Tuesday, April 23, 2024
4/23/2024
Abstract The severe acute respiratory syndrome coronavirus 2, which causes the highly contagious coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. COVID-19 cases in the New York City (NYC) tri-state area continue to rise exponentially and the region is now the epicenter of the crisis in the United States. In NYC alone, there are over 21,000 cases (~40% =40 years of age) as of March 26, 2020. Many symptomatic COVID-19 patients have features of a cytokine storm and/or macrophage activation syndrome, including elevated levels of interleukin (IL)-6. An overly robust local neutrophil influx may also contribute to the robust immune response with associated severe cardiopulmonary complications, including acute respiratory distress syndrome requiring mechanical ventilation and myocarditis with cardiogenic shock. Colchicine is a safe, well- tolerated anti-inflammatory agent that suppresses the activation of the NLRP3 inflammasome, thereby blocking conversion of pro-IL-1ß to active IL-1ß, which leads to secondary reductions in other cytokines including IL-6 along with inhibition of macrophage activation. Colchicine also preferentially accumulates in neutrophils compared with other inflammatory cells and inhibits chemotaxis, endothelial adhesion, and extravasation of neutrophils at sites of endothelial or tissue inflammation. The effects of colchicine in preventing the cytokine storm and/or macrophage activation syndrome that leads to clinical deterioration in COVID-19, however, is not known. Colchicine is not known to inhibit acquired immunity, and is not contraindicated in patients with infection. The COLCORONA study is a Canadian government-funded randomized trial of colchicine vs. placebo for 30 days in 6,000 non-hospitalized subjects ¿40 years of age with COVID-19 diagnosis and at least one high-risk criterion. This proposal leverages the COLCORONA Trial infrastructure and pragmatic study design with virtual consent, randomization, and follow-up to rapidly implement the COLCORONA-NYC Study and allow potential eligible subjects in the NYC tri-state area to participate. The overall aim of the study is to determine the effect of colchicine on the composite of death or the need for hospitalization in non-hospitalized adults with COVID- 19. The data collected through the COLCORONA-NYC study will provide novel data on treatment of COVID-19 patients, and have public health implications beyond the scope of the current application, including the potential reduction in the healthcare resources heavily used in COVID-19 (e.g., hospital beds, ventilators), and potential future use in other infectious causes of acute respiratory distress syndrome.
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