Dyspneic and non-dyspneic (silent) hypoxemia in COVID-19: Possible neurological mechanism

Masoud Nouri-Vaskeh, Ali Sharifi, Neda Khalili, Ramin Zand, Akbar Sharifi, Masoud Nouri-Vaskeh, Ali Sharifi, Neda Khalili, Ramin Zand, Akbar Sharifi

Abstract

SARS-CoV-2 mainly invades respiratory epithelial cells by adhesion to angiotensin-converting enzyme 2 (ACE-2) and thus, infected patients may develop mild to severe inflammatory responses and acute lung injury. Afferent impulses that result from the stimulation of pulmonary mechano-chemoreceptors, peripheral and central chemoreceptors by inflammatory cytokines are conducted to the brainstem. Integration and processing of these input signals occur within the central nervous system, especially in the limbic system and sensorimotor cortex, and importantly feedback regulation exists between O2, CO2, and blood pH. Despite the intensity of hypoxemia in COVID-19, the intensity of dyspnea sensation is inappropriate to the degree of hypoxemia in some patients (silent hypoxemia). We hypothesize that SARS-CoV-2 may cause neuronal damage in the corticolimbic network and subsequently alter the perception of dyspnea and the control of respiration. SARS-CoV-2 neuronal infection may change the secretion of numerous endogenous neuropeptides or neurotransmitters that distribute through large areas of the nervous system to produce cellular and perceptual effects. SARS-CoV-2 mainly enter to CNS via direct (neuronal and hematologic route) and indirect route. We theorize that SARS-CoV-2 infection-induced neuronal cell damage and may change the balance of endogenous neuropeptides or neurotransmitters that distribute through large areas of the nervous system to produce cellular and perceptual effects. Thus, SARS-CoV-2-associated neuronal damage may influence the control of respiration by interacting in neuromodulation. This would open up possible lines of study for the progress in the central mechanism of COVID-19-induced hypoxia. Future research is desirable to confirm or disprove such a hypothesis.

Keywords: COVID-19; Central Nervous System; Hypoxemia; Neural Invasion; SARS-CoV-2.

Copyright © 2020 Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
A neurobiological model framework shows the route of entry of SARS-CoV-2 via the systemic circulation and olfactory bulb to the brain. Afferent impulses from chemoreceptors and mechanoreceptors are transmitted to the brainstem, limbic system, and cerebral cortex for integration and processing. The central nervous system directs efferent motor commands via the phrenic and thoracic spinal nerves to regulate ventilation and modify dyspnea.
Fig. 2
Fig. 2
Potential mechanisms of central nervous system involvement by SARS-CoV-2.

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