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Assessment of chemoreflex control of respiratory and cardiovascular systems in Post-COVID-19 syndrome

Chief Investigator

Institution

Dates

Funding Stream

Amount
Dr Ahmed El- Medany

University of Bristol

01/11/2021 to 31/12/2023

Above and Beyond Spring 2021

 £9,140

Summary

Around 4 million individuals have tested positive for COVID-19 in the United Kingdom (UK) up to February 2021. Some people who have recovered from the immediate effects of COVID-19 describe ongoing symptoms including poor exercise tolerance, fatigue, chest pain, inappropriate increases in heart rate when standing and dizziness, which are common symptoms of 'Post-COVID-19 Syndrome' (sometimes termed long COVID-19). These symptoms typically last for more than 12 weeks and can be severely debilitating. Currently, we do not know why people develop post-COVID-19 syndrome; understanding the causes underlying it could help us develop new therapies to help people recover. Following COVID-19 infection, evidence shows that multiple systems in the body may drive post COVID-19 syndrome; including the brain and poor function of parts of the nervous system that control heart rate and blood pressure.
The carotid body, a small organ in the carotid arteries (blood vessels in your neck - where your pulse can be found), monitors oxygen levels in the blood and keeps tight control over breathing, heart rate, and blood pressure. This organ has a high amount of an enzyme by which coronavirus enters the cells and causes infection. The carotid body is also sensitive to inflammation, which is triggered by local infection. It is possible that infection of the carotid body by coronavirus, and the inflammation that happens after the infection, drives ongoing symptoms such as breathlessness, inappropriate increases in heart rate, and dizziness in people experiencing post-COVID-19 syndrome.
The aim of this study is to investigate whether the carotid body is involved in the development of post-COVID-19 syndrome in men and women.

Progress to date 

  1. Completion of participant recruitment and study visits Jan '23
  2. Manuscript completed and submitted to Nature Communications Medicine - currently under revision June '23
  3. MRC grant proposal submitted - second submission underway following MRC panel comment (deadline Oct '23)

Main findings

  1. Here we show for the first time that carotid chemoreflex sensitivity is amplified in non-hospitalised patients with post-COVID-19 syndrome, versus a control group
  2. This carotid chemoreflex hypersensitivity correlates with hyperventilation and poor breathing efficiency during exercise
  3. Elevated carotid chemoreflex sensitivity could explain several of the ongoing symptoms experienced by patients living with post-COVID-19 syndrome

Impact

Interventions that temper carotid body excitability could be explored as a treatment option for post-COVID-19 syndrome. Previously our group had shown that P2X3 receptors in the carotid body can be targeted to reduce carotid chemoreflex hyperreflexia in an animal model of hypertension and heart failure and could be a viable target in humans with post-COVID-19 syndrome. Gefapixant, an oral P2X3 receptor antagonist, has recently demonstrated efficacy and an acceptable safety profile in chronic cough in phase 3 clinical trials. P2X3 receptors could therefore be a viable target in humans with post-COVID-19 syndrome.

Project outputs 

International presentations

1.       ASSESSMENT OF PERIPHERAL CHEMOREFLEX CONTROL OF RESPIRATORY AND CARDIOVASCULAR SYSTEMS IN POST-COVID-19 SYNDROME

Live virtual presentation at the Physiological Society Long COVID: Mechanisms, Risk Factors, and Recovery online conference 2022

2.       ASSESSMENT OF VENTILATORY EFFICIENCY USING CARDIOPULMONARY EXERCISE TESTING IN POST-COVID-19 SYNDROME

Live virtual presentation at the Physiological Society Long COVID: Mechanisms, Risk Factors, and Recovery online conference 2022

THE ROLE OF THE PERIPHERAL CHEMORECEPTOR REFLEX IN NON-HOSPITALISED PATIENTS WITH POST-COVID-19 SYNDROME

Live moderated poster presentation at the European Society of Cardiology congress 2023 (August 2023)

  Publications

1.       CAROTID BODY DYSREGULATION CONTRIBUTES TO THE ENIGMA OF LONG COVID

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

doi:  https://doi.org/10.1101/2023.05.25.23290513