Acupressure in the treatment of patients with mild infection of COVID-19 omicron variant: A prospectively observational study

Abstract

During the coronavirus disease 2019 epidemic, acupressure has been widely used as a complementary treatment for coronavirus disease 2019 in China, but its safety and effectiveness have not been determined until now. This was a prospectively observational study containing 400 cases of mild infection of Omicron who were admitted to Chongming Flower Expo Makeshift Hospital from April 1, 2022 to May 1, 2022. Patients were assigned to receive basic treatment or a combination with acupressure treatment (5 minutes per acupoint, at least twice daily), from admission to discharge. The conversion time of viral RNA assay, the recovery time of symptoms and the clinical cure rate at day 7 were compared in 2 groups. All cases were included in the final analysis. The time to conversion of viral RNA assay (6 vs 7 days, P < .001) and time to symptom recovery (2 vs 4 days, P < .001) were markedly shortened in the acupressure treatment group compared to controls. The time to recovery from individual symptoms of coughing, a sore throat, a fever, fatigue, poor appetite, and insomnia were shorter in the treatment group compared to the control (all P < .05), but there was no statistical difference in reducing the recovery time from headache, muscle ache, anxiety, loss of taste between 2 groups (all P > .05). In addition, acupressure therapy also revealed a higher clinical cure rate at day 7 than basic treatment alone (91% vs 65%, P < .001) and reported no serious adverse events. This study provided evidence for acupressure therapy in treatment of Omicron infection concerning the viral load disappearance and the clinical symptoms improvements. Findings were expected to help guide efforts to position acupressure therapy as a therapeutic option for patients with Omicron variant.

1. Introduction

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly escalated into a worldwide public health emergence.^[1,2] As of June 28 2023, at least 767 million infections and 6.94 million deaths induced by this epidemic have been reported to WHO.

With the constant mutation of the SARS-CoV-2, many new variations have appeared across the globe.^[3] Among them, the Omicron variant has been regarded as the predominantly circulating strain in most countries since November 2021.^[4] The replication and pathogenicity of this new strain has been reported to be attenuated and to result in asymptomatic or milder symptoms in patients.^[5–7] Nevertheless, the Omicron caused more infections in a large population base will put a large-scale of strain on the healthcare system and national financial system.^[8–10]

Traditional Chinese Medicine (TCM) has accumulated successful experience in controlling pestilence for thousands of years. During COVID-19 epidemic, TCM treatment was included in the Chinese treatment protocol, which achieved excellent efficacy in intervening patients at various stages with SARS-CoV-2 infection.^[11,12] Acupressure therapy, as an economical and side-effect free natural remedies, is one of the most important therapeutic methods in TCM. It involves pressing and scraping at defined points with blunt objects such as cotton swabs, fingers or chopsticks. It is reported that COVID-19 patients have benefited from this noninvasive treatment, including alleviation of clinical symptoms and amelioration of by-effect of routine therapies.^[13,14] Relevant literature has pointed out acupressure can relieve upper respiratory discomfort and enhance patient’s quality of life.^[15,16] Similarly, acupressure therapy has been confirmed to actively suppress viral infection-triggered inflammatory response and subsequently preserve lung function in another study.^[17] Evidently, these discourses shed novel light on the management and treatment of Omicron infection, and it can be sufficiently envisaged that acupressure therapy may become 1 promising intervention for the effective control of omicron infection.

However, most of the articles on utilizing acupressure intervention to treat this disease have remained at the stage of theoretical exploration.^[18–20] And related researches of curative effect observation are also rare. The efficacy of acupressure in patients with Omicron variants cannot be scientifically evaluated until now. Therefore, our research set out to investigate the safety and effectiveness of acupressure intervention in the treatment of Omicron infected patients, thereby providing a basis for clinical application and popularization of acupressure treatment for COVID-19.

2. Materials and methods

2.1. Study design

A prospectively observational study was adopted to comprehensively observe the efficacy and safety of acupressure therapy in patients with mild infection of COVID-19 Omicron variant in the Chongming Flower Expo Makeshift Hospital in Shanghai. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Second Affiliated Hospital of Anhui University of Chinese Medicine (No.2022-zjks-26). All patients agreed to participate in this study and obtained written informed consent from participants.

2.2. Patients

Eligible patients were cases of a laboratory-confirmed Omicron infection. All patients presented with mild symptoms such as a sore throat, coughing, or other discomfort. Moreover, patients were admitted with no computed tomography evidence of pneumonia.^[21]

Excluded criteria were prespecified as follows: Aged > 80 years; Severe or critical pneumonia; Patients with severe vital organ disease, such as organ failure, malignant tumor, and intracerebral hemorrhage; Patients administered herbal medicines, or other traditional Chinese medicines; Administered acupressure treatment in the control group; Any other conditions that the researchers deemed the patients to be unsuitable for taking part in the study.

2.3. Procedures

From April 1, 2022 to May 1, 2022, a total of 400 patients who were admitted to Chongming Flower Expo Makeshift Hospital in Shanghai were enrolled into this study. Then they were divided into 2 groups based on whether they received acupressure treatment (preset exposure factor in this study). The control group accepted only basic treatment in ward A, while the treatment group accepted additional acupressure therapy in ward B. Patients in control group and treatment group were arranged in 2 separate areas, which avoided both sides knowing the other’s treatment methods. On the day of admission, demographic information, disease history, vital signs, COVID-19 symptoms, and nucleic acid testing result were collected for each patient as the baseline data. During hospitalization, the results of real-time polymerase chain reaction test for virus, the COVID-19 symptoms and treatment-associated side effects were monitored and recorded by clinicians every day. The treatment courses were retrospectively summarized at the end of follow-up.

2.4. Interventions

Based on the Diagnosis and Treatment Protocol for Coronavirus Pneumonia (Trial version 9), the control group was given basic treatment at the discretion of the attending clinicians, generally consist of; Bed rest, supportive treatment to ensure sufficient heat, water and electrolyte balance to maintain internal environment stability, and close monitoring of vital signs and oxygen saturation; Timely effective oxygen therapy measures, including nasal catheter, mask oxygen, and transnasal high-flow oxygen therapy; Antiviral therapy (nirmatrelvir–ritonavir has been suggested to be used, 300 mg nirmatrelvir and 100 mg ritonavir, every 12 hours for 5 consecutive days); Antibiotic therapy if bacterial infection was confirmed. Detailed information about basic treatment is shown in Table 1.

Table 1.

Detailed information about basic treatment.

Basic treatment	Treatment group (n = 200)	Control group (n = 200)	P value
Supportive therapy (n, %)
Bed rest, Supportive treatment to ensure sufficient heat, Water and electrolyte, Balance to maintain internal environment stability, Close monitoring of vital signs and oxygen saturation	200 (100)	200 (100)	1
Oxygen therapy (n, %)
Nasal high-flow oxygen therapy	13 (6.5)	16 (8)	.335
Antiviral therapy (n, %)
Receiving nirmatrelvir–ritonavir	0 (0)	0 (0)	1
Antibiotic therapy (n, %)
Amoxicillin capsules	17 (8.5)	23 (11.5)	.317
Cefprozil tablets	10 (5)	15 (7.5)	.302
Moxifloxacin hydrochloride tablets	6 (3)	4 (2)	.522
Other symptomatic therapies (n, %)	7 (3.5)	10 (5)	.457

In addition to basic treatment, the treatment group was given additional acupressure therapy until discharge. Based on Guidance for acupuncture and moxibustion interventions on COVID-19 (Second edition),^[22] the following acupoints were used, including Feishu (BL13), Shaoshang (LU11), Shangyang (LI1), Dazhui (DU14), Waiguan (SJ5), Quchi (LI11), Fenglong (ST40), Yinlingquan (SP9), Zusanli (ST 36). The patients use their thumb pulp to press the above acupoints (perpendicular to the skin surface direction for 8 seconds consecutive pressing and 2 seconds rest), 5 minutes for each acupoint, at least twice a day. The force of pressing varies from person to person, depending on patient’s tolerance. Before the first treatment, patients would receive acupressure exercises under the guidance of specialized therapists who had 10 years of clinical experience in acupressure therapy, and was provided with predetermined paper and video versions of the exercises including. Only after patients performed the exercises skillfully, then they could conduct this acupressure treatment independently. The daily treatment completions of all patients were recorded. If the subject received any other treatment regimen, the changes should be recorded on the Clinical Report Form each time.

2.5. Outcome measures

The primary endpoints consisted of the conversion time of nucleic acid as well as the recovery time from all symptoms. Symptom recovery refers to the complete disappearance of the clinical symptoms. The secondary outcome measures were recovery time from individual symptoms and the clinical cure rate at day 7. The clinical cure rate in this study was defined as meet the following criteria: Resolution of all clinical symptoms; No computed tomography evidence of pneumonia; 2 consecutive negative oropharyngeal swab real-time polymerase chain reaction (at least 24 hours apart).

2.6. Safety monitoring

The safety indicators were treatment-related adverse events. The incidence, time, seriousness, duration and relatedness of adverse events were recorded. The correlation between adverse events and treatment was assessed by clinical investigators.

2.7. Statistical analysis

SPSS software 26.0 (vers 26.0, IBM Institute, Chicago, IL) was utilized for statistical analyses in this study. The counting (percentage) method was utilized to summarize categorical variables, and a chi-square test was utilized for comparison of values. Continuous variables were represented as means and standard deviations, and an independent t test or Wilcoxon rank-sum test was utilized for comparison of values. The time to events was expressed with the median duration and 95% confidence interval (CI), and analyzed with Kaplan–Meier analysis. There was also a demonstration of the hazards ratio (HR) of the events. As virus negative conversion and symptoms recovery were beneficial events, the higher HR value would increase the likelihood of benefit of the acupressure treatment. Statistical significance was defined as P < .05.

3. Results

3.1. Basic characteristics

No major protocol violation occurred in each group. Hence, the entire 400 cases with Omicron infection were included in the final analyses. The demographic and clinical characteristics of the patients at baseline are shown in Table 2. Neither group differed in age, gender, underlying diseases and clinical symptoms (P > .05).

Table 2.

Comparison of baseline demographic and clinical characteristics.

Variables	Treatment group (n = 200)	Control group (n = 200)	P value
Age, yr (−x ± s)	38.29 ± 12.83	39.09 ± 12.57	.376
<18 (n, %)	8 (4)	4 (2)	.241
18–35 (n, %)	85 (42.5)	84 (42)	.919
36–59 (n, %)	101 (50.5)	101 (50.5)	1
60–80 (n, %)	6 (3)	11 (5.5)	.215
Gender
Male (n, %)	134 (67)	134 (67)	1
Female (n, %)	66 (33)	66 (33)	1
Combined underlying diseases (n, %)	26 (13)	29 (14.5)	.6631
Obesity (n, %)	2 (1)	3 (1.5)	.652
Blood pressure (n, %)	4 (2)	8 (4)	.241
Diastolic (n, %)	4 (2)	4 (3)	1
Hyperlipidemia (n, %)	1 (0.5)	2 (1)	.562
Coronary heart disease (n, %)	4 (2)	1 (0.5)	.177
Cerebrovascular disease (n, %)	4 (2)	3 (1.5)	.703
Other diseases (n, %)	8 (4)	9 (4.5)	.804
Symptoms
Cough (n, %)	133 (66.5)	118 (59)	.121
Sore throat	59 (29.5)	54 (27)	.230
Fever (n, %)	43 (15)	37 (18.5)	.353
Fatigue (n, %)	11 (5.5)	8 (4)	.481
Muscle ache (n, %)	6 (3)	5 (2.5)	.759
Headache (n, %)	2 (1)	8 (4)	.481
Poor appetite (n, %)	12 (6)	19 (9.5)	.191
Insomnia (n, %)	11 (5.5)	17 (8.5)	.239
Anxiety (n, %)	3 (1.5)	8 (4)	.2
Loss of taste (n, %)	4 (2)	6 (3)	.52

3.2. Primary end points

In accordance with the results of nucleic acid tests, the acupressure treatment showed a significantly shorter median conversion time for virus nucleic acids in comparison to the control (6 vs 7 days, HR: 2.267, 95% CI: 1.847–2.781, P < .001) (Figs. 1A and 2A). Similarly, a remarkedly reduction in the median recovery time from all symptoms was observed in acupressure group than in the control (2 vs 4 days, HR: 2.985, 95% CI: 2.404–3.707, P < .001) (Figs. 1B and 2B).

Figure 1.

The comparison of the virus negative time and recovery time from all symptoms between two groups. (A) The virus negative time, (B) recovery time from all symptoms. Shown in the figure are the median value and 95% confidence intervals (95% CI).

Figure 2.

Dynamic changes in the negative rate of virus nucleic acid and recovery rate of all symptoms between two groups in Kaplan–Meier survival curve. (A) The negative rate of virus, (B) the recovery rate of symptom.

3.3. Second end points

In this study, the time to recovery from individual symptoms including coughing (2 vs 4 days, HR: 3.21, 95% CI: 2.43–4.25, P < .001), a sore throat (2 vs 4 days, HR: 2.86, 95% CI: 1.90–4.31, P < .001), a fever (2 vs 4 days, HR: 2.48, 95% CI: 1.56–3.93, P < .001), fatigue (2 vs 3.5 days, HR: 3.66, 95% CI: 1.05–6.79, P = .042), poor appetite (2 vs 4 days, HR: 3.07, 95% CI: 1.39–6.78, P = .006), and insomnia (1 vs 3 days, HR: 5.74, 95% CI: 2.18–15.15, P < .001) were remarkedly shorter in the acupressure group compared to the control (Fig. 3A and B). However, in term of reducing symptomatic period of patients with headache (2.0 vs 4 days, HR: 3.51, 95% CI: 1.188–6.97, P = .557), muscle ache (2 vs 4 days, HR: 2.022, 95% CI: .593–6.891, P = .261), anxiety (2 vs 3 days, HR: 3.741, 95% CI:.752–18.616, P = .107), or loss of taste (2 vs 3.5 days, HR: 1.873, 95% CI: .496–7.073, P = .354), no statistical difference was found between these 2 groups (Fig. 3B). In addition, treatment with acupressure therapy was associated with a higher clinical cure rate at day 7 than with basic treatment alone (91% vs 65%, P < .001) (Fig. 4).

Figure 3.

The comparison of recovery time from a single symptom between two groups. (A) The recovery time from cough, sore throat, fever, fatigue, and poor appetite, (B) the recovery time from headache, muscle ache, insomnia, anxiety, and loss of taste. Shown in the figure are the median value and 95% confidence intervals.

Figure 4.

The comparison of the number of cases of clinical cure at day 7 between two groups.

3.4. Safety

No adverse reactions or complications were reported in 2 groups, and no medical staffs were infected.

4. Discussion

In the face of the continuous evolution of SARS-CoV-2 variants, epidemic prevention and treatment are becoming increasingly challenging.^[9] Currently, the Omicron variant is the predominantly circulating strain in most continents, which appeared in November 2021 in southern Africa and subsequently dominating the pandemic.^[23] In particularly, cumulative evidence has demonstrated that Omicron variants are highly transmissible and significantly resistant to serum neutralization, even in convalescent population and people accepted booster vaccines.^[11,24] In this regard, the emergence of Omicron undoubtedly constitutes a particularly pernicious threat to safeguarding global public health during the pandemic.^[4]

Chinese patent medicines such as Shufeng Jiedu capsule were proposed to be effective in inhibiting the Omicron virus replication and alleviating patients symptoms.^[21,25] However, given that huge and rising numbers of patients with Omicron and overload of the medical system, existing drugs are far from satisfying current medical needs.^[26] Therefore, convenient, secure, and cost-effective medical care services for millions of people are needed.

As an important branch of TCM, acupressure therapy is performed widely in China. It is a technique of pressing or/and rubbing acupoints with a finger or noninvasive tool.^[27] Manipulations performed on specific acupoints can stimulate the meridians Qi, resulting in the regulating of the channels and balancing of energy, thus restoring the body to normal health, which has been proven to be effective in many medical and psychological disorders.^[28] In the past few decades, various acupressure therapies have been applied to facilitate the recovery process of patients with respiratory diseases. S H Maa et al^[29] reported acupressure as an adjunct to a pulmonary rehabilitation program for patients with chronic obstructive pulmonary disease. A systematic review evaluated the manual therapy involving massage, acupressure, and tuina training on patients suffered from chronic obstructive pulmonary disease, the results of which were characterized to be safe, feasible and effective.^[30] In addition, a randomized controlled trial conducted by Nurhan Doğan on the effect of acupressure on lung cancer patients showed that the physical and functional performance of lung cancer patients had improved.^[16] Relevant researches in China have also confirmed that this therapy could ameliorate both lung symptoms and mental health of patients with pulmonary disease by precluding an injury from foreign virus through regulating innate immunity.^[15,16,31] Obviously, these studies have shown promising evidence for COVID-19 management. Notably, in virtue of the advantages of few but precise acupoint prescriptions, simple operation steps and convenient material selection of acupressure therapy, people can easily find the appropriate tools for self-operation even in a makeshift hospital with extremely limited resources. And this intervention is compatible with a telerehabilitation approach that minimizes contact with COVID-19 patients to avoid hospital-acquired infections. There is no doubt that it presents higher operability and cost-effectiveness under the prevalence of the Omicron variant (in case of self-isolation, shortage of medical resources, and lack of personal protective equipment).^[32] Both the country and the individual will benefit more from acupressure if the efficacy of it in treating patients with Omicron infection is confirmed.

According to the theory of TCM, the clinical efficacy can be strengthened by acupoint prescription and compatibility. Recently, a study with 2108 cases of COVID-19 Omicron variant infection in Changchun has reported that people with such symptoms like cough, fatigue, sore throat, and a fever accounted for 76.66%, 47.96%, 46.25%, and 19.97% respectively.^[33] In light of these circumstances, selecting acupoints to ameliorate these symptoms would be the key to manage COVID-19 Omicron infection. Feishu (BL13) is the response point of the lungs in the back and Shaoshang (LU11) belongs to the lung meridian, they can directly reach the sick position to protect lungs through stimulation. Some researchers have indicated that these acupoints are effective in relieving symptoms of coughing and sore throat.^[34] Zusanli (ST 36) is an important tonifying point, 1 meta-analysis has showed that massage on Zusanli can relieve fatigue and improve immune function.^[35] Meanwhile, SARS-CoV-2 infections has been reported to cause damage to the digestive system.^[36,37] Interestingly, the compatibility of Zusanli (ST 36), Fenglong (ST40), and Yinlingquan (SP9) can develop a good regulating effect on patients with gastrointestinal symptoms. In addition, Dazhui (DU14), Quchi (LI11), and Waiguan (SJ5) have been widely used to dispel heat and toxic for fever patients in TCM. In summary, combination of the above acupoints can achieve the purpose of improving symptoms, shortening the course of disease and speeding up recovery. Consequently, we selected these points to treat people infected with Omicron in acupressure treatment group.

In our study, treatment with acupressure therapy significantly shortened the conversion time of virus nucleic acid, and improved the negative rate of virus (37.0% at day 5, 74.5% at day 6 and 91% at day 7), suggesting that acupressure treatment may speed up viral shedding. Furthermore, acupressure therapy also remarkedly reduced the symptomatic period by 2 days. And symptomatic effectiveness was shown to be significant for patients with sore throat, coughing, fever, fatigue, insomnia, and poor appetite, but not with headache, muscle ache, anxiety, or loss of taste, which provides a basis for selective application of acupoint pressing to a certain extent. In addition, the higher clinical cure rate at day 7 might also be attached to anti-SARS-CoV-2 activity, the inhibition of inflammatory response as well. No adverse reactions were observed, supporting the safety of NIA for treating people with Omicron infection.

Despite promising results, however, our study has several limitations. First, due to the urgency of the outbreak and limited resources, this study still exists some insufficiency such as few observation indicators and too single enrolling cases. Second, the observation time was short, and data were only recorded during the patients stay in the hospital. And patients who achieved clinical cure before day 7 were regarded as day 7 for statistical analysis, which may lead to an underestimation of the efficacy of acupressure therapy. Therefore, it is necessary to further study the long-term clinical efficacy of acupressure for mild COVID-19 of Omicron variant. Third, except for sparse reports, the actual underlying mechanisms of acupressure therapy are still not fully known, and there is a clear need for more laboratory and clinical research to confirm the mechanism of acupressure. Finally, though an observational study can be an important complement, it does not replace RCTs. A large-scale randomized, double-blinded, placebo-controlled clinical trial remains indispensable.

It is worth mentioning that although this study was initially designed to prove the effectiveness and safety of acupressure in the treatment of COVID-19 infection, it may continue to be a promising and cost-effective intervention during the post-COVID era. Future research can further explore the impact of acupressure on the many symptoms experienced by patients during and after COVID-19 infections.

5. Conclusion

In conclusion, our fundings supports that acupressure therapy showed beneficial efficacy in the management of patients with mild COVID-19 of Omicron Variant. It could significantly shorten the time to conversion of viral RNA assay and symptom recovery, which played a critical role in accelerating the recovery of patient infected with omicron. In view of efficacy and safety, we therefore recommend that health care providers consider position acupressure therapy as a therapeutic option for COVID-19 patients and increase the popularization and application of this therapy in clinical practice.

Acknowledgements

We thank all participants for their efforts in this study.

Author contributions

Conceptualization: Qiqi Yang, Tianxin Jiang.

Data curation: Shouliang Ma, Wen Liu, Fei Li.

Formal analysis: Shouliang Ma, Fei Li.

Investigation: Baoguo Wang.

Methodology: Meng Li.

Supervision: Meng Li, Fei Li.

Writing – original draft: Qiqi Yang, Tianxin Jiang, Baoguo Wang, Jie Wang.

Writing – review & editing: Shouliang Ma, Shaofei Chen, Meng Li, Fei Li.