WHIPLASH: The possible impact of context on diagnosis

This study explores the importance of context when diagnosing Whiplash Associated Disorders (WAD). Whiplash is a complex injury and there is considerable variation in its diagnosis and treatment. Research has focussed on RTAs, whilst there is a paucity of evidence relating to WAD in sport. It is unclear whether WAD is simply not occurring in sport, or if such injuries are occurring but are not identified as WAD. In the current study, 87 postgraduate physiotherapists were asked to classify an injury reported in a short vignette. Two parallel vignettes were used, which were identical except for the context of the injury (one being an RTA and the other being within sport). Each participant responded to only one of these. It was found that, even within a sample of experienced physiotherapists, the injury environment impacted on diagnosis, despite the symptoms being identical. A significantly higher proportion of therapists diagnosed WAD within the RTA context than within the sporting context. Additionally, there were differences between the two context groups in relation to the diagnostic terminology used by participants. Most respondents had heard of the CSP whiplash guidelines but only a minority had actively used these. The majority of respondents were also aware of the litigation aspects of RTAs

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease