Introduction

Long-COVID is a debilitating condition in which people continue to have health problems for months or years following COVID-19 infection. Long-COVID affects nearly 2 million people in the UK and costs ~£5.7 billion per year in productivity loss^[1]. Many people with long-COVID experience ongoing breathing difficulties, despite having normal lung function and no evidence of gas exchange abnormalities. Evidence indicates that patients with long-COVID, who were not hospitalised for their initial infection, experience hyperventilation at rest and during exercise. The carotid chemoreflex plays an important role in the control of breathing at rest and during exercise^[2] and its sensitivity was recently shown to be increased in people with long-COVID^[3]. However, whether this hypersensitive carotid chemoreflex drives some of the hyperventilation experienced by patients with long-COVID remains unknown. Dopamine is used to inhibit carotid body afferent discharge into the brainstem, which inhibits the carotid chemoreflex response to hypoxia. However, some evidence suggests that dopamine signalling may be impacted in patients with long-COVID^[4]. Thus, whether dopamine inhibits the carotid chemoreflex in patients with long-COVID is also unclear.

Objective

Dopamine will reduce carotid chemoreflex sensitivity in response to hypoxia and improve hyperventilation at rest in people with long-COVID, versus saline.

To determine whether inhibiting the carotid chemoreflex with low-dose dopamine can reduce heightened carotid chemoreflex sensitivity during hypoxia in people with long-COVID and improve their hyperventilation at rest.

Hypothesis

Methods

Six (2M, 4F, age; 50±9 years, BMI; 29.6±3.2 kg/m²) participants with long-COVID completed resting ventilation measurements (during normoxia) and hypoxic ventilatory response (HVR) testing (measure of carotid chemoreflex sensitivity) during intravenous infusion of low-dose dopamine (2 mcg/kg/min) or saline (control) at rest. HVR was evaluated as the slope of the linear regression relating the minute ventilation to the nadir of oxygen saturation for each nitrogen exposure. Data were compared using Wilcoxon matched-pairs rank test. Data are reported as median (IQR).

Results

Intravenous dopamine reduced carotid chemoreflex sensitivity to hypoxia in people with long-COVID compared to saline (-0.15 (-0.17 to -0.09) L/min/SpO₂% versus -0.36 (-0.79 to -0.20) L/min/SpO₂%, P=0.0312, Cohen’s D=1.061). Resting partial pressure of the end-tidal CO₂ (P_ETCO₂) tended to be increased with dopamine compared to saline (43 (41-44) mmHg versus 40 (38-42) mmHg), P=0.0312, Cohen’s D=1.5), indicating a reduction in excessive hyperventilation at rest with dopamine.

Conclusion

Inhibiting the carotid chemoreflex with low-dose dopamine normalised HVR and improved hyperventilation at rest in people with long-COVID, versus saline. Tempering the carotid chemoreflex may be a viable treatment for people with long-COVID and unexplained dysregulation of ventilation.