A prospective, open label, randomized, crossover, pilot, exploratory study to describe the effect of the Inogen One® G4 POC on brain hypoxia, peripheral oxygen saturation and cognitive function in adults with longterm- COVID.

After a 2-week screening/baseline evaluation, participants will be randomized in a 1:1 allocation ratio to one of the following 2 sequences: 1) portable oxygen concentrator (POC) for a first 2-week period followed by standard of care (SOC) for a second 2-week period or 2) SOC for a first 2-week period followed by POC for a second 2-week period. There will be a washout period of one week between the two treatment periods. A total of 10 subjects will be enrolled per sequence.

Inclusion Criteria:

1. Ability and willingness to give written informed consent prior to any study-specific screening procedures and to comply with the requirements of the study
2. Male or female, aged ≥ 18 years of age
3. Diagnosed with Long-COVID
4. Patient self-reported concerns regarding cognitive functioning or recent diagnosis of COVID-19 related cognitive impairment
5. MoCA test scores ranging from 13 to 25/30 at screening
6. Oxygen saturation SpO2 ≤ 93 % on fingertip pulse oximetry and/or < 60% on brain NIRS, at rest or during effort and/ or 10% relative decrease in brain saturation during exercise as compared to baseline value at screening
7. Ability to perform exercise treadmill test at screening
8. Tolerability of pulsed oxygen (O2) therapy delivered by POC at screening
9. Willingness and ability to wear POC.

Exclusion Criteria:

1. Contraindication to the use of POC including allergy to cannula material
2. Pregnancy or planning to become pregnant during the study
3. Non-COVID-related cause for cognitive impairment (such as Parkinson's disease, multiple sclerosis, Alzheimer's disease, stroke, brain tumor, or dementia)
4. Subjects with respiratory infection at screening or randomization and/or acute bronchitis requiring antibiotics at the time of randomization or expected during the treatment
5. Participation in other interventional clinical trial within 30 days of randomization or expect to participate in any other investigational clinical trial during the conduct of this trial
6. Subjects who should be excluded in the opinion of the investigator