Lower diaphragmatic thickness found among long COVID patients with unspecific fatigue and dyspnea

In a recent study posted to the medRxiv* preprint server, researchers defined the sonographic diaphragm phenotype of long coronavirus disease (COVID) patients with unspecific fatigue and dyspnea.

The authors of the present study previously reported on neuromuscular pathophysiological changes underlying chronic functional impairments among severe COVID 2019 (COVID-19) patients requiring inpatient rehabilitation for recovery. However, the extent of neuromuscular involvement among patients with lesser COVID-19 needs further research, and ultrasonographic findings among long COVID patients in outpatient rehabilitation settings are yet to be reported.

About the study

In the present retrospective cohort study, researchers extended their previous analysis and investigated if dysfunction of the diaphragm muscle contributed to persistent long COVID symptoms such as dyspnea and/or fatigue.

The study cohort comprised 37 polymerase chain reaction (PCR)-confirmed (81%) or clinically diagnosed long COVID patients referred for ultrasonic neuromuscular assessment from a pulmonary medicine clinic without a clearly defined cardiopulmonary etiology for their symptoms. Out of the study cohort, 27 were never hospitalized due to COVID-19 and none of the patients required mechanical ventilation.

The study participants were enrolled for the study between 25 February 2021 and 7 October 2021. For comparison, published datasets of healthy individuals (n=150) and a prior dataset of severe COVID-19 patients requiring inpatient rehabilitation (n = 21) were used. The B-mode ultrasound of the diaphragm was performed for the participants, in which diaphragmatic thickness was assessed based on the total lung capacity (TLC) and functional reserve capacity (FRC).

In addition, the team reported functional outcomes among patients who completed an outpatient cardiopulmonary physical therapy program which included cardiovascular conditioning, with continual monitoring of heart rate, oxygen saturation (SpO2), and perceived exertion rate. To determine the impact of systemic inflammation markers on muscle wasting, the serum creatine kinase (CK), C-reactive protein (CRP), creatinine, D-Dimer, albumin, bicarbonate, and neutrophil to lymphocyte ratio were assessed.

Before the ultrasound referral, the medical history of all patients was obtained and the participants underwent a physical examination. Patients received respiratory muscle training with a home exercise based on resistance during the periods of inspiration and expiration to be completed five times per day. Additionally, the participants were educated on the strategies for diaphragmatic, shortness of breath, and cardiovascular conditioning habit-forming strategies.

In addition, 70% (n=26) patients underwent computed tomography (CT) radiographic examination, pulmonary function tests were obtained in 31 patients (84%), and 81% patients (n=30) underwent six-minute walk tests. Over 88% of patients (n=33) underwent electrodiagnostic tests which included phrenic nerve conduction analysis and limited needle electromyography examination of the vastus lateralis and/or biceps brachii muscle.

Results

Sonographic pathological abnormalities were detected among 65% of patients (n=24), of which most of the patients (n=23) demonstrated low hemi-diaphragmatic thickness (<0.15 cm) at FRC and thinner diaphragm musculature correlated positively with lower serological CK and creatinine values. However, no association was observed with systemic inflammatory markers.

The authors speculated that the findings represented a type of disuse atrophy, a condition responsive to cardiopulmonary physical therapy. In accordance, among the patients, 78% (14 out of 18) who underwent outpatient cardiopulmonary therapy and 75% (n=6) patients who took the six-minute walk tests showed functional improvements.

The average values for both the left and right hemi-diaphragmatic thickness were 0.17 ± 0.07 cm with average corresponding thickness ratios for the left and right hemi-diaphragms of 2.0 ± 0.4 cm and 2.0 ± 0.5 cm, respectively. Compared to the reference population requiring inpatient rehabilitation, the study participants (requiring outpatient rehabilitation) exhibited substantially lesser thickness and higher diaphragmatic thickening ratios for the right and left hemi-diaphragms.

In the study cohort, the medians for FVC, TLC, and the forced expiratory volume in one second (FEV1) were 89%, 95.5%, and 91%, respectively. The medians for FEV1/FVC ratio and the diffusing capacity for carbon monoxide (DLCO) were 79% and 84%, respectively.

The most common CT abnormalities among the patients were pulmonary nodules (most of which were sized <5.5mm) and opacities (band-like or ground glass-like) denoting fibrosis. In the electromyography analysis, no abnormalities were observed among the patients, indicative of unaltered muscle contractility in the study cohort and none of the participants were diagnosed with phrenic neuropathies.

Overall, the study findings showed that the diaphragm muscle thickness is lower among long COVID patients with lower COVID-19 severity (and unspecific dyspnea and fatigue) who require outpatient rehabilitation compared to those with less severe COVID-19 and inpatient rehabilitation requirements.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.