Efficacy and Safety of Inhaled Ethanol in Early-Stage SARS-CoV-2 Infection in Older Adults: A Phase II Randomized Clinical Trial

Abstract

Background: Inhaled ethanol in the early stages of SARS-CoV-2 infection may reduce the viral load, decreasing progression and improving prognosis. The ALCOVID-19 trial was designed to study the efficacy and safety of inhaled ethanol in older adults at initial phases of infection. Methods: Randomized, triple-blind, placebo-controlled phase II clinical trial. Experimental group (n = 38) inhaled 65° ethanol through an oxygen flow, while in the control group (n = 37), water for injection was used. General endpoint was to evaluate disease progression according to the modified World Health Organization (WHO) Clinical Progression Scale. Specific effectiveness endpoints were body temperature, oxygen saturation, viral load assessed by cycle threshold (Ct) on real-time polymerase chain reaction (RT-PCR), analytical biomarkers and use of antibiotics or corticosteroids. Specific safety outcomes were the absence of ethanol in plasma, electrographic, analytical, or respiratory alterations. Results: In the intention-to-treat population, no differences were found regarding disease progression. Mean Ct values increased over time in both groups, being numerically higher in the ethanol group, reaching a value above 33 only in the ethanol group on day 14, a value above which patients are considered non-infective. No differences were found in the other specific effectiveness endpoints. Inhaled ethanol was proven to be safe as no plasma ethanol was detected, and there were no electrocardiographic, analytical, or respiratory alterations. Conclusions: The efficacy of inhaled ethanol in terms of the progression of SARS-CoV-2 infection was not demonstrated in the present trial. However, it is positioned as a safe treatment for elderly patients with early-stage COVID-19.

Positive Correlation Between Heavy Alcoholic Drinking and SARS-Cov-2 Non-Infection Rate

“…Notably, neither the treated animals nor the controls' histology samples showed any signs of damage. A recent randomized controlled trial (RCT) from the same group has confirmed these data in humans [ 12 ].…”

“…Now, if this might have been acceptable in 2020, at present, the evidence showed by Pro et al [ 8 ] should lead to a selective update, at least. Particularly, the RCT from the Spanish group [ 12 ] found a faster and higher - even not significative - reduction of the viral load in the EtOH-treated patient's group versus controls. Unfortunately, the RCT had to be ended earlier for insufficient recruitment.…”

“…In summary, except for the well-known negative effect of alcohol on human health in general, to our knowledge, the correlation between liquor drinking and the rate of infection (or not-infection) of SARS-Cov-2 has not been studied seriously. On the other hand, some reports elucidated the theoretical bases of the EtOH efficacy in eradicating the SARS-Cov-2 from airways [ 9 ], the efficacy in preventing infection [ 10 ], and improving COVID-19 outcomes [ 11 , 12 ]. With the end of the dynamic zero-COVID policy in China on Dec 7, 2022, a tide of infection emerged, and the number of people infected with SARS-Cov-2 increased rapidly in China in January 2023.…”

Ethanol Inhalation in Treatment and Prevention of Coronavirus Disease (COVID-19)

“…Methanol poisoning [11], fat embolism [12], premature labor prevention [13], preeclampsia [14], and pulmonary edema [15] have all been treated with ethanol-specific treatments in the past. Castro-Balado et al [16] have shown the histological safety of inhalation ethanol treatment on rats' lungs and respiratory systems. Ethanol was authorized by the Food and Drug Administration.…”

“…A lot of concern has been expressed regarding the potential mucosal harm that breathed ethanol might cause. Castro-Balado et al careful research[16] appears to have completely dispelled these concerns. It should be noted that spraying into the mask prolongs the action of the nebulized liquid and maintains its efficiency by reducing the dispersion and evaporation of the liquid.…”