Survivors of critical illness experience significant skeletal muscle weakness and physical disability, which can persist for at least 5 years.^1,2 Muscle wasting contributes substantially to weakness acquired in the intensive care unit (ICU),^1,3 but its time course and underlying pathophysiological mechanisms remain poorly characterized and understood. In health, muscle mass is maintained through balanced protein breakdown and synthesis.⁴ For wasting to occur, breakdown must be increased relative to synthesis.

The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. UK Research and Innovation and National Institute for Health Research.

Quiz Ref ID Chronic obstructive pulmonary disease (COPD) is characterized by recurrent exacerbations that can cause intermittent periods of severe clinical deterioration requiring hospitalization and ventilator support. Although treating patients with COPD and acute respiratory failure with noninvasive ventilation improves outcomes,^1,2 persistent hypercapnia after an exacerbation is associated with excess mortality^3,4 and early rehospitalization.⁵ In 2013, the 28-day COPD readmission rate was around 20%,⁶ and there were financial penalties in place in the United Kingdom and United States for such early readmissions. These data have contributed to readmission prevention being a priority area for clinicians.

Rationale: Profound muscle weakness during and after critical illness is termed intensive care unit–acquired weakness (ICUAW). Objectives: To develop diagnostic recommendations for ICUAW. Methods: A multidisciplinary expert committee generated diagnostic questions. A systematic review was performed, and recommendations were developed using the Grading, Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Measurement and Main Results: Severe sepsis, difficult ventilator liberation, and prolonged mechanical ventilation are associated with ICUAW. Physical rehabilitation improves outcomes in heterogeneous populations of ICU patients. Because it may not be feasible to provide universal physical rehabilitation, an alternative approach is to identify patients most likely to benefit. Patients with ICUAW may be such a group. Our review identified only one case series of patients with ICUAW who received physical therapy. When compared with a case series of patients with ICUAW who did not receive structured physical therapy, evidence suggested those who receive physical rehabilitation were more frequently discharged home rather than to a rehabilitative facility, although confidence intervals included no difference. Other interventions show promise, but fewer data proving patient benefit existed, thus precluding specific comment. Additionally, prior comorbidity was insufficiently defined to determine its influence on outcome, treatment response, or patient preferences for diagnostic efforts. We recommend controlled clinical trials in patients with ICUAW that compare physical rehabilitation with usual care and further research in understanding risk and patient preferences. Conclusions: Research that identifies treatments that benefit patients with ICUAW is necessary to determine whether the benefits of diagnostic testing for ICUAW outweigh its burdens.

Acute hypoxemic respiratory failure is a key clinical characteristic of COVID-19 pneumonitis. In a study of 63 792 patients with COVID-19 hospitalized in the UK between March and August 2020, 76% required supplemental oxygen and 9% required tracheal intubation and invasive mechanical ventilation.¹ Early in the pandemic, international experiences highlighted the potential risk that intensive care units (ICUs) might become overwhelmed, and high mortality was observed in patients requiring invasive mechanical ventilation.^2-4 This drove an urgent public health need to identify strategies to reduce the demand for invasive mechanical ventilation.