A Randomized Phase 2 Dose Ranging, Active Control Trial of Using a Sequential Rebreathing Oxygen Mask (Hi-OxSR) to Increase PCO2 for the Treatment of Post COVID Cognitive Dysfunction (RECLAIM-Hi-OxSR)

Increasing numbers of Canadians are presenting with long COVID, with fatigue and cognitive impairment among the most common symptoms. A conservative estimate of ~15% of those infected with SARS-CoV-2 would result in over 100 million people with long COVID globally, urgently in need of treatment. Our phase 1 pilot study examining the use of re-breathing CO2 (using HiOxSR) in patients with long COVID showed significant improvements in cognitive function. We propose to build on these findings and implement a phase 2 randomized trial to determine the optimal effective dose (i.e. duration) of treatment of using HiOxSR in this patient population. We will use our national CIHR funded RECLAIM (REcovering from COVID19 Lingering symptoms Adaptive Integrative Medicine) platform to run this trial. Inclusion criteria: age > 18 with lingering symptoms over 3 months from acute COVID-19 illness that cannot be explained by an alternative diagnosis. Exclusion criteria: currently hospitalized for COVID-19, physician diagnosed cognitive dysfunction prior to COVID infection, investigational drug use within 30 days, pregnant or breastfeeding, history of pulmonary hypertension, interstitial pulmonary fibrosis, moderate to severe COPD, history of narcolepsy, any condition that would compromise safety or data quality. 120 participants will be randomized to 3 groups: Group 1-use of Hi-OxSR for 2 weeks, Group 2-use of Hi-OxSR for 4 weeks, or Group 3 (active control group)-2 weeks using same oxygen mask at high oxygen flow (5L/min) which prevents rebreathing. Assessments: baseline, 2 weeks, 4 weeks, 8 weeks. Dual Primary Outcomes: 'choice reaction time' and 'verbal paired associates' results from the TestMyBrain neuropsychology toolkit, measured at 2 months. Secondary Outcomes: cognitive function, fatigue, health related quality of life, safety. This innovative trial has high potential to support the development and commercialization of a new treatment to respond to an urgent health challenge.