Inhalational Ethanol Therapy (Spray and Nebulized ETHO) in COVID-19 Treatment

Study Design and Oversight This study is a randomized triple-blind clinical trial with a control group and a parallel design that was conducted at the Isabn-e-Maryam hospital in Medical university of Isfhan, Iran in September 2021. participants randomly assigned in a 1:1 ratio. The study was originally intended for participants admitted to the hospital, but due to amending the country's policy of setting up respiratory clinics in hospitals and prescribing remdesivre and dexamethasone to participants with moderate COVID-19, the study was conducted in this center. Physicians of hospitalized participants were informed about the participant's referral to the respiratory center and this study.

Participants The study population consisted of positive SARS-CoV-2-PCR test. Participants had moderate COVID-19 pneumonia that was referred to the Respiratory Clinic of the Hospital. Inclusion criteria were: agreeing to implement the plan in the form of informed consent, age over 12 years, not pregnant, no history of asthma, alcoholism or epilepsy, no contraindications to ethanol. Exclusion criteria were: intolerance to inhaled ethanol, hypersensitivity or allergies to ethanol, use of drugs that interact with ethanol, and partial or incomplete treatment. Ethanol patch skin test was used to detect possible allergy to alcohol. In this experiment, a drop of ethanol was placed on a gas pad and attached to the participant's arm. After about seven minutes, symptoms such as redness, swelling or itching of the skin will be checked. These symptoms indicated the possibility of allergy or intolerance to alcohol.

Intervention Both control and intervention groups were enrolled with standard treatments based on the national clinical guidelines of Iran. The national standard treatment was intramuscular dexamethasone, 8mg/day (5 days) and 200 mg of remdesivir intravenously on day 1, followed by 100 mg of remdesivir once daily for 4 subsequent days, infused over 30 to 60 minutes. In addition to standard treatment, after obtaining consent, distilled water spray (placebo) was added in the control group and 35% ethanol spray was added in the intervention group. Two sets of 100 ml spray were provided. All of them were instructed to spray three times every 6 hours from a distance of 20-30 cm from their face, while wearing a mask and closing their eyes, and take a deep breath as they feel nebulized liquid droplets in their nose, mouth, throat, larynx and lungs. Investigators emphasized participants that this protocol must be repeated every six hours to 7 days, depending on the persistence of symptoms. How to use it was first taught by investigators and after ensuring the participant's mastery, it was given to the participants to continue at home. In all referrals and follow-ups, the status of spray use was questioned and participants who did not use it or used it irregularly were excluded from the study.

Clinical and Laboratory Monitoring The required information was taken from the participants' records. The data collection sheet had two sections. In the first part were demographic information and underlying diseases. In the second part, clinical information of research cases was written. Data collection checklist was completed by a trained nurse according to clinical symptoms, para-clinical results, clinical examinations and participant's file contents. Data related to research variables including blood oxygen saturation in pulse oximetry, level of inflammatory factor (CRP), need for adjunctive treatment or readmission in hospital and clinical symptoms in both groups were collected until discharge. The Global Symptomatic Score (GSS) was achieved by calculation of cumulative scores of clinical signs and symptoms including fever, headache, body aches, sore throat, runny nose, chills, cough, shortness of breath, anorexia, loss of smell and loss of taste. Any possible side effects were treated in both groups and reported if present. Participants' oxygenation status was monitored and recorded daily with a pulse oximeter. The pulse oximeter was fixed, and at the time of measurement, the participant was breathing room air without receiving supplemental oxygen.

A modified 7-point ordinal scale was used to assess the clinical condition on day 14 of treatment period related to research. This scale has 7 indexes: