Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19

Abstract

Objective: Systemic hypoxia occurs in COVID-19 infection; however, it is unknown if cerebral hypoxia occurs in convalescent individuals. We have evidence from other conditions associated with central nervous system inflammation that hypoxia may occur in the brain. If so, hypoxia could reduce the quality of life and brain function. This study was undertaken to assess if brain hypoxia occurs in individuals after recovery from acute COVID-19 infection and if this hypoxia is associated with neurocognitive impairment and reduced quality of life.

Methods: Using frequency-domain near-infrared spectroscopy (fdNIRS), we measured cerebral tissue oxygen saturation (S_tO₂) (a measure of hypoxia) in participants who had contracted COVID-19 at least 8 weeks prior to the study visit and healthy controls. We also conducted neuropsychological assessments and health-related quality of life assessments, fatigue, and depression.

Results: Fifty-six percent of the post-COVID-19 participants self-reported having persistent symptoms (from a list of 18), with the most reported symptom being fatigue and brain fog. There was a gradation in the decrease of oxyhemoglobin between controls, and normoxic and hypoxic post-COVID-19 groups (31.7 ± 8.3 μM, 27.8 ± 7.0 μM and 21.1 ± 7.2 μM, respectively, p = 0.028, p = 0.005, and p = 0.081). We detected that 24% of convalescent individuals' post-COVID-19 infection had reduced S_tO₂ in the brain and that this relates to reduced neurological function and quality of life.

Interpretation: We believe that the hypoxia reported here will have health consequences for these individuals, and this is reflected in the correlation of hypoxia with greater symptomology. With the fdNIRS technology, combined with neuropsychological assessment, we may be able to identify individuals at risk of hypoxia-related symptomology and target individuals that are likely to respond to treatments aimed at improving cerebral oxygenation.

Keywords: Brain hypoxia; Cerebral hypoxia; Cerebral tissue Oxygen saturation; Frequency-domain near-infrared spectroscopy; Post-COVID-19 condition.

Fig. 1

Frequency-domain near-infrared spectroscopy (ISS OxiplexTS, model 96,208, ISS Inc., Champaign, IL) used in the measurement of frontal cortical microvascular oxygenation (S_tO₂)

Fig. 2

fdNIRS measurement of cortical microvascular oxygenation (S_tO₂) in healthy controls and all post-COVID-19 participants, showing the data distribution. Each dot represents one participant. Green shaded area represents 2 ± SD around the control mean. All points below the shaded area are 2 × SD below the controls (classed as hypoxic)

Fig. 3

Correlation analysis between S_tO₂ (%), age (years) and total hemoglobin (THb (μM)), and months since infection, analyzed for all participants

Fig. 4

Correlation analysis between S_tO₂ (%) and paced auditory serial addition (PASAT) for healthy controls and all post-COVID-19 participants (A), health-related quality of life measure (physical functioning (B), role limitation-physical (C), energy/fatigue (D) and social functioning (E)), measure of fatigue (FACIT-F) (F) and measure of depression (BDI-II) (G) measured in post-COVID-19 participants only