Relevance of carotid bodies in COVID-19: A hypothetical viewpoint

Abstract

We have considered some of the available evidence to account for the impact of SARS-CoV on the regulatory control of the autonomic nervous and respiratory systems. Apart from stimulating general interest in the subject, our hope was to provide putative explanations for some of the patients' symptoms based on described physiological and pathophysiological mechanisms seen in other diseases. Herein, we have focused on the carotid bodies. In this hypothetical viewpoint, we have discussed the plasticity of the carotid body chemoreflex and made a comparison between acute and chronic exposures to high altitude with COVID-19. From these discussions, we have postulated that the sensitivity of the hypoxic ventilatory response may well determine the outcome of disease severity and those that live at high altitude may be more resistant. We have provided insight into silent hypoxia and attempted to explain an absence of ventilatory drive and anxiety yet maintenance of consciousness. In an attempt to discover more about the mysteries of COVID-19, we conclude with questions and some hypothetical studies that may answer them.

Keywords: Cerebral blood flow; Chemoreflexes; High altitude; Hypoxic ventilatory response; SARS-CoV.

Fig. 1

Schematic drawing of the peripheral chemoreflex pathways in the brainstem and representing the different profile of carotid body in COVID-19 patients: Carotid Body A) in the majority of patients the carotid body reflex responds very well to the hypoxic challenge and the glomus cells are not infected by SARS-CoV-2; Carotid Body B) in a small percentage of patients the carotid bodies may be overactive even before the SARS-CoV-2 infection or became overactive as consequence of the acute phase of the infection; and Carotid Body C) in a smaller percentage of the population the carotid bodies are de-sensitised or non functional even before the SARS-CoV-2 infection or glomus cells were killed after the infection (Villadiego et al., 2021). We also acknowledge infection of SARS-CoV-2 in the brainstem (Bulfamante et al., 2020) and because of the loss of taste (ageusia), we cannot rule out within the petrosal ganglion (e.g. Gautier and Ravussin, 2020); both these loci could affect chemoreflex function.

Fig. 2

Schematic to summarise the interactions of respiratory blood gases and chemoreceptor (peripheral and central) ventilatory drive in the condition of COVID-19 induced silent hypoxia. For details see text. Note, the recent finding of Lambermont et al. (2021) is consistent with infection of the carotid body itself via ACE2, which expression is high in the carotid body of humans (Villadiego et al., 2021).