# Long-term impacts of COVID-19 on systemic inflammation and control of breathing reflexes: an observational cohort study

## TL;DR

This study shows that recovering from COVID-19 can lead to long-term changes in breathing reflexes and inflammation, which may explain lingering symptoms.

## Contribution

The study reveals a link between systemic inflammation and altered breathing reflexes in long-COVID patients.

## Key findings

- Recovered participants showed a reduced hypercapnic ventilatory response over 24 months.
- Inflammatory markers like SAA and CRP correlated with ventilatory response to hypoxia.
- Six vascular inflammatory markers were lower in recovered participants for up to one year.

## Abstract

The COVID-19 pandemic resulted in over 7 million reported deaths and over 700.4 million reported infections to-date. Many individuals who recover from COVID-19 report prolonged dyspnea, sometimes persisting for months. Furthermore, COVID-19 has been linked to systemic and neuronal inflammation which may have downstream impacts on the neural control of breathing. Therefore, we hypothesized that individuals recovered from COVID-19 may exhibit changes in their ventilatory chemosensitivity to carbon dioxide and hypoxia, and that these changes may be linked to systemic inflammation.

To test this hypothesis, we measured baseline ventilatory patterns and chemoreflex sensitivity in individuals recovered from COVID-19 (n = 77) and individuals with no prior COVID-19 infection (n = 41). Peripheral venous blood samples were also collected for inflammatory biomarker expression and profiling.

Recovered participants demonstrated a small but progressive decrease in the hypercapnic ventilatory response under a co-stimulus with hypoxia (control vs. 24-month post-recovery; p = 0.023). Additionally, we identified several significant correlations between plasma inflammatory markers and ventilatory chemoreflex characteristics, including a positive correlation between SAA and CRP and the ventilatory response to hypoxia (p < 0.05 within recovered and control cohorts). Finally, expression of six vascular inflammatory markers (Myoglobin, NGAL, MMP-2, OPN, IGFBP-4, and Cystatin C) was unexpectedly decreased in recovered participants compared to the control cohort for up to one-year post recovery.

Overall, this data indicates that COVID-19 and other acute viral infections may have a modest impact on the chemoreflex control of breathing as well as systemic inflammatory profiles, and that these changes may be linked to each other. These findings may strengthen our understanding of the pathology of long-COVID symptoms.

The online version contains supplementary material available at 10.1186/s12931-025-03473-6.