Links between systemic inflammation and the chemoreflex control of breathing following COVID-19

Abstract

The emergence of SARS-CoV-2 resulted in millions of hospitalizations and 6.9 million deaths to-date. Many individuals who recover from COVID-19 report prolonged dyspnea, with this symptom persisting for months following recovery. Furthermore, data suggests COVID-19 has been linked to systemic and neuronal inflammation which may have downstream impacts on the neural control of breathing. As such, we hypothesized that individuals recovered from COVID-19 may exhibit changes in their ventilatory chemosensitivity to CO2 and/or O2 and that these changes may be linked to higher levels of systemic inflammation. To test this hypothesis, we measured baseline ventilatory patterns and chemoreflex sensitivity using a modified rebreathing technique in individuals recovered from COVID-19 (n = 77), as well as an age and sex-matched control group (n = 41). Peripheral blood samples were also collected for inflammatory profiling. Recovered participants demonstrated lower ventilatory responses to hypercapnia, particularly under a combined hypoxic stimulus (p = 0.032). Furthermore, higher levels of plasma IL-1β and IL-6 were associated with lower hypoxic ventilatory responses (R2 = -0.53, p = 0.025; R2 = -0.49, p = 0.04), highlighting a potential link between systemic inflammation and ventilatory chemoreflex sensitivity. When separated by time-post-recovery, we observed a decreased ventilatory recruitment threshold (VRT) beginning at 4 months post-recovery (p = 0.019) that returned to baseline after one-year post-recovery. A decrease in sensitivity to CO2 was also noted immediately after recovery with no return to baseline observed within the two-year tested time frame (p = 0.023). Overall, this data indicates that (1) COVID-19 may have impacts on the neural control of breathing, and (2) systemic inflammation may play a role in modulating ventilatory chemoreflex sensitivity. These findings may have implications for the pathology of long-COVID symptoms, including sleep disturbance and prolonged dyspnea. This work was funded by the Health Disparities Research Center and the OASIS center at University of California, Riverside. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.