Carotid body dysregulation contributes to Long COVID symptoms

Ahmed El-Medany, Zoe H Adams, Hazel C Blythe, Katrina A Hope, Adrian H Kendrick, Ana Paula Abdala Sheikh, Julian F. R. Paton, Angus K Nightingale, Emma C J Hart*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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.
Original languageEnglish
Article number20
JournalCommunications Medicine
Volume4
Issue number1
DOIs
Publication statusPublished - 19 Feb 2024

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