The potential role of the carotid body in COVID-19

Abstract

The carotid body (CB) plays a contributory role in the pathogenesis of various respiratory, cardiovascular, renal and metabolic diseases, through reflex changes in ventilation and sympathetic output. On the basis of available data about peripheral arterial chemoreception and Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV2), a potential involvement in the Coronavirus Disease 2019 (COVID-19) may be hypothesized through different mechanisms. The CB could be a site of SARS-CoV2 invasion, due to local expression of its receptor (Angiotensin-Converting Enzyme (ACE) 2), and an alternative route of nervous system invasion, through retrograde transport along the carotid sinus nerve. The CB function could be affected by COVID-19-induced inflammatory/immune reactions and/or ACE1/ACE2 imbalance, both at local or systemic level. Increased peripheral arterial chemosensitivity and reflex sympatho-activation may contribute to the increased morbidity/mortality in COVID-19 patients with respiratory, cardiovascular, renal or metabolic comorbidities.

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

“…Given the low partial pressure of oxygen in arterial blood (PaO 2 ) of patients infected with SARS-CoV-2 virus ( Sartini et al, 2020 ; Chen et al, 2020 ), the carotid bodies and the resulting reflex responses are likely to play a central role in the symptoms and outcomes ( Porzionato et al, 2020a , Porzionato et al, 2020b ; Holmes, 2020 ). Hence, our focus will be related to the involvement of this sensory system across COVID patients expressing distinct disease characteristics and including differing age, gender, co-morbidities and genetic backgrounds ( Tobin et al, 2020 ).…”

“…Further, its sensitivity may be changed by a SARS-CoV-2 infection and this could be either sensitisation or de-sensitisation as we discuss below. In this regard, Gattinoni et al (2020) and Porzionato et al, 2020a , Porzionato et al, 2020b report each COVID-19 patient has an exclusive finger print and an unpredictable combination of multiple factors that determine the course of the infection and symptoms experienced. Thus, such factors will affect an individual's response profile to hypoxia this may determine the degree of involvement of carotid body activation in COVID-19 patients affecting their response to the disease and their outcome.…”

“…Thus, such factors will affect an individual's response profile to hypoxia this may determine the degree of involvement of carotid body activation in COVID-19 patients affecting their response to the disease and their outcome. We recognise that the carotid bodies are not solely sensors of blood gases but are multi-modal arterial sensors responding to inflammation, low blood pressure, sympathetic activity and a variety of metabolically related hormones, so their involvement may well go beyond responding to hypoxia in COVID-19 patients ( De Burgh Daly, 1997 ; Iturriaga et al, 2015 ; Zera et al, 2019 ; Porzionato et al, 2020a , Porzionato et al, 2020b ; Gattinoni et al, 2020 ; Tobin et al, 2020 ; Holmes et al, 2019 ; Holmes, 2020 ).…”

“…1 ). Based on predominance of evidence, we will focus on the changes in sensitivity of the carotid body and to a lesser extent on alterations in down stream synaptic processing as this scenario is known to cause respiratory, cardiovascular and autonomic dysregulation during hypoxia ( Porzionato et al, 2020a , Porzionato et al, 2020b ; Gattinoni et al, 2020 ; Chen et al, 2020 ; Archer et al, 2020 ). In this regard, we compare the effects of high altitude on the carotid body and their relevance to potential mechanisms and symptoms expressed in COVID-19 patients.…”

“…The severity and prevalence of SARS-CoV-2 infection appears highest in older males and those with co-morbidities such as hypertension, heart failure, obesity and diabetes ( Guzik et al, 2020 ). In all these clinical conditions, increased carotid body excitability has been found ( Porzionato et al, 2020a , Porzionato et al, 2020b ). [Note: we use the term excitability to describe both reflex sensitivity (e.g.…”