Persistent exertional dyspnea following mild COVID-19: potential association with diaphragm impairment

Background Persistent exertional dyspnea is a common symptom in long COVID, and routine cardiopulmonary testing is often unrevealing. The underlying mechanisms remain incompletely understood. Although exertional dyspnea has been linked to diaphragm weakness among hospitalized individuals, studies using state-of-the-art respiratory muscle assessment in non-hospitalized cohorts are lacking. Objective This study investigated the role of respiratory muscle function in exertional dyspnea in non-hospitalized patients after mild COVID-19 infection. Methods 25 outpatients with persistent dyspnea were assessed at a median 24 months after mild COVID-19 infection. Evaluations included pulmonary function testing, 6-minute walk test, echocardiography, twitch transdiaphragmatic pressure (TwPdi) following cervical magnetic stimulation of the phrenic nerve roots, and diaphragm ultrasound. Diaphragm parameters were compared with those of a healthy control group (3:1 matched for age, sex, BMI, and comorbidities). Main results Routine blood results, pulmonary function testing or echocardiography showed no clear alternative explanation for dyspnea at the group level. However, COVID-19 individuals exhibited significantly lower diaphragm strength (expressed in TwPdi) than controls (p=0.02), with results varying across dyspnea subgroups (overall ANOVA p-value = 0.009). A negative correlation was observed between TwPdi and dyspnea expressed on mBorg scale (r = -0.67, 95% CI -0.84 to -0.37, p < 0.001). Signs indicating potential structural alterations were observed in post-COVID patients, with significantly reduced diaphragm thickness at functional residual capacity (FRC) and total lung capacity (TLC) compared to controls (p = 0.02 and p < 0.001). Conclusions Persistent exertional dyspnea after mild COVID-19 is associated with diaphragm weakness and structural changes despite normal cardiopulmonary findings, supporting a key role for respiratory muscle impairment as a potential contributor to dyspnea in long COVID despite initial mild infection.