Cardiopulmonary work up of patients with and without fatigue 6 months after COVID-19 (preprint)

The pathogenesis of post-COVID-19 symptoms remains incompletely understood. Therefore, we aimed to determine cardiopulmonary limitations six months after surviving COVID-19 using pulmonary function tests (PFTs), echocardiographic studies to the point of analyses of global-longitudinal-strain (GLS), which describes the cycling myocardium deformation and provides better data on left ventricular (LV) dysfunction than LV ejection fraction (LVEF), and validated questionnaires. Overall, 60 consecutive hospitalized patients were included (61±2 years, 32% treated in the ICU). At follow-up (194±3 days after discharge), fatigue was the most prevalent symptom (28%). Patients with fatigue were more symptomatic overall and characterized by worse quality of life (QoL) scores compared to patients without fatigue (all p<0.05), mainly due to limited mobility and high symptom burden. While PFT variables and LVEF were normal in the vast majority (LVEF=52% (45%-52%)) of patients, GLS was significantly reduced (-15%(-18%_-14%)). However, GLS values were not different between patients with and without fatigue. In conclusion, fatigue was the most prevalent post-COVID-19 symptom in our cohort, which was associated with worse QoL mainly due to limited mobility and the high burden of concomitant symptoms. Patients showed a subtle myocardial dysfunction six months after surviving COVID-19, but this did not relate to the presence of fatigue.

Diaphragm Dysfunction as a Determinant of Persisting Dyspnoea in Patients One Year after Invasive Mechanical Ventilation Due to COVID-19 Related ARDS (preprint)

Background: Some patients with coronavirus disease 2019 (COVID-19) experience prolonged fatigue and dyspnoea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a possible pathophysiological correlate after severe COVID-19 acute respiratory distress syndrome (ARDS).Methods:Ten patients with severe COVID-19 ARDS treated with invasive mechanical ventilation (IMV) (6 female, age 56±14 years, 63±45 days of IMV) and ten matched healthy controls underwent pulmonary function tests (PFTs), 6-minute walk test, echocardiography, diaphragm ultrasound, and invasive recording of twitch transdiaphragmatic pressure (twPdi) following magnetic diaphragm stimulation. Twitch interpolation was used to determine the diaphragm voluntary activation index (DVAI); reflecting central diaphragm activation.Findings: One year post discharge, neither PFTs nor echocardiography were indicative of significant abnormalities in severe COVID-19 survivors. However, six patients reported persisting dyspnoea on exertion (severe in two, moderate in four). On ultrasound, the diaphragm thickening ratio was lower in patients versus controls (1.87±0.37 vs. 2.76±0.72; p<0.01), and diaphragm excursion velocity during a maximum sniff manoeuvre was associated with dyspnoea. TwPdi following cervical magnetic stimulation did not differ between patients and controls overall, but twPdi half relaxation time progressively increased in parallel with dyspnoea severity (ANOVA p=0.03), while sniff Pdi progressively decreased (ANOVA p=0.05). DVAI was lower in patients versus controls (30±27% vs 79±6%, p<0.01) and was associated with dyspnoea (ANOVA p=0.05).Interpretation: Inspiratory muscle dysfunction with impaired central voluntary activation of the diaphragm is present one year after severe COVID-19 ARDS treated with IMV, and relates to dyspnoea.Trial Registration: This prospective case-control study was registered with number, (NCT04854863)Funding: None to declare. Declaration of Interest: The authors have no conflicts of interest to disclose.Ethical Approval: This study was approved by the local ethics committee (Ethikkommission an der Medizinischen Fakultät der Rheinisch-Westfälischen Technischen Hochschule Aachen, CTCA-A-Nr. 20-515, AZ EK 443/20).