Cellular Immuno-Therapy for COVID-19 Induced Acute Respiratory Distress Syndrome: the CIRCA-19 Trial [Added supplement: COVID-19 Variant Supplement]

The number of patients with the novel COVID-19 disease continues to rise world-wide. Approximately 20% of patients require hospitalization, and up to a quarter of these need intensive medical care, mainly due to intense inflammation (swelling) of the lung called 'acute respiratory distress syndrome' or ARDS. This interferes with the lung's ability to exchange oxygen, requiring a machine to support their breathing called a ventilator. Unfortunately, about half of patients who need a ventilator because of COVID-19 lung disease will not survive. We have no specific therapy to treat the lung swelling in these patients. Mesenchymal stromal cells, often termed 'MSCs', have anti-inflammatory effects that can reduce lung swelling in animal models of ARDS. As well, therapy with MSCs in humans has been shown to be safe, with some promising results in patients with severe inflammation due to uncontrolled infections as well as lung swelling due to ARDS. The few small clinical studies using MSCs to treat COVID-19 patients were not properly designed to assess the benefit of MSC therapy. The proposed Cellular Immuno-Therapy for COVID-19 related ARDS (CIRCA-19) trial is a randomized and placebo-controlled study designed to test whether giving MSCs to patients with severe lung swelling due to COVID-19 disease will decrease the need for a ventilator and whether this novel therapy will also have other important benefits such as improving survival and reducing the injury to vital organs like the heart, lungs and kidneys. The MSCs will be obtained from umbilical cords that are harvested during Caesarian section, and then grown in a specially equipped clinical-grade cell manufacturing facility at The Ottawa Hospital using Health Canada approved processes. We have rapidly deployed a multidisciplinary team and have already submitted the study to both Health Canada and Research Ethics for approvals, and we anticipate treating our first patient in early June 2020.