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.

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Previously, it has been shown that following muscle unloading, males and females experience different maladaptations in neuromuscular function. As a follow-up, the present investigation sought to determine if male and female neuromuscular systems demonstrated similar, or disparate morphological adaptations to muscle unloading. Twenty young adult male, and 20 young adult female rats were randomly assigned to one of two treatment protocols: muscle unloading, or control conditions. Following the 2 week intervention period, immunofluorescent procedures were used to quantify pre- and post-synaptic features of neuromuscular junctions (NMJs), and to assess myofiber profiles (size and fiber type composition) of the soleus, plantaris, and EDL muscles. A 2-way ANOVA with main effects for sex and treatment was then used to identify statistically significant (P ≤ 0.05) differences among structural parameters. Analysis of NMJs showed a consistent lack of differences between males and females. Overall, NMJs were also found to be resistant to the effects of unloading. When examining myofiber profiles, however, male myofibers were revealed to be significantly larger than female ones in each of the muscles examined. Unloading resulted in significant myofiber atrophy only in the primarily weight-bearing soleus muscle. Only the EDL showed unloading-induced differences in myofiber type distribution (Type II → I). These data indicate that different components of the neuromuscular system (NMJs, myofibers) respond uniquely to unloading, and that sex affects myofiber type profiles, but not NMJs. Moreover, it appears that only muscles that have their habitual activity patterns disturbed by unloading, i.e., the soleus, adapt to that intervention.