Abstract
Background
Olfactory dysfunction (OD) is a common symptom of Corona Virus Disease 2019 (COVID-19). It is defined as the reduced or distorted ability to smell during sniffing (orthonasal olfaction) and represents one of the early symptoms in the clinical course of COVID-19 infection. A large online questionnaire-based survey has shown that some post-COVID-19 patients had no improvement 1 month after discharge from the hospital.
Objective
To explore the efficacy of acupuncture for OD in COVID-19 infected patients and to determine whether acupuncture could have benefits over sham acupuncture for OD in post-COVID-19 patients.
Methods
This is a single-blind, randomized controlled, cross-over trial. We plan to recruit 40 post-COVID-19 patients with smell loss or smell distortions lasting for more than 1 month. Qualified patients will be randomly allocated to the intervention group (real acupuncture) or the control group (sham acupuncture) at a 1:1 ratio. Each patient will receive 8 sessions of treatment over 4 weeks (Cycle 1) and a 2-week follow-up. After the follow-up, the control group will be subjected to real acupuncture for another 4 weeks (Cycle 2), and the real acupuncture group will undergo the 4-week sham acupuncture. The primary outcomes will be the score changes on the questionnaire of olfactory functioning and olfaction-related quality of life at week 6, 8, 12, and 14 from the baseline. The secondary outcomes will be the changes in the olfactory test score at week 6 and 12 from the baseline measured by using the Traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC).
Discussion
The results of this trial will help to determine the effectiveness of acupuncture for OD in post-COVID-19 patients. This may provide a new treatment option for patients.
Keywords: Olfactory dysfunction, Smell loss, Smell distortions, COVID-19, Acupuncture, Chinese medicine, UPSIT
1. Background
In May 2020, olfactory dysfunction (OD) was recognized as a symptom of corona virus disease 2019 (COVID-19).1 OD is defined as the reduced or distorted ability to smell during sniffing (orthonasal olfaction) or eating (retronasal olfaction) and may represent an early symptom in the clinical course of infection. The loss of smell has been reported to occur before (11.8%), after (65.4%), or at the same time (22.8%) as other general or otolaryngological symptoms.2, 3, 4, 5
According to a large online questionnaire-based survey, OD in COVID-19 is usually severe and sudden in onset, but transient in most patients; however, 10.6% of patients show no improvement after 1 month.6 Common neurodegenerative disorders such as Alzheimer's and Parkinson's diseases have a well-known association with the loss of smell. If the loss of smell is an isolated symptom, a sensorineural cause is most likely, and it usually occurs after viral infections caused by pathogens other than COVID-19; the loss of smell does not change from day to day and may be profound.7
In Hong Kong, China, many individuals have self-reported the sudden changes in smell loss or smell distortions associated with COVID-19 infection.8 However, due to the lack of long-term follow-up, there is insufficient evidence to conclude to what extent this is influenced by coexisting olfactory loss or whether it is a genuine independent consequence of COVID-19. At present, there is evidence suggesting that most patients suffer impaired gustation as a consequence of a diminished sense of olfaction; thus, the focus of assessment and treatment is directed largely toward the nose.6 Several prognostic factors regarding the individual prognosis of untreated olfactory disorders are available. The magnitude of the effect of this impairment on health, safety, and quality of life is a public health concern.
It is believed that acupuncture may provide a resolution for OD. Some of the published papers have reported that acupuncture can induce significant improvement in smell function in patients with OD.9 , 10 We, therefore, propose performing a patient-blind, randomized controlled, cross-over study to evaluate whether acupuncture may be beneficial to post-COVID-19 patients who have a moderate or severe grade of OD.
Through this study, we expect to assess the effects of acupuncture on OD patients in whom olfaction has not recovered after COVID-19 infection and to compare the results with the sham acupuncture group.
2. Methods
2.1. Ethical approval
The protocol has been approved by the Hong Kong Baptist University Human Research Ethics (Clinical) Committee (Hong Kong, China) on the Use of Human Subjects for Teaching and Research (REC/20–21/0508), Hospital Authority Kowloon Central/Kowloon East Research Ethics Committee (KC/KE-21-0054/FR-3), and registered in clinicaltrials.gov (NCT04959747). Written consent will be taken from all the eligible and willing participants before they participate in the study. The protocol version number is 1.0 dated April 15, 2021. This study is not actively recruiting.
2.2. Study design
This is a single-blind, randomized sham-controlled, cross-over clinical trial. Post-COVID-19 patients presenting with smell loss or smell distortions will be recruited from the Department of Medicine to the Department of Ear, Nose, and Throat (ENT) in Tseung Kwan O Hospital (TKOH) for further assessment. The screening will be conducted at the Department of ENT on Visit 0 using the Traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). Patients with a moderate or severe grade of OD (based on UPSIT-TC scores, the cutoff scores are set at 29.5 for males and 30.5 for females) will be recruited. Forty qualified patients will be invited to participate in the study. They will be referred to the Chinese Medicine Clinic cum Training and Research Centre (CMCTR) for further action, such as providing written informed consent, assessment, and acupuncture treatment. The objective of this study will be to investigate the OD of COVID-19 patients using subjective validated patient-reported outcome questionnaires and objective psychophysical testing. The study flowchart is shown in Fig. 1 . Trials (Standard Protocol Items: Recommendations for Interventional Trials, SPIRIT) checklist is provided as Supplemental File 1, and the schedule of enrolment, intervention, and assessments is shown in Table 1 .
Fig. 1.
Study flow chart.
Note: OD: olfactory dysfunction.
Table 1.
Showing time points for enrolment, allocation, interventions, and assessment.
| Item | Enrolment | Baseline | Treatment |
Follow-up | ||||
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | Cycle 2 | |||||||
| Time point | 0 | 1 | 2–8 | 9 | 10 | 11–16 | 17 | 18 |
| Enrolment | ||||||||
| Eligibility screening | X | NA | NA | NA | NA | NA | NA | NA |
| Informed consent | NA | X | NA | NA | NA | NA | NA | NA |
| Randomization | NA | X | NA | NA | NA | NA | NA | NA |
| Allocation | NA | X | NA | NA | NA | NA | NA | NA |
| Intervention | ||||||||
| Real Acupuncture | NA | NA |  |
|
NA | |||
| Sham Acupuncture | NA | NA | |
|
NA | |||
| Assessments | ||||||||
| UPSIT-TC | X | NA | X | NA | X | NA | ||
| ASOF | NA | X | X | X | X | X | ||
| sQOD-NS | NA | X | X | X | X | X | ||
Notes: UPSIT-TC: Traditional Chinese version of the University of Pennsylvania Smell Identification Test; ASOF: Assessment of self-reported olfactory functioning and olfaction related quality of life; sQOD-NS: Short version of the Questionnaire of Olfactory Disorders-Negative Statements. X: Measurement taken by the OD patients.
2.3. Setting and recruitment
The study will be conducted at 3 departments of TKOH, Hong Kong, China, comprising Department of Medicine, Department of ENT, and Department of Chinese Medicine: Haven of Hope—the Chinese University of Hong Kong CMCTR (China).
2.4. Inclusion criteria
Patients previously diagnosed with COVID-19 and discharged from local hospitals will be included if they meet the following criteria: (1) the presence of post-COVID-19 OD of moderate or severe grade (based on UPSIT-TC scores; the cutoff scores are set at 29.5 for male and 30.5 for female individuals)11; (2) no treatment for post-COVID-19 OD; (3) no history of trauma, injury, or surgery to head or nose, or any bleeding from the nose; (4) age 18–80 years; and (5) ability to read and write Chinese.
2.5. Exclusion criteria
Patients will be excluded if they meet 1 or more of the following criteria: (1) presence of olfactory or gustatory dysfunctions before the COVID-19 epidemic; (2) history of chronic rhinosinusitis or nasal polyposis; (3) history of nasal surgery (including rhino/septoplasty with or without functional endoscopic sinus surgery); (4) pregnancy or breastfeeding; (5) medical history of cancer, conditions of the nervous system such as Parkinson's disease or Alzheimer's disease, and/or any other serious diseases; (6) unstable medical conditions; (7) acupuncture treatment received within 1 month; (8) alcoholism or drug abuse in the past year; (9) presence of needle phobia; and (10) known history of developing acupuncture-related severe adverse reactions.
2.6. Screening
Post-COVID-19 patients presenting with smell loss or smell distortions will be referred from the Department of Medicine to the Department of ENT in TKOH for further assessment. The screening will be conducted at the Department of ENT of TKOH on Visit 0 using UPSIT-TC (a 40-item olfactory test, which is widely used internationally). Forty qualified patients will then be invited to participate in the study and will be referred to the CMCTR for further action.
2.7. Baseline visit
After screening, all eligible patients will be scheduled for a baseline visit in the CMCTR. During the visit, each patient will be further assessed by the Chinese Medicine Practitioner (CMP) Co-investigator (Co–I) using the 12-item validated questionnaire for the assessment of self-reported olfactory functioning and olfaction-related quality of life (ASOF) and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). The answers to the ASOF and sQOD-NS reported by the patient will be filled in by the study team.
The CMP Co–I will inform the patient about the details of the study and obtain his/her written informed consent. Upon signing the informed consent, the patient will be randomly assigned either to the acupuncture group (AC) or to the sham acupuncture group (SAC). Intervention (Cycle 1 treatment period) will start after a 2-week run-in period.
2.8. Randomization and blinding
Forty qualified patients will be randomly assigned to 2 groups, the acupuncture group (AC) and the sham acupuncture group (SAC) at a 1:1 ratio, for 4-week treatment and 2-week follow-up. After the follow-up, the sham group will undergo real acupuncture treatment for another 4 weeks, while the real acupuncture group will be subjected to the 4-week sham acupuncture treatment.
Simple, complete, nonsequential randomization numbers will be generated by Random Allocation Software 2.0.0 (Isfahan University of Medical Sciences, Isfahan, Iran) and kept by Principal Investigator (PI). To reduce the risk of breaking the blinding, that is, to reduce bias as much as possible, the trial will be patient-blinded, and data collection staff and data analysts will be also blinded during the study period. The acupuncturist will not be blinded to the treatment to be delivered because acupuncture manipulation makes this impossible.
The randomization list will only be available to the PI and the acupuncturist, and will not be available to any person involved in the conduction and evaluation of the trial until the trial database is locked.
2.9. Sample size and calculation
Since this is a pilot study and there has been no acupuncture study for COVID-19 patients with OD, the sample size calculation is based on the primary outcome measurement. We assume that there will be a 30% improvement in the acupuncture group compared with the control group. Considering the power of 80% and the alpha value of 2.5% (two-tailed), each group will need at least 32 subjects for the significance to be detected. Allowing for a 20% drop-out, we plan to recruit 40 subjects in each group. As this will be a cross-over study, while the total sample size will be 80, we only need to recruit 40 patients.
2.10. Intervention
Each patient will be scheduled for a total of 8 sessions of acupuncture treatment, 30 min per session, twice per week, over 4 weeks. The selection of acupuncture points will be based on traditional Chinese medicine (TCM) theory12 , 13 and evidence-based clinical research14 in the CMCTR. According to the TCM theory, Yintang (EX-HN 3) is a local point and is indicated in the treatment of frontal headaches, eye disorders, rhinitis, sinusitis, and insomnia. In Chinese, Yingxiang (EX-HN 3) means “welcome fragrance”. Yingxiang (LI 20) is indicated in nasal obstruction and loss of smell sensation. Needling Yingxiang (LI 20), in traditional terms, helps the “lung” to perform its dispersing function, so that the nose can smell the fragrant scent. Shangxing (GV 23) is used as a local point for the nose and frontal sinus.15, 16, 17, 18, 19 The acupuncture points selected for the treatment are listed in Table 2 and Fig. 2 . A total of 8 needles for 8 acupuncture points will be used for each acupuncture treatment session.
Table 2.
Acupuncture points.
| Acupuncture point | Anatomical location | Function according to TCM |
|---|---|---|
| Yingxiang (LI 20) | On the face, in the nasolabial sulcus, at the same level as the midpoint of the lateral border of the ala of the nose | Dispels exterior wind |
| Bitong (EX-HN 18) | On the region of the face, at the junction of the cartilage of the ala nasi and the nasal concha, near the upper end of the nasolabial groove | Benefits the nose |
| Shangxing (GV 23) | On the head, 1 cun superior to the anterior hairline, on the anterior median line | Opens the nose |
| Yintang (EX-HN 3) | Midway between the medial ends of the 2 eyebrows | Eliminates wind, stops convulsions, and calms the mind |
| Hegu (LI 4) | On the dorsum of the hand, radial to the midpoint of the second metacarpal bone | Dispels exterior wind, releases the exterior, stimulates the dispersing function of the lungs, stops pain, removes obstructions from the channel, tonifies qi and consolidates the exterior, and harmonizes ascending and descending functions |
Notes: TCM: traditional Chinese medicine.
Fig. 2.
Locations of the acupuncture points.
2.11. Education of acupuncturists
The acupuncturists assigned to perform acupuncture intervention on the participants will be CMPs at the CMCTR, who have received acupuncture training, have at least 3 years of clinical experience in performing acupuncture, and have experience in treating OD.
2.12. Acupuncture (AC) group
Disposable acupuncture needles provided by CMCTR (0.25 mm in diameter and 25–30 mm in length) will be inserted at a depth of 10–25 mm obliquely into the scalp acupuncture points including Shangxing (GV 23) and Yintang (EX-HN 3), and straightly into the face/body acupuncture points including Yingxiang (LI 20), Bitong (EX-HN 18) and Hegu (LI 4). Electro-acupuncture will be applied to the face points including Yingxiang (LI 20), Bitong (EX-HN 18), Yintang (EX-HN 3) at fast and dispersed waves through an electric needle stimulator provided by CMCTR (Hwato, Electronic Acupuncture Treatment instrument, Suzhou Medical Appliance Factory, Suzhou, China) for 30 min. The intensity will be adjusted to a level at which the patient feels comfortable. The alternating stimulation is believed to produce maximal biochemical responses in the brain.20
2.13. Sham acupuncture (SAC) group
For subjects assigned to the control group, School of Chinese Medicine, Hong Kong Baptist University (Hong Kong, China) will provide Streitberger's noninvasive acupuncture needles. They will be applied to serve as sham control at the same acupoints with the same stimulation modality, except that the needles will only be adhered to the skin instead of inserting them to the skin. The validity and credibility have been well demonstrated.
The placebo needle (in SAC group) looks like a real acupuncture needle and appears to penetrate the skin like a real acupuncture needle. It will be applied at the real acupuncture points with the same stimulation modality, except that the needles will only be adhered to the skin by a small plastic ring instead of being inserted into the skin, and the stimulation will be a “pseudo stimulation”, which will be given by connecting the needle to an incorrect output socket of the electrical acupuncture stimulation instrument.21 Therefore, the patients cannot visually distinguish between sham and active acupuncture procedures.
The participants will not be able to distinguish between the sham acupuncture procedure and the active acupuncture procedure because as the placebo needle is pushed against the skin, it causes a pricking sensation. Moreover, when increased pressure is applied, the shaft of the placebo needle disappears into the handle, which gives the impression that the placebo needle is entering the skin.22 In Streitberger's research, it was reported that none of the 60 volunteers suspected that the needle might not have penetrated the skin.23
3. Outcome measures
3.1. Assessments and time points
Assessments will be performed at baseline and at every protocol-defined interval (Table 3 ) until the study completion or the study drop-out.
Table 3.
Schedule of study visits.
| Assessments and procedures | Screening | Baseline | Cycle 1 treatment period |
Cycle 2 treatment period |
Last follow-up | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Visit | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 |
| Check and confirm participant eligibility | X | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| UPSIT-TC | X | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | X | NA |
| ASOF | NA | X | NA | NA | NA | NA | NA | NA | NA | X | X | NA | NA | NA | NA | NA | NA | X | X |
| sQOD-NS | NA | X | NA | NA | NA | NA | NA | NA | NA | X | X | NA | NA | NA | NA | NA | NA | X | X |
| Acupuncture session | NA | NA | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | NA |
| 2-week follow up visit after cycle 1 treatment | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | X | NA | NA | NA | NA | NA | NA | NA | NA |
| 2-week follow up visit after cycle 2 treatment (last follow up) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | X |
Notes: There will be 19 study visits in total. UPSIT-TC: to be conducted by Co–I Dr. Cho in the Department of ENT, TKOH, during Visit 0 and Visit 17. For Visit 17, the UPSIT-TC in the Department of ENT will be scheduled on the same day as the acupuncture session, ASOF, and sQOD-NS in the CMCTR. Acupuncture session: to be conducted by CMPs in the CMCTR during Visit 2 to Visit 17. UPSIT-TC: traditional Chinese version of the University of Pennsylvania smell identification test. NA: not available.
3.2. Primary outcomes
The primary outcomes will be ASOF and sQOD-NS. The ASOF is a 12-item validated questionnaire, which can be subdivided into 3 domains: the one-item subjective olfactory capability (SOC) scale, the 5-item self-reported capability of perceiving specific odors (SRP) scale, and the 6-item olfactory-related quality of life (ORQ) scale. We calculated the cutoff scores for the 3 scales. Patients will be considered to have abnormal olfactory capabilities if the SOC score is equal to or less than 3. Patients will be considered to have problems with smelling odors if the SRP score is equal to or less than 2.9. Patients will be considered to have smell-related problems in the quality of life if their ORQ score is equal to or less than 3.7.24
The sQOD-NS is a 7-item patient-reported outcome questionnaire. Patients rate the item proposition from 0 (agree) to 3 (disagree), with a total score ranging from 0 (significant impact of OD on QOD) to 21 (no impact on QOD). The sQOD-NS is composed of 7 questions including social behavior, eating, annoyance, and anxiety, which are assessed using a 4-point Likert scale (0–3). A higher score means better olfactory-specific QOD.25
3.3. Secondary outcomes
The secondary outcome will be UPSIT-TC. The University of Pennsylvania Smell Identification Test (UPSIT) is widely used internationally and is the worldwide standard for olfactory testing. It is a 40-item “scratch and sniff” multiple-choice test to assess how well participants can identify different odors. Patients will be required to identify each of the 40 odors from the 4 alternatives listed for each odor. The number of correct responses will provide a test score such that patients can be categorized into one of 4 categories: mild, moderate, severe, or total loss. The test is scored by the number of odors identified correctly to generate a maximum score of 40. UPSIT-TC is a modified version of UPSIT in traditional Chinese medicine developed for administration in Taiwan, China, with the deletion of a few odors that are unfamiliar and the addition of a few odors. The UPSIT-TC and its validated cutoff scores used in Taiwan, China, are currently being used in the clinical practice in Hong Kong, China. The UPSIT-TC cutoff scores for OD in our study are based on the validated study in Taiwan, China (the establishment of olfactory diagnosis for UPSIT-TC, 2016),26 which was based on the assessment of 1440 enrolled subjects. An olfactory diagnosis of UPSIT-TC has been established in relation to gender and age. In addition, the cutoff scores between normosmia and mild hyposmia were established at 29.5 for males aged 20–59 years and at 30.5 for females aged 20–59 years.26 , 27 The different cutoff scores between male and female adults were further analyzed in another study published in 2019 (sex differences in human olfaction: a meta-analysis), and the results of their meta-analysis indicated that women generally outperformed men in olfactory abilities.28
4. Data collection, management, and analysis
An independent data monitoring committee will be established to periodically monitor the quality, accuracy, and completeness of all data collected. Training will also be provided to all study personnel, and cross-validation through interrater reliability will be performed with the universities’ expert involvement.
A data monitoring committee will be established and led by the PIs. Co–I will be responsible for periodically monitoring the quality, accuracy, and completeness of all data collected. Training will also be provided to all study personnel, and cross-validation through interrater reliability will be performed with the expert involvement.
A senior research assistant (RA) will be responsible for handling the data to ensure the authenticity and accuracy of the study data. All electronic data will be protected by a password. Files will be anonymous and will be assigned a unique subject code. The completed questionnaires (hard copies) will be kept in a locked cabinet inside study sites or research offices. Study data will be kept anonymous with unidentifiable code on study documents, and we will follow the Hong Kong (China) Hospital's policy on handling, storage, and disposal of all research data.
5. Statistical analysis
All efficacy and safety analyses will be conducted according to the intention-to-treat (ITT) principle. Missing values will be imputed by the last-observation-carried forward method. The statistical analysis will be performed using SPSS 25.0 (IBM Corp., Armonk, NY). The statistical significance is defined as a two-sided P-value <.05. Baseline differences between the groups will be assessed with Student's t test (for normally distributed continuous variables) or the nonparametric Mann–Whitney U test (for non-normally distributed variables). For categorical variables, the chi-square test or Fisher's exact test will be used. Changes in scores at each evaluation time point from baseline will be analyzed using Analysis of Covariance (ANCOVA), followed by the Bonferroni t test to detect differences between 2 groups at each time point. The same analysis will be repeated within the 2 different treatment cycles of each subject to examine the within-subject difference. The incidence of adverse events will be examined using the chi-square test.
6. Plans to promote participant retention and complete follow-up
This study requires the eligible participants to attend assessment sessions and follow-up visits and to fill in questionnaires and undergo related assessments. To maximize the participants' compliance, a thorough consent process will be provided for all participants, with details of the study schedule, the participants’ responsibilities, and our support. Participants will be free to withdraw at their discretion without penalty. The research team will attempt to call the participants who dropped out.
7. Dissemination plans
RA will be responsible for handling the data to ensure the authenticity and accuracy of the study data. Only PIs, Co–I, RA, and regulatory authorities (e.g., monitors, auditors, and ethic committees) have the authority to check the documents.
8. Confidentiality
The personal data will be used for research purposes only. All the data will be destroyed after 3 years since the completion of the research study.
9. Potential risks and patient safety
Acupuncture is generally a safe method of treatment, but it may have side effects such as bruising, minor bleeding, and numbness or tingling at or near the needle site, which may last for a few days. Unusual risks of acupuncture include fainting, spontaneous miscarriage, nerve damage, and organ puncture. Infection is another possible risk; however, since we only use sterilized, disposable needles while maintaining a clean and safe environment, this is unlikely. Moreover, if patients feel unwell during the acupuncture treatment, we will stop the treatment immediately, and treat them appropriately as soon as possible. The study is also covered by a professional liability insurance policy.
10. Discussion
The sense of smell is of great importance in our daily life. It continuously informs us about our surroundings, warns us about potential air hazards, and along with the sense of taste, it determines the taste and smell of food. There is a strong connection between smells and memory, and olfaction has a great influence on a person's emotional state. Thus, the magnitude of the effect of olfaction impairment on health, safety, and quality of life is of public health concern. In Hong Kong, China, many individuals have self-reported the sudden changes in smell loss or smell distortions, which are associated with COVID-19 infection. However, due to the lack of long-term follow-up, there is insufficient evidence to conclude to what extent this is influenced by coexisting olfactory loss or whether it is a genuine independent consequence of COVID-19. It has been reported that 40%–50% of COVID-19 patients globally present changes in the sense of smell and taste.29 Acupuncture has been practiced for at least 2000 years in China, and the effectiveness of acupuncture treatment for improving olfactory function has been reported in recent decades.9 , 30 Therefore, this study will assess the potential effects of acupuncture on OD due to COVID-19.
It has been suggested that olfactory function may recover spontaneously. Among 18 studies with 3699 patients, 74.1%, 85.8%, 90.0%, and 95.7% of patients recovered their sense of smell at 30, 60, 90, and 180 days, respectively. The median recovery time was 14.9 days. Moreover, patients with higher initial severity of smell dysfunction were less likely to recover the olfactory function.31 Therefore, the possibility of spontaneous recovery of the olfaction should be taken into account.
However, our study has some limitations. First, the sample size of the trial should be larger. Considering that the pandemic is now slowing down in Hong Kong, China, it may be difficult to recruit more patients in a short time. Future studies need to increase the sample size and determine whether the observed increase in olfactory sensitivity is temporary or lasts for a longer period. Acupuncture plays an active role in traditional Chinese medicine. The results of this trial are expected to provide convincing evidence that acupuncture is effective for OD in post-COVID-19 patients and whether traditional acupuncture theories play an important role in it.
Funding
This research was jointly-supported by Hong Kong Baptist University (SCM-2020-001), Haven of Hope -The Chinese University of Hong Kong Chinese Medicine Clinic cum Training and Research Centre (Sai Kung District), and Tseung Kwan O Hospital of Hospital Authority, Hong Kong, China, on expenses and equipment.
CRediT authorship contribution statement
Linda Lidan Zhong: Writing – original draft, writing – review & editing, and funding acquisition. Yiping Wong: Writing – original draft, and writing – review & editing. Choryin Leung: Writing – original draft, and writing – review & editing. Chifung Choy: Investigation, and writing – review & editing. Hungwai Cho: Investigation, and writing – review & editing. Alan Yatlun Wong: Investigation, and writing – review & editing. Kaming Yau: Writing – review & editing. Rowena Howwan Wong: Writing – review & editing. Bacon Fungleung Ng: Funding acquisition, and writing – review & editing. Zhaoxiang Bian: Project administration, supervision, and writing – review & editing.
Declaration of competing interest
The authors declare that they have no conflicts of interest. Prof. Zhaoxiang Bian is an editorial board member of Journal of Traditional Chinese Medical Sciences. He was excluded from the review process of this paper.
Acknowledgment
We would like to thank Sonia Goh, research assistant, for the revision of the protocol and case report form. Written informed consent was obtained from the patient(s) for the publication of this manuscript and accompanying images.
Footnotes
Peer review under responsibility of Beijing University of Chinese Medicine.
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jtcms.2022.11.003.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
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