The Impact of COVID-19 Infection on Oxygen Homeostasis: A Molecular Perspective

Abstract

The novel coronavirus (2019-nCoV/SARS-CoV-2) causes respiratory symptoms including a substantial pulmonary dysfunction with worsening arterial hypoxemia (low blood oxygenation), eventually leading to acute respiratory distress syndrome (ARDS). The impact of the viral infection on blood oxygenation and other elements of oxygen homeostasis, such as oxygen sensing and respiratory mitochondrial mechanisms, are not well understood. As a step toward understanding these mechanisms in the context of COVID-19, recent experiments revealed contradictory data on the impact of COVID-19 infection on red blood cells (RBCs) oxygenation parameters. However, structural protein damage and membrane lipid remodeling in RBCs from COVID-19 patients that may impact RBC function have been reported. Moreover, COVID-19 infection could potentially disrupt one, if not all, of the other major pathways of homeostasis. Understanding the nature of the crosstalk among normal homeostatic pathways; oxygen carrying, oxygen sensing (i.e., hypoxia inducible factor, HIF) proteins, and the mitochondrial respiratory machinery may provide a target for therapeutic interventions.

Metabolomics analysis identifies glutamic acid and cystine imbalances in COVID-19 patients without comorbid conditions. Implications on redox homeostasis and COVID-19 pathophysiology

“…Leaving aside the metabolic reshaping provoked by the virus on infected cells [ 40 , 41 ], it has been proposed that critical metabolic changes occur in endothelial and immune cells in the early stages of lung damage [ 40 ]. Moreover, if oxygen levels do not recover, the decrement in oxygen supply may lead to further damage to critical organs such as brain, kidneys, and liver [ 42 , 43 ], as observed in critical COVID-19 patients.…”

The Impact of COVID-19 and Muscle Fatigue on Cardiorespiratory Fitness and Running Kinetics in Female Recreational Runners

“…The premature termination of the underperformed running test reflects the physiological impact of the disease in trained individuals. The previously referred impaired blood oxygen transportation in runners from the COVID-19 group might explain the compromised running capacity, in which elevated heart rates and perceived effort can be related to an early transition to anaerobic metabolism ( Alayash, 2021 ; Böning et al, 2021 ). Therefore, our results highlight the significant drop in endurance capacity caused by COVID-19 in recreational runners, with an augmented effort perception caused by the deteriorated physiological status.…”

“…In addition to the fact that these runners presented increased time to reach the peak braking force and increased foot contact time at similar running speed, it is evident that there were adjustments to their motor patterns to run following the COVID-19 hospitalization. Limitations in cardiorespiratory capacity influences muscle activation due to compromised oxygen delivery ( Alayash, 2021 ; Böning et al, 2021 ), potentially influencing runners to achieve optimal running style even in non-fatigued conditions. Since the fatigue protocol was substantially shorter for the recovered runners, no relevant fatigue-related differences in running biomechanics were found.…”

“…Fatigue is multi-factorial, with components related to peripheral muscle contractile function, as well as central factors related to the descending drive to the active muscles ( Bigland-Ritchie et al, 1978 ; Gandevia, 2001 ; Wan et al, 2017 ). It has been suggested that COVID-19 affects oxygen transport to the skeletal muscles ( Alayash, 2021 ; Böning et al, 2021 ), likely influencing the fatigue process. Some of the mechanisms of reduced oxygen availability are 1) the reduced hypercapnia/CO 2 retention that causes “happy hypoxemia” in patients with COVID-19 ( Dhont et al, 2020 ); 2) the infection of O 2 -sensing glomus cells by SARS-CoV-2, which affects central breathing regulation ( Böning et al, 2021 ), and 3) the reduced hemoglobin concentration during the course of COVID-19 ( Liu et al, 2020a ; Kumar et al, 2020 ; Vogel et al, 2020 ).…”

“…Some of the mechanisms of reduced oxygen availability are 1) the reduced hypercapnia/CO 2 retention that causes “happy hypoxemia” in patients with COVID-19 ( Dhont et al, 2020 ); 2) the infection of O 2 -sensing glomus cells by SARS-CoV-2, which affects central breathing regulation ( Böning et al, 2021 ), and 3) the reduced hemoglobin concentration during the course of COVID-19 ( Liu et al, 2020a ; Kumar et al, 2020 ; Vogel et al, 2020 ). Thus, previous SARS-CoV-2 infections might influence essential mechanisms related to oxygen delivery to muscle cells during exercise, potentially accelerating the fatigue process which may lead to early termination of exercise ( Amann and Calbet, 2008 ; Alayash, 2021 ).…”