• Jens Spiesshoefer, Binaya Regmi, Mehdi Senol, Benedikt Jörn, Oscar Gorol, Mustafa Elfeturi, Stephan Walterspacher, Alberto Giannoni, Florian Kahles, Rainer Gloeckl, and Michael Dreher.
• University Hospital Aachen, 39058, Pneumology and Intensive Care Medicine Division, Aachen, Nordrhein-Westfalen, Germany; jspiesshoefer@ukaachen.de.
• Am. J. Respir. Crit. Care Med. 2024 May 19.

RationaleDiaphragm muscle weakness might underly persistent exertional dyspnea despite normal lung/cardiac function in individuals previously hospitalized for acute COVID-19 illness.ObjectivesFirstly, to determine the persistence and pathophysiological nature of diaphragm muscle weakness and its association with exertional dyspnea two years after hospitalization for COVID-19, and secondly to investigate the impact of inspiratory muscle training (IMT) on diaphragm and inspiratory muscle weakness and exertional dyspnea in individuals with long COVID.Methods~2 years after hospitalization for COVID-19, 30 individuals (11 female, median age 58 [interquartile range (IQR) 51-63] years) underwent comprehensive (invasive) respiratory muscle assessment and evaluation of dyspnea. Eighteen with persistent diaphragm muscle weakness and exertional dyspnea were randomized to 6 weeks of IMT or sham training; assessments were repeated immediately after and 6 weeks after IMT completion. The primary endpoint was change in inspiratory muscle fatiguability immediately after IMT.ResultsAt median 31 [IQR 23-32] months after hospitalization, 21/30 individuals reported relevant persistent exertional dyspnea. Diaphragm muscle weakness on exertion and reduced diaphragm cortical activation were potentially related to exertional dyspnea. Compared with sham control, IMT improved diaphragm and inspiratory muscle function (sniff transdiaphragmatic pressure 83 [IQR 75-91] vs. 100 [IQR 81-113] cmH2O; p=0.02), inspiratory muscle fatiguability (time to task failure 365 [IQR 284-701] vs. 983 [IQR 551-1494] sec; p=0.05), diaphragm voluntary activation index (79 [IQR 63-92] vs 89 [IQR 75-94]%; p=0.03), and dyspnea (Borg score 7 [IQR 5.5-8] vs. 6 [IQR 4-7]; p=0.03); improvements persisted for 6 weeks after IMT completion.ConclusionsThis study is the first to identify a potential treatment for persisting exertional dyspnea in long COVID, and provide a possible pathophysiological explanation for the treatment benefit. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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