Persisting exertional dyspnea and perceived exercise intolerance after mild Covid-19: a critical role for breathing dysregulation?

Background: After mild Covid-19, a subgroup of patients reports post-acute sequelae of Covid-19 (PASC), in which exertional dyspnea and perceived exercise intolerance are common. Underlying pathophysiological mechanisms remain incompletely understood. We studied outcomes from cardiopulmonary exercise test (CPET) in these patients. Method(s): In this observational study, we included patients referred for the analysis of PASC after mild Covid-19 in whom CPET was performed after standard clinical work-up turned out unremarkable. Cardiocirculatory, ventilatory and metabolic response to, and breathing patterns during exercise at physiological limits were analyzed. Result(s): Twenty-one patients (76% female, mean age 40y) who reported severe fatigue (CIS-fatigue >= 35), dyspnea (mMRC 2 (IQR1-2)) and disability in physical role functioning (SF-36) underwent CPET at 32 weeks (IQR 22-52) after Covid-19. Mean peak oxygen uptake was 99% (SD13) of predicted with normal anaerobic thresholds at 62% (SD11) of predicted oxygen uptake. No cardiovascular or gas exchange abnormalities were detected. Twenty out of the 21 patients (95%) demonstrated breathing dysregulation, existing of ventilatory inefficiency (29%), abnormal course of breathing frequency and tidal volume (57%), and acute or chronic respiratory alkalosis in resting blood gases (67%). Conclusion(s): In the absence of deconditioning, breathing dysregulation may explain the experienced exertional dyspnea and exercise intolerance in patients with PASC after mild Covid-19.

Post-acute prevalence of occult pulmonary embolism after hospitalisation for Covid-19

Background: During hospitalization for Covid-19 the prevalence of pulmonary embolism (PE) is ~15%. Occult PE may be undiagnosed during hospitalization. Also, after discharge, factors such as residual (local) inflammation and relative physical inactivity may predispose to PE. Aim(s): To study the presence of occult PE and pulmonary perfusion defects three months after discharge from hospitalization for Covid-19. Method(s): In this prospective study we performed CT pulmonary angiography (CTPA) in adults three months after discharge from hospitalization for moderate-to-critical Covid-19. Exclusion criteria: therapeutic anticoagulation, diagnosed PE during hospitalization, CTPA contra-indications. Primary outcome measure was presence of PE. Secondary outcomes were wedge shaped perfusion defects on subtraction iodine maps, D-dimer concentration, presence of Years criteria at follow-up, and pulmonary parenchymal abnormalities. Result(s): 26 patients (65% male, 61 (SD10) y, hospital length of stay 11 (IQR9-15) days, 34% ICU treatment) underwent CTPA at 13 (SD2) weeks after discharge. 25 patients (96%) had no evidence for PE while one post-ICU patient demonstrated a suspected partial occlusion of a subsegmental pulmonary artery. No wedge shaped perfusion defects were found. D-Dimer values were <1000 ng/ml in all patients and none had Years criteria. Extent of parenchymal abnormalities decreased compared to acute phase (CT severity score 7 (SD5) vs 13 (SD5), p=0.004). Conclusion(s): Prevalence of occult PE three months after discharge from hospitalization for Covid-19 was negligible in our sample. CTPA should not be routinely performed in these patients. .

Post-Covid-19 peripheral muscle weakness is not associated with muscle ultrasound echogenicity or muscle thickness

Background: Peripheral muscle weakness has been observed in the post-acute phase of Covid-19 patients. However, it is unknown whether Covid-19 is associated with structural changes in skeletal muscles, like atrophy, inflammation or fibrosis. Aim(s): To examine whether peripheral muscle weakness in post-Covid-19 patients is associated with changes in muscle echogenicity and thickness. Method(s): Post-Covid-19 patients with objectified muscle weakness (isometric quadriceps maximal voluntary contraction (MVC) <lower limit of normal) at ~6 months after infection were cross-sectionally studied. Vastus lateralis (VL), rectus femoris (RF), tibialis anterior (TA) and gastrocnemius (GCM) were examined unilaterally using quantitative muscle ultrasound. Standardized scores (z-scores) of 2 were defined as limits of normal. Result(s): Fourteen post-Covid-19 patients were included (age 47+/-15y, 64% male, BMI 26+/-3 kg/m2). Median z-scores were determined for muscle thickness and echogenicity of VL (-1.0 [-1.3- -0.2], 0 [-0.2-1.1]), RF (-0.2 [-1.4-0.1], -0.2 [-1.3-0.6]), TA (0.1 [-0.8-0.6], 0.5 [-0.4-1.0]), and GCM (0.8 [0.1-1.0], -0.7 [-1.3- -0.1]), respectively. Thirteen patients had values within the limits of normal. One patient showed increased echogenicity of VL, but normal values for other muscles. There were significant moderate-to-strong correlations between MVC and muscle thickness of VL (r=0.670), RF (r=0.812), TA (r=0.593) and GCM (r=0.579), and between MVC and echogenicity of GCM (r=-0.588). Conclusion(s): In a cohort of post-Covid-19 patients with peripheral muscle weakness, standardized muscle ultrasound investigations did not show any evidence for structural abnormalities.

1,5-year course of quadriceps muscle strength following mild-to-critical Covid-19

Background: Muscle weakness is prevalent among post-Covid-19 patients, but longitudinal studies quantifying muscle strength following Covid-19 are lacking. Aim(s): To describe the course of quadriceps muscle strength over ~1,5 year following Covid-19. Method(s): A prospective analysis of 63 hospitalized (age 60+/-9y, 68% male) and 31 non-hospitalized (age 52+/-15y, 36% male) post-Covid-19 patients with persisting symptoms ('long covid') was performed. Isometric quadriceps maximal voluntary contraction (MVC) was evaluated using a computerized dynamometer at a knee angle of 60degree during 3 visits in hospitalized (89 [80-104], 215 [198-233], 434 [416-478] days after Covid-19) and non-hospitalized (138 [114-176], 282 [249-347], 540 [486-596] days after Covid-19) patients. MVC was expressed as percentage predicted and muscle weakness was defined as MVC <lower limits of normal. Result(s): Over the 3 visits, hospitalized patients had a MVC of 65+/-18, 70+/-17, and 68+/-16 %pred, and muscle weakness was present in 54, 49, 51% of cases, respectively. Similarly, non-hospitalized patients had a MVC of 70+/-16, 76+/-17, and 74+/-19 %pred, and a muscle weakness prevalence of 65, 52, and 52% was found. In both groups, MVC improved between visit 1 and 2 (p<0,05) whereas no change was observed between visit 2 and 3. The prevalence of muscle weakness in both groups did not change significantly. Conclusion(s): Quadriceps muscle strength modestly improves during the first 7-9 months following acute Covid-19 in both hospitalized and non-hospitalized 'long covid' patients. However, still half of the patients in both groups had long-term muscle weakness. Further investigation is needed into the aetiology of muscle weakness in post-Covid-19 patients.

Comparison between myocardial function assessed by echocardiography during hospitalization for COVID-19 and at 4 months follow-up.

In patients hospitalized for corona virus infectious disease 19 (COVID-19) it is currently unknown whether myocardial function changes after recovery and whether this is related to elevated cardiac biomarkers. In this single center, prospective cohort study we consecutively enrolled hospitalized COVID-19 patients between 1 April and 12 May 2020. All patients underwent transthoracic echocardiography (TTE) evaluation during hospitalization and at a median of 131 days (IQR; 116-136) follow-up. Of the 51 patients included at baseline, 40 (age: 62 years (IQR; 54-68), 78% male) were available for follow-up TTE. At baseline, 68% of the patients had a normal TTE, regarding left ventricular (LV) and right ventricular (RV) volumes and function, compared to 83% at follow-up (p = 0.07). Median LV ejection fraction (60% vs. 58%, p = 0.54) and tricuspid annular plane systolic excursion (23 vs 22 mm, p = 0.18) were comparable between hospitalization and follow-up, but a significantly lower RV diameter (39 vs. 34 mm, p = 0.002) and trend towards better global longitudinal strain (GLS) (- 18.5% vs - 19.1%, p = 0.07) was found at follow-up. Subgroup analysis showed no relation between patients with and without elevated TroponinT and/or NT-proBNP during hospitalization and myocardial function at follow-up. Although there were no significant differences in individual myocardial function parameters at 4 months follow-up compared to hospitalisation for COVID-19, there was an overall trend towards normalization in myocardial function, predominantly due to a higher rate of normal GLS at follow-up.

[Post-COVID-19 rehabilitation;a matter of customisation]

In the early phase of the COVID-19 pandemic, knowledge about the natural course of recovery of COVID-19 is limited. We therefore describe - based on generic knowledge of post IC syndrome (PICS) and (pulmonary) rehabilitation - the possibilities to organize personalized rehabilitation programs in several care settings. To illustrate variety in need for rehabilitation, we described three cases of critical COVID-19 disease survivors after treatment in the intensive care unit. Some patients require immediate rehabilitation following hospitalization, but rehabilitation may also be initiated in the home environment. For the latter population monitoring of progress and recovery should be organized to assess whether a more intensified multidisciplinary rehabilitation program is needed. This may be initiated in one of the medical rehabilitation centers or in pulmonary rehabilitation centers. Post-COVID-19 rehabilitation, regardless of the specific form, should be patient-centered and multidisciplinary organized.