What does this study add to the field?Using latent class analysis (LCA), we identified two subgroups among a cohort of 483 patients with COVID-19-related ARDS. Class 2 patients had higher inflammatory markers and lactate and corresponded with the previously identified hyperinflammatory subphenotype, whereas Class 1 corresponded with the hypoinflammatory subphenotype. Class 2 had significantly higher 90-day mortality compared with Class 1 (75% vs 48%; p<0•0001). Differential response to corticosteroid treatment was observed, with decreased mortality in steroid-treated patients in Class 2 but not Class 1. SARS-CoV-2 polymerase chain reaction cycle threshold was a predictor of mortality in Class 1, but not Class 2, suggesting distinct drivers of mortality among classes.

Frontline health-care workers experienced moral injury long before COVID-19, but the pandemic highlighted how pervasive and damaging this psychological harm can be. Moral injury occurs when individuals violate or witness violations of deeply held values and beliefs. We argue that a continuum exists between moral distress, moral injury, and burnout. Distinguishing these experiences highlights opportunities for intervention and moral repair, and may thwart progression to burnout.

During a consensus conference in Lugano, Switzerland, 175 statements on controlled clinical trials were drafted by 47 representatives from academia, governmental registration agencies and industry in nine countries. Their opinion on these statements was similar to that of 47 'matched pairs' who did not attend the conference. Thus, the opinion of participants and non-participants appears to reflect the general opinion of those currently involved in designing, conducting and analysing controlled clinical trials. The Lugano statements give answers to the following questions: Is the controlled clinical trial in a crisis? What is the motivation to perform controlled clinical trials? Is it possible for a physician participating in a controlled clinical trial to act in the patient's best interest? Is it possible to obtain truly informed consent in a controlled clinical trial? When is it ethical to withhold active treatment in a controlled clinical trial? What are the controversial issues in the design of a good controlled clinical trial? Is there a double standard with respect to efficacy and adverse drug reactions in controlled clinical trials? What are the alternatives to controlled clinical trials and when should they be performed? How can sponsor bias be minimized? How should an ethics committee decide whether a controlled clinical trial is ethical? Should registration agencies become directly involved in the planning and conduct of controlled clinical trials? Do the declarations of Tokyo and Helsinki facilitate the conduct of ethically valid controlled clinical trials? Is it possible to create an international standard for the conduct and regulation of controlled clinical trials? Why do messages from controlled clinical trials filter into medicine so slowly? Is it possible to bridge the gap between controlled clinical trials and clinical reality? What are the costs of doing and not doing controlled clinical trials? When should drug companies decide to start a trial programme with a specific compound? Is there public hostility against controlled clinical trials? If so, how can it be reduced? The respondents almost unanimously felt that controlled clinical trials are a must: the public must be told that progress in medicine depends on controlled clinical trials, that patients often benefit from participating in them and that the alternative, practising in the face of constant uncertainty, is worse than the possible disadvantages related to the conduct of the trial.