Evaluation of blood levels of cytokines, caspase-1 and NETs in patients with moderate and severe forms of COVID-19 treated with standard therapy plus placebo or colchicine

Abstract

2019 Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major health problem worldwide. The most frequent clinical manifestations include fever, cough, fatigue, sputum, dyspnoea, pain in the oropharynx and headache. Elderly and individuals with chronic diseases are the group most at risk for moderate and severe forms of the disease and for the development of acute respiratory distress syndrome (ARDS). The diagnosis is based on epidemiology, presence of fever and respiratory symptoms, image examination of the lungs (infiltrated in ground glass on computed tomography) and detection of viral RNA by RT-PCR (polymerase chain reaction with reverse transcriptase) in secretions of the airways. There is no specific treatment for COVID-19 disease, which is supportive when patients have pneumonia requiring hospitalization. We showed, in a double-blind, placebo-controlled clinical trial, that the use of colchicine in cases of moderate and severe COVID-19 led to a reduction in the duration of supplemental oxygen therapy and a reduction in the length of hospital stay, without the occurrence of serious adverse events. Goals. To quantify cytokines, caspase-1 and NET products in the blood of patients with COVID-19 at admission and during evolution. To assess whether there is a correlation between blood levels of cytokines and NETs and general clinical and laboratory parameters in patients with COVID-19 treated or not with colchicine. To evaluate whether the quantification of cytokines and/or NETs can be a predictor of response to treatment with colchicine in the moderate and severe forms of COVID-19. Patients and methods. We will proceed with the quantification of cytokines, caspase-1 and NETs in biological material obtained from 100 participants in a randomized clinical study, with 1:1 allocation in two groups: standard treatment plus placebo (control group, n=50) versus standard treatment plus colchicine (colchicine group, n=50). Patients in the colchicine group will receive medication at a dose of 0.015-0.033 mg / kg / day for 5 days, followed by 0.012-0.020 mg / kg / day for 5 days, for a total of 10 days. The evaluation of cytokines, extracellular caspases and NETs will be performed on admission and on days 2 or 3, 5, 7, 10 and 14 of hospitalization. (AU)