ABSTRACT
The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus ('Long COVID') is not fully understood. Cases were recruited from a Long COVID clinic (N=32; 44{+/-} 12y; 10(31%)men), and age/sex-matched healthy controls (HC) (N=19; 40{+/-} 13y; 6(32%)men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means(95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced Oxygen Uptake Efficiency Slope (1847(1679,2016) vs (2176(1978,2373) ml/min, p=0.002) and Anaerobic Threshold (13.2(12.2,14.3) vs 15.6(14.4,17.2) ml/Kg/min, p<0.001), and lower oxidative capacity on near infrared spectroscopy ({tau}: 38.7(31.9,45.6) vs 24.6(19.1,30.1) seconds, p=0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multi-system factors might contribute to impaired exercise tolerance in Long COVID sufferers.
Subject(s)
Fatigue , Disruptive, Impulse Control, and Conduct DisordersABSTRACT
Background. Complications following SARS-CoV-2 infection require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated Post-COVID clinical service to include both hospitalised and non-hospitalised patients. Methods. In a single-centre, observational analysis, we report outcomes for 1325 individuals assessed in the University College London Hospitals NHS Foundation Trust Post-COVID service between April 2020 and April 2021. Demography, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation were compared by referral route ('post hospitalisation', PH; 'non-hospitalised', NH; and 'post emergency department', PED). Symptoms associated with poor recovery or inability to return to work full-time were assessed using multivariable logistic regression. Findings. 1325 individuals were assessed (PH 547 [41.3%], PED 212 [16%], NH 566 [42.7%]. Compared with PH and PED groups, NH were younger (median 44.6 [35.6-52.8] vs 58.3 [47.0-67.7] and 48.5 [39.4-55.7] years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be from an ethnic minority (30.9%, 52.7% and 41.0%) and seen later after symptom onset (median [IQR]:194 [118-298], 69 [51-111] and 76 [55-128] days) (all p<0.0001). NH patients had similar rates of onward specialist referral as PH and PED groups (18.7%, 16.1% and 18.9%, p=0.452), and were more likely to require support for breathlessness (23.7%, 5.5% and 15.1%, p<0.001) and fatigue (17.8%, 4.8%, 8.0%, p<0.001). Hospitalised patients had higher rates of pulmonary emboli, persistent lung interstitial abnormalities, and other organ impairment. 716 (54.0%) individuals reported <75% of optimal health (median [IQR] 70% [55%-85%]). Overall, less than half of employed individuals felt able to return to work full-time at first assessment. Interpretation. Symptoms following SARS-CoV-2 infection were significant in both post- and non-hospitalised patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.
Subject(s)
COVID-19ABSTRACT
Background A diagnosis of MND takes an average 10-16 months from symptom onset. Early diagnosis is important to access supportive measures to maximise quality of life. The COVID-19 pandemic has caused significant delays in NHS pathways; the majority of GP appointments now occur online with subsequent delays in secondary care assessment. Given the rapid progression of MND, patients may be disproportionately affected resulting in late stage new presentations. We used Monte Carlo simulation to model the pre-COVID-19 diagnostic pathway and then introduced plausible COVID-19 delays. Methods The diagnostic pathway was modelled using gamma distributions of time taken: 1) from symptom onset to GP presentation, 2) for specialist referral, and 3) for diagnosis reached after neurology appointment. We incorporated branches to simulate delays: when patients did not attend their GP and when the GP consultation did not result in referral. An emergency presentation was triggered when diagnostic pathway time was within 30 days of projected median survival. Total time-to-diagnosis was calculated over 100,000 iterations. The pre-COVID-19 model was estimated using published data and the Improving MND Care Survey 2019. We estimated COVID-19 delays using published statistics. Results The pre-COVID model reproduced known features of the MND diagnostic pathway, with a median time to diagnosis of 399 days and predicting 5.2% of MND patients present as undiagnosed emergencies. COVID-19 resulted in diagnostic delays from 558 days when only primary care was 25% delayed, to 915 days when both primary and secondary care were 75%. The model predicted an increase in emergency presentations ranging from 15.4%-44.5%. Interpretations The model suggests the COVID-19 pandemic will result in later-stage diagnoses and more emergency presentations of undiagnosed MND. Late-stage presentations may require rapid escalation to multidisciplinary care. Proactive recognition of acute and late-stage disease with altered service provision will optimise care for people with MND. Funding - This research was supported and funded by a grant from the Reta Lila Weston Trust. NS was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.