In two of 12 patients with clinical glucocorticoid resistance, mutant forms of GR could be found. The glucocorticoid resistance in vivo in these two patients corresponds to impaired function of the two mutated GR forms in two in vitro assays. The relevance of the conservative polymorphism for the glucocorticoid insensitivity noted in these patients remains to be clarified.

The impaired DNA-binding of the hGR, R477H mutant may explain the severe phenotype of cortisol resistance seen with this mutation. The dominant negative effects of both mutants on wild-type GR signalling probably contribute to the patients' cortisol resistance.

IntroductionThe COVID-19 pandemic has had a profound effect on many domains of healthcare. Even in high-income countries such as Sweden, the number of patients has vastly outnumbered the resources in affected areas, in particular during the first wave. Staff caring for patients with COVID-19 in intensive care units (ICUs) faced a very challenging situation that continued for months. This study aimed to describe burnout, safety climate and causes of stress among staff working in COVID-19 ICUs.MethodA survey was distributed to all staff working in ICUs treating patients with COVID-19 in five Swedish hospitals during 2020 and 2021. The numbers of respondents were 104 and 603, respectively. Prepandemic data including 172 respondents from 2018 served as baseline.ResultsStaff exhaustion increased during the pandemic, but disengagement decreased compared with prepandemic levels (p<0.001). Background factors such as profession and work experience had no significant impact, but women scored higher in exhaustion. Total workload and working during both the first and second waves correlated positively to exhaustion, as did being regular ICU staff compared with temporary staff. Teamwork and safety climate remained unchanged compared with prepandemic levels.Respondents reported ‘making a mistake’ as the most stressful of the predefined stressors. Qualitative analysis of open-ended questions identified ‘lack of knowledge and large responsibility’, ‘workload and work environment’, ‘uncertainty’, ‘ethical stress’ and ‘organization and teamwork’ as major causes of stress.ConclusionDespite large workloads, disengagement at work was low in our sample, even compared with prepandemic levels. High levels of exhaustion were reported by the ICU staff who carried the largest workload. Multiple significant causes of stress were identified, with fear of making a mistake the most significant stressor.