Intrapulmonary shunting is a key contributor to hypoxia in COVID-19: An update on the pathophysiology

BACKGROUND: The pathophysiology of COVID-19 remains poorly understood. We aimed to estimate the contribution of intrapulmonary shunting and ventilation-to-perfusion (V(A)/Q) mismatch using a mathematical model to construct oxygen-haemoglobin dissociation curves (ODCs). METHODS: ODCs were constructed using transcutaneous pulse oximetry at two different fractions of inspired oxygen (FiO(2)). 199 patients were included from two large district general hospitals in the South East of England from 1(st) to 14(th) January 2021. The study was supported by the National Institute of Health Research (NIHR) Clinical Research Network. RESULTS: Overall mortality was 29%. Mean age was 68.2 years (SEM 1·2) with 46% female. Median shunt on admission was 17% (IQR 8–24.5); V(A)/Q was 0.61 (IQR 0.52–0.73). Shunt was 37.5% higher in deaths (median 22%, IQR 9–29) compared to survivors (16%, 8–21; p = 0.0088) and was a predictor of mortality (OR 1.04; 95% CI 1.01–1.07). Admission oxygen saturations were more strongly predictive of mortality (OR 0.91, 95% CI 0.87–0.96). There was no difference in V(A)/Q mismatch between deaths (0.60; IQR 0.50–0.73) and survivors (0.61; IQR 0.52–0.73; p = 0.63) and it was not predictive of mortality (OR 0.68; 95% CI 0.18–2.52; p = 0.55). Shunt negatively correlated with admission oxygen saturation (R -0.533; p<0.0001) whereas V(A)/Q was not (R 0.1137; p = 0.12). INTERPRETATION: Shunt, not V(A)/Q mismatch, was associated with worsening hypoxia, though calculating shunt was not of prognostic value. This study adds to our understanding of the pathophysiology of hypoxaemia in COVID-19. Our inexpensive and reliable technique may provide further insights into the pathophysiology of hypoxia in other respiratory diseases.