Carotid body dysregulation contributes to Long COVID symptoms.

ABSTRACT

BACKGROUND: The symptoms of long COVID, which include fatigue, breathlessness, dysregulated breathing, and exercise intolerance, have unknown mechanisms. These symptoms are also observed in heart failure and are partially driven by increased sensitivity of the carotid chemoreflex. As the carotid body has an abundance of ACE2 (the cell entry mechanism for SARS-CoV-2), we investigated whether carotid chemoreflex sensitivity was elevated in participants with long COVID. METHODS: Non-hositalised participants with long-COVID (n = 14) and controls (n = 14) completed hypoxic ventilatory response (HVR; the measure of carotid chemoreflex sensitivity) and cardiopulmonary exercise tests. Parametric and normally distributed data were compared using Student's unpaired t-tests or ANOVA. Nonparametric equivalents were used where relevant. Peason's correlation coefficient was used to examine relationships between variables. RESULTS: During cardiopulmonary exercise testing the VE/VCO2 slope (a measure of breathing efficiency) was higher in the long COVID group (37.8 ± 4.4) compared to controls (27.7 ± 4.8, P = 0.0003), indicating excessive hyperventilation. The HVR was increased in long COVID participants (-0.44 ± 0.23 l/min/ SpO2%, R2 = 0.77 ± 0.20) compared to controls (-0.17 ± 0.13 l/min/SpO2%, R2 = 0.54 ± 0.38, P = 0.0007). The HVR correlated with the VE/VCO2 slope (r = -0.53, P = 0.0036), suggesting that excessive hyperventilation may be related to carotid body hypersensitivity. CONCLUSIONS: The carotid chemoreflex is sensitised in long COVID and may explain dysregulated breathing and exercise intolerance in these participants. Tempering carotid body excitability may be a viable treatment option for long COVID patients.

Patients with long COVID suffer from breathlessness during exercise, leading to exercise intolerance. We know that SARS-CoV-2, the virus that causes COVID-19, can infect carotid bodies which is a small sensory organ that sends signals to the brain for regulating breathing and blood pressure. This is called the carotid chemoreflex. However, it is not clear if SARS-CoV-2 infection affects carotid chemoreflex. Here, we examine whether the normal functioning of carotid chemoreflex is disrupted in non-hospitalised patients with long COVID and if this is linked to excessive breathing during exercise. Our study shows that carotid chemoreflex is more sensitive in long COVID patients, who are otherwise healthy. The carotid bodies could be a good therapeutic target for treating breathlessness in patients with long COVID.