A hallmark of severe coronavirus disease 2019 (COVID-19) is acute respiratory distress syndrome (ARDS). The estimated time from the first symptoms to ARDS and to intensive care unit (ICU) admission are 8.0-9.0 and 9.5-10.5 days, respectively. The reported prevalence of ARDS is approximately 41.8% in hospitalized patients with a mortality of approximately 22%, which varies geographically [1,2].

Currently, no treatment options with strong evidence of clinical benefit exist. Thus, national and international guidelines recommend using experimental drugs as part of investigational trials [2]. There is a high demand and urgent global need to develop specific therapies against severe acute respiratory syndrome associated with coronavirus 2 (SARS-CoV-2) [1].

In the face of the new pandemic, the role of complementary and alternative medicine (CAM) in recognizing and treating COVID-19 and researchers’ experiences with CAM that can benefit other countries are important aspects that warrant discussion [3]. The World Health Organization (WHO)-China Joint Mission fully confirms the success of “China’s model” against COVID-19 in a report that was published in February 2020. The report also specifically demonstrates the highly effective role of non-pharmaceutic measures. In fact, one particular power in “China’s model” is cupping [4].

As a non-pharmacological treatment of Traditional Chinese Medicine (TCM) and Persian Medicine (PM), cupping has been clinically used to improve respiratory symptoms such as breathlessness and cough in COVID-19. There is evidence of cupping therapy remarkably improving survival and the hospital discharge rate and increasing the curative rate in pneumonia, acute lung injury, and ARDS [5-8]. According to PM resources such as “Exireh Azam” and “Al-Havi”, warm cupping of the posterior thorax can play an important role in treatment of acute respiratory diseases [9-11].

Cupping is administered by creating negative pressure inside cups. To perform warm cupping, an alcohol-soaked cotton ball is ignited, held inside the cup with pincers for a short time, and then quickly withdrawn. This depletes the gas from the cup; thus, the skin under the cup is suctioned [12,13].

This article presents a report of the effects of warm cupping combined with routine treatment on eight cases of critically ill COVID-19-positive patients with ARDS admitted to the ICU, where staffing and resources are extremely limited as a result of the current COVID-19 pandemic.

In TCM, Urinary Bladder-13 (BL13) is the Back-Shu point of the lung, and the indications for stimulation of this point include pulmonary symptoms such as cough, expectoration, wheezing, and shortness of breath [14]. In PM cupping, the paraspinal and lung areas at the posterior thorax correspond to respiratory diseases. According to PM principles, to eliminate abnormal humors from the lungs, sliding cupping from the top of the back down toward the lumbar region should be performed [11,13].

We combined Chinese and Persian techniques of cupping in respiratory and infectious diseases. The primary method included retained warm cupping on BL13 acupoint, (on the back, 1.5 cun lateral to the lower border of the spinous process of the 3rd thoracic vertebra) for one minute. This was supplemented with sliding (moving) cupping the paraspinal (1.5 cun lateral to the spinous process of the thoracic vertebrae) and lung regions for five minutes. The procedure was performed three times a day for seven days with a medium glass (5 cm mouth diameter and 8 cm height) and a suction amount of between 10 and 15 mm.

Information on oxygen saturation (SpO₂) and symptom scores were obtained. We collected longitudinal severity scores on three symptoms (cough, shortness of breath, and unusual chest pain or chest tightness) and the type of oxygen therapy based on a National Institutes of Health (NIH)-endorsed protocol to research patient experience of COVID-19 [15]. Symptom scores were self-reported by participants every day after cupping on an ordinal scale: 1 = not affected, 2 = minimally affected, 3 = affected, and 4 = severely affected. The type of oxygen therapy was determined as follows: 1 = nasal cannula, 2 = simple face mask, 3 = mask with reservoir, and 4 = continuous positive airway pressure and a non-invasive ventilation (CPAP/NIV) mask. We also determined peripheral capillary SpO₂ just before and five minutes after cupping. In addition, SpO₂ was recorded four hours after the last cupping session each day to determine the durability effect of cupping. No interruption of the intervention occurred; thus, all patients received 21 sessions of cupping.

Due to the need to perform the cupping procedure and complete questionnaires that required the cooperation and vigilance of the patients, we did not include intubated patients in this study. After signing a written informed consent for research participation and for de-identified data to be recorded in a published case series, consecutive patients were registered in this study. Eight adults with reverse transcriptase polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection were admitted to the ICU at Shohadaye Pakdasht Hospital in Tehran province between December 1, 2020, and December 7, 2020. No changes were made in the conventional treatment of these patients. All participants were either treated with interferon beta-1b, dexamethasone, or remdesivir as part of the initial treatment for ICU-admitted patients with COVID-19 according to the Iranian National Guidelines for COVID-19 (Table 1) [16]. The demographic and clinical characteristics of the patients and their laboratory and radiographic findings at ICU admission are listed in Table 2.

SC = subcutaneous; IV = intravenous; BID = twice a day; PO = orally..

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

Treatment for COVID-19 in the intensive care unit according to the Iranian National Guidelines.

Drug	Dose	Duration (day)
Interferon beta-1b	250 μg SC once every other day	7
Remdesivir	100 mg IV once daily	5
Dexamethasone	8 mg IV once daily	10
Vitamin C	1 gr IV BID	During hospitalization
Vitamin D	1,000 mg PO once daily	During hospitalization
Enoxaparin	1 mg/kg SC once daily	During hospitalization
Atorvastatin	40 mg PO once daily	During hospitalization

SC = subcutaneous; IV = intravenous; BID = twice a day; PO = orally..

ICU = intensive care unit; IQR = interquartile range; SpO₂ = peripheral capillary oxygen saturation..

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

Clinical characteristics, laboratory data, and imaging results at ICU admission (n = 8).

Characteristic	Measurement
Age, median (IQR), years	50.63 (39-64)
Male:Female, no. (%)	4:4 (50%:50%)
Body weight, median (IQR), kg	81.25 (65-98)
Number of patients with coexisting disorders, no. (%)
Asthma	0 (0%)
Cancer	0 (0%)
Chronic kidney disease	0 (0%)
Chronic obstructive pulmonary disease	0 (0%)
Diabetes mellitus	2 (25%)
Hypertension	4 (50%)
Duration of symptoms before admission, median (IQR), days	6.63 (2-10)
Number of patients with symptoms, no. (%)
Fever	3 (37.5%)
Cough	8 (100%)
Shortness of breath	8 (100%)
Non cardiac chest pain	8 (100%)
SpO2, median (IQR), %	82.75 (78-88)
Laboratory data
White blood cell count, median (IQR), per mm3	6,330 (3,400-11,300)
Lymphocyte count, median (IQR), per mm3	1,137 (430-2,260)
Hemoglobin, median (IQR), g/dl	13.0 (11.4-15.2)
Platelet count, median (IQR), per mm3	19.2 (15.1-21.8)
Lactate dehydrogenase level, median (IQR), U/l	614 (389-970)
Aspartate aminotransferase level, median (IQR), U/l	38 (31-44)
Alanine aminotransferase level, median (IQR), U/l	46 (40-56)
Serum creatinine level, median (IQR), mg/dl	1.12 (0.74-1.6)
Prothrombin time, median (IQR), international normalized ratio	1.05 (1-1.3)
Activated partial thromboplastin time, median (IQR), s	36 (35-40)
D-dimer level, median (IQR), μg/dl	131 (0.1-436)
Troponin I positive, no. (%)	0 (0%)
Computed tomography findings
Patients with consolidation, no. (%)	4 (50%)
Patients with ground-glass opacities, no. (%)	5 (62.50%)
Patients with pulmonary infiltration, no. (%)	8 (100%)

ICU = intensive care unit; IQR = interquartile range; SpO₂ = peripheral capillary oxygen saturation..

All eight patients had at least 14 days of hospital follow-up. Upon initiation of the intervention, all participants reported improvement in symptom scores (cough, breathlessness, and chest tightness) within 24-48 hours (Fig. 1). The improvement in symptom scores matched the increase in SpO₂ as measured by pulse oximetry four hours after the last daily cupping session (Fig. 2). As demonstrated in Fig. 3, cupping promptly increased SpO₂ by as much as 3.16%. Interestingly, the greatest improvement in SpO₂ occurred during the first session of cupping, and changes after cupping decreased as the oxygen level increased during subsequent days (Fig. 3). All patients were discharged from the ICU and the hospital (no mortality), and none required invasive mechanical ventilation (Fig. 4). This study was performed in circumstances in which most patients admitted to the ICU required invasive mechanical ventilation and ultimately expired.

Figure 1. Patient symptom scores. Pt = patient; 1 = not affected, 2 = minimally affected, 3 = affected and 4 = severely affected regarding the type of oxygen therapy: 1 = nasal cannula, 2 = simple face mask, 3 = mask with reservoir and 4 = continuous positive airway pressure and non-invasive ventilation (CPAP/NIV) mask.

Figure 2. Oxygen saturation (%) four hours after the last cupping session on each day. SpO₂ = peripheral capillary oxygen saturation; Pt = patient.

Figure 3. Changes in oxygen saturation (%) by cupping. SpO₂ = peripheral capillary oxygen saturation; Pt = patient.

Figure 4. Respiratory support and days of hospitalization of individual patients. Pt = Patient; ICU = intensive care unit; CPAP = continuous positive airway pressure.

This is the first report on warm cupping of the posterior thorax in combination with routine drugs against COVID-19. Patients with severe COVID-19 often suffer from breathlessness, a dry cough, and chest tightness, which can progress to ARDS and septic shock due to a virus-induced cytokine storm–an overly aggressive immune response [17]. Therefore, any drug or manipulation that promotes the ability of the body to cope with the condition of this cytokine storm and modulate the immune system can be an effective intervention.

Cupping therapy has been applied with different degrees of proof (I to V) in numerous conditions such as cough, asthma [18], the common cold, and pneumonia [19]. Thus, cupping might be beneficial because it can regulate serum substance P, decrease serum IgE and IL-2 levels, increase serum C3 levels, and rapidly decrease inflammation [11,12,19]. Cupping tends to play a part in three mechanisms influencing the immune system. First, by creating artificial local inflammation, cupping irritates the immune system; second, it activates the complement system and enhances 50% hemolytic complement (CH50); and third, the levels of immune products, including interferon and tumor necrosis factor are enhanced by cupping. The effect of cupping on the thymus increases lymph flow in the lymphatic system [12,19]. Moreover, it can significantly reduce the number of lymphocytes in the local blood supply and increase the number of neutrophils, which may be an anti-viral mechanism of cupping [20].

The greatest improvement in SpO₂ was observed during the first session of cupping. According to TCM, this may be justified by the fact that hospitalization and inactivity lead to Blood Stasis, Vital Qi deficiency and Qi stagnation; Qi is commonly explained as life energy, and one of its functions is very close to the function of the immune system [3,4]. In the cupped region, blood vessels are expanded by the activity of certain vasodilators, such as adenosine, noradrenaline, nitric oxide, and histamine. The sudden stimulation in the first session causes a dramatic increase in the blood flow and Qi of the skin and muscles in the affected area, which in turn, leads to improved ventilation and a consequently greater increase in SpO₂ [12,19]. Subsequent sessions do not act as a sudden stimulation after stasis and stagnation and therefore create the gentler increase in SpO₂, resulting in a maintenance effect.

All patients showed an improvement in cough, shortening of breath, unusual chest pain, and SpO₂ and felt better after cupping. They described that they could inhale more effortlessly and said that their “lungs have been opened”. The negative pressure suction applied by cupping facilitates instant removal of toxins generated by purulent fluid, exudation, and germs that are stored in the tissues, making the patient feel better [19].

At the time when COVID-19 patients felt better in terms of breathing, they became less oxygen dependent, which reduced the demand for mechanical ventilation and the duration of hospital stay. However, a retrospective cohort study reported that respiratory symptoms developed in 79% of patients with ARDS. Thus, they were forced to receive mechanical ventilation, and 52% of them expired [1].

Although a small number of patients were studied in this case series, the results including improvement in cough, breathlessness, chest tightness, and SpO₂ suggest that a combination of warm cupping of the posterior thorax and standard conventional treatment may provide a good prognosis for critically ill patients with COVID-19 with ARDS. A clinical trial of this combination treatment against COVID-19 will be initiated in Iran in the near future.

This is a small case series of eight COVID-19 patients with ARDS who received 21 sessions of warm cupping in addition to conventional treatments. We cannot establish the true temporal effect of these interventions due to the small sample size and lack of a control group. Some confounders including lung injury severity and the natural course of disease should also be accounted for. Few cupping sessions and intervention days were performed, which is generally considered safe and acceptable for patients and healthcare personnel. We also cannot determine the possible effect of implementing less or more sessions of cupping. We also did not evaluate lung changes on chest CT or changes in inflammatory markers, such as C-reactive protein (CRP), lactate dehydrogenase (LDH), or procalcitonin.

To all participating patients, nurses and doctors.

AHK and MK conceived the study, participated in its design, and edited the paper. AA was responsible for the patients’ conventional treatments. AZ (Zarei), SAAM, and SFJ helped to select and contact the patients and perform cupping. AZ (Zargaran) conceived the study and edited the paper. ON and SAA was responsible for patients’ conventional treatments and facilitated the practice of this work in COVID-19 ICU. RA participated in selecting and contacting the patients, performing cupping and data collection, and writing of the original paper. All authors read and approved the final version of the manuscript accepted for publication.

This case series was approved by the Institutional Review Board at the Tehran University of Medical Sciences on 18 November 2020 (#9711309001-50315).

The authors declare no conflict of interest.