After mild COVID-19, a subgroup of patients reported post–acute-phase sequelae of COVID-19 (PASC) in which exertional dyspnea and perceived exercise intolerance were common. Underlying pathophysiological mechanisms remain incompletely understood. The purpose of this study was to examine outcomes from cardiopulmonary exercise testing (CPET) in these patients. In this observational study, participants were patients who were referred for the analysis of PASC after mild COVID-19 and in whom CPET was performed after standard clinical workup turned out unremarkable. Cardiocirculatory, ventilatory, and metabolic responses to and breathing patterns during exercise at physiological limits were analyzed. Twenty-one patients (76% women; mean age = 40 years) who reported severe disability in physical functioning underwent CPET at 32 weeks (interquartile range = 22–52) after COVID-19. Mean peak O₂ uptake was 99% of predicted with normal anaerobic thresholds. No cardiovascular or gas exchange abnormalities were detected. Twenty of the 21 patients (95%) demonstrated breathing dysregulation (ventilatory inefficiency [29%], abnormal course of breathing frequency and tidal volume [57%], absent increase of end-tidal Pco₂ [57%], and abnormal resting blood gases [67%]). Breathing dysregulation may explain exertional dyspnea and perceived exercise intolerance in patients with PASC after mild COVID-19 and can be present in the absence of deconditioning. This finding warrants further study on the levels of neural control of breathing and muscle function, and simultaneously provides a potential treatment opportunity. This study contributes to the understanding of persistent exertional dyspnea and perceived exercise intolerance following mild COVID-19, which is vital for the development of effective rehabilitation strategies.

Muscle weakness is a prominent symptom in post-acute sequelae of COVID-19 (PASC). However, few studies have objectively and longitudinally assessed muscle strength after varying COVID-19 severity grades. This observational study aimed to explore the prevalence, determinants, and 1.5 years change of quadriceps muscle weakness in 98 patients discharged from COVID-19 hospitalization and in 50 patients with PASC following mild COVID-19. Isometric quadriceps maximal voluntary contraction (MVC) was assessed on a computerized dynamometer at three visits. Also, in a subgroup of 14 post-COVID-19 patients with quadriceps muscle weakness, muscle thickness and echo intensity were determined by muscle ultrasound of nine upper and lower extremity muscles. Muscle weakness was found in 59% of post-hospitalized patients and in 65% of those with PASC following mild COVID-19 at ~14 weeks after acute COVID-19. Whereas during ~1.5 years follow-up MVC modestly improved, muscle weakness prevalence remained unchanged. Hospital length of stay and diabetes mellitus were identified as possible predictors of muscle weakness following COVID-19 hospitalization. No predictors could be identified in those with PASC following mild COVID-19. Ultrasound outcomes revealed no large structural abnormalities. In conclusion, clinically relevant muscle weakness is common after COVID-19 and its long-term improvement is poor. Future studies with relevant control groups are warranted to confirm our data.

After Covid-19, up to 10% experience post-acute sequelae of Covid-19 (PASC). We provide observational follow-up data on perceived health change, symptoms, lung function, muscle strength, and labor participation up to 10 months after infection. Methods: We included 168 SARS-CoV-2 infected patients who visited the Radboud University Medical Center Covid-19 multidisciplinary clinic twice. 108 were previously hospitalized for Covid-19, while 60 were referred from primary care for persisting symptoms. Health change (SF-36), fatigue (CIS-Fatigue), dyspnea (mMRC), pain (VAS), anxiety and depression (HADS), cognitive complaints (CFQ) and labor participation were assessed. Also, lung function and quadriceps strength were measured. Results: Hospitalized post-Covid-19 patients improved on perceived health change, fatigue, dyspnea, lung diffusion capacity, muscle strength and labor participation (all p<0.05). However, abnormal fatigue, muscle strength, lung diffusion capacity, dyspnea, and cognitive functioning, were still observed in 60, 49, 31, 21, and 21% after 7 months, respectively. Referred patients improved significantly on perceived health change, fatigue, dyspnea, anxiety and muscle strength (all p<0.05). However, abnormal fatigue, muscle strength, health status, cognitive functioning, dyspnea, depression, and pain were still observed in 69, 55, 47, 28, 24, 23, and 22% after 10months, respectively. At second visit, 41% of hospitalized and 56% of referred patients had not fully returned to work. Conclusion: PASC is now emerging as a next global health and economic problem given the scale, the physical and psychological burden with seemingly slow recovery and associated long-term loss of productivity.