disease severity and the likelihood of a cytokine storm [23]. One of the causes of lymphocytopenia in COVID-19 patients is increased levels of pro-inflammatory cytokines, including TNF-α and IL-6. TNF-α has been reported to have a suppressive effect on the process of hematopoiesis and can cause cytopenia. It has been reported that IL-6 levels in COVID-19 patients are associated with impaired cytotoxic activity on T cells and NK cells. Increased levels of pro-inflammatory cytokines also lead to the induction of granulopoiesis and myelopoiesis and the suppression of lymphopoiesis in the bone marrow. Due to the increase in monocytes and granulocytes, the levels of pro-inflammatory cytokines increase, and the number of lymphocytes decreases [24]. CRP is a non-specific acute-phase protein. Its production is induced by the presence of IL-6 in the liver. CRP is a sensitive biomarker for inflammation, infection, and tissue damage. More than 55% of COVID-19 patients with mild symptoms have elevated CRP levels. The SARS-CoV-2 infection causes cellular damage, and if the therapy cannot inhibit the viral infection, an exaggerated inflammatory response causes tissue and organ damage. Therefore, elevated serum CRP levels in patients with COVID-19 may indicate excessive inflammatory stress and contribute to the onset of severe/critical symptoms or even death. The higher the serum CRP level in the body of a COVID-19 patient, the higher the risk that the patient will develop severe symptoms [25]. Among the laboratory tests used to assess acute-phase inflammatory reactions, ESR is considered the least specific. ESR is affected by various other physiological and pathophysiological conditions, thus narrowing its usefulness to certain clinical conditions. Nevertheless, ESR continues to be used in routine laboratory examinations of patients, regardless of clinical questions. Although ESR lacks analytical and diagnostic specificity, its determination can contribute to managing COVID-19 symptoms and can provide additional information about disease progression [26].

Acupuncture has long been known to have anti-inflammatory effects. Stimulation of acupoint LI4 can activate the vagus-cholinergic anti-inflammatory pathway, which can increase acetylcholine’s release; acetylcholine binds to α7nAChR receptors on macrophages and inhibits the release of pro-inflammatory cytokines [7]. Stimulation of acupoint ST36 activates the vagus-medulla adrenal-dopamine’s anti-inflammatory pathway, causing the release of dopamine, which can bind to type I dopamine receptors and inhibit pro-inflammatory cytokines IL-6, INF-γ, TNFα and can increase survival in sepsis patients [7]. Stimulation of acupoints LI11 and ST36 can inhibit the activation of TLR-4 and NF-κB, reducing the production of pro-inflammatory cytokines TNFα, IL-1β, and IL-6 [27]. Stimulation of acupoints LI4 and ST36 has been shown to increase ACTH and cortisol levels in the blood [7]. Direct suppression of IL-6 production causes a decrease in CRP and ferritin levels [21,28].

The limitations of this study include the following. COVID-19 is a new disease for which there is no explication regarding diagnostic criteria, so changes in diagnostic markers may occur rapidly. In addition, there is no standard medical management for COVID-19, so there are variations in medical management between centers. Furthermore, the number of study participants is too small; in this study, we carried out simple randomization. Meanwhile, to classify subjects based on comorbidities, stratified randomization is necessary to avoid bias from comorbidities.

CONCLUSIONS

Our single-blinded randomized clinical trial has shown promising results for the effects of the combined acupuncture and pharmacologic treatments on the duration of the cough symptom in hospitalized COVID-19 patients with mild-moderate symptoms. Although statistical significance was not reached, potential benefits of the combined treatment was suggested by some laboratory outcomes (percentage lymphocyte count, CRP level, and ferritin level). As the number of subjects is small, further research must be conducted with a larger sample size involving several centers. Further research could also assess the effects of the combined treatment on other COVID-19-related symptoms, such as anosmia, gastrointestinal symptoms, and hypercoagulation.

FUNDING

The authors declare that there was no specific grant given for this research from any public, commercial, or not-for-profit funding agency.

AUTHORS' CONTRIBUTIONS

All authors contributed to the study concept and design. Dwi Rachma Helianthi and Salim Harris conducted the main statistical analysis. Salim Harris, Robert Sinto, and Yordan Khaedir contributed to the literature review and interpretation of the data. Dwi Rachma Helianthi and Irman contributed to drafting the report. Dwi Rachma Helianthi, Atikah C Barasila, Salim Harris, and Robert Sinto provided administrative, technical, and material support and supervised the study. All authors revised the text for intellectual content and have read and approved the final version of the manuscript.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Fig 1.

Figure 1.Acupuncture points LI4 Hegu, LI11 Quchi, ST36 Zusanli [13].
Journal of Acupuncture and Meridian Studies 2022; 15: 247-254https://doi.org/10.51507/j.jams.2022.15.4.247

Fig 2.

Figure 2.Participants flow diagram.
Journal of Acupuncture and Meridian Studies 2022; 15: 247-254https://doi.org/10.51507/j.jams.2022.15.4.247

Fig 3.

Figure 3.Comparison of lymphocyte, CRP, ferritin, ESR before and after treatment between groups.
Journal of Acupuncture and Meridian Studies 2022; 15: 247-254https://doi.org/10.51507/j.jams.2022.15.4.247

Table 1 . Baseline characteristics.

CharacteristicsIntervention group (n = 11)Control group (n = 11)p-value
Age (years)42 ± 14.7145 ± 11.670.602
Gender0.500
Male3/114/11
Female8/117/11
Co-morbidities760.665
Hypertension3 (27.3%)3 (27.3%)
Diabetes Mellitus03 (27.3%)
Obesity3 (27.3%)0
Asthma1 (9.1%)0
Smoker0.762
Yes11
No1010
COVID-19 contact1.00
Yes1111
No00
Onset of cough (days)7.55 ± 2.0187.64 ± 2.0140.917

Age and onset of cough were calculated using an independent t test; gender, co-morbidities, smoking history, and contact history of COVID-19 patients were calculated using a chi square test..


Table 2 . The result of the percentage lymphocyte count, CRP, ferritin, ESR before and after acupuncture treatments.

OutcomeGroupBefore treatmentAfter treatmentEffect sizep-value
Lymphocyte (%)Control26 ± 11.47424.36 ± 6.580.630.568
Intervention26 ± 6.38728.45 ± 6.46
CRP (mg/dL)Control22.27 ± 23.707.45 ± 2.420.650.397
Intervention31 ± 35.5679.82 ± 4.54
Ferritin (mcg/L)Control532.02 ± 606.54328.46 ± 209.440.250.977
Intervention598.79 ± 850.79272.84 ± 227.48
ESR (mm)Control36.55 ± 32.2930.45 ± 27.550.180.920
Intervention34.27 ± 28.0235.09 ± 24.00
Cough duration (days)Control4.91 ± 1.381.190.01
Intervention3.45 ± 1.04

Data were represented as mean ± standard deviation..


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