Diaphragm Muscle Weakness related Dyspnea Persists Two Years After COVID-19 and can be Improved by Inspiratory Muscle Training

Rationale: Diaphragm muscle weakness is a correlate of persistent dyspnea despite normal lung/cardiac function one year after hospitalization for COVID-19. Objectives: To determine the persistence and pathophysiological nature of diaphragm muscle weakness and its association with exertional dyspnea at 2 years after hospitalization for COVID-19, and investigate the impact of inspiratory muscle training (IMT) on diaphragm muscle weakness and exertional dyspnea in individuals with long COVID. Methods: ~2 years after hospitalization for COVID-19, 30 individuals (11 female, age 61±14 years) underwent comprehensive respiratory muscle assessment and evaluation of dyspnea. Eighteen with persistent diaphragm muscle weakness and exertional dyspnea were randomized to undergo six weeks of IMT or sham training; assessments were repeated immediately after and 6 weeks after IMT completion. Results: Moderate-severe exertional dyspnea with related diaphragm muscle weakness persisted 28 months after hospital discharge with every third patient reporting no, moderate or severe dyspnea, respectively. Diaphragm muscle weakness on exertion and reduced diaphragm cortical activation were related to exertional dyspnea. IMT improved diaphragm muscle function, diaphragm fatiguability (time to task failure 472±247 vs. 1219±979 sec; p=0.05), diaphragm voluntary activation index and dyspnea (Borg score 6.89±1.83 vs. 5.67±1.50; p=0.03); improvements persisted at 6 weeks after the end of IMT. Conclusions: This study is the first to identify a treatment for persisting dyspnea in long COVID, and provide a pathophysiological explanation for the treatment benefit.