Background: Recovery in acute respiratory syndrome (ARDS) survivors developing intensive care unit-acquired weakness (ICUAW) remains uncertain.

Objectives: To identify subgroups of ARDS survivors with different ICUAW pathogenesis and long-term prognosis, using transcriptomics at ICU admission.

Methods: Consecutive COVID-19 ARDS patients were recruited at ICU admission and followed-up during hospital stay, at 3 (3mo) and 6 (6mo) months after discharge. Whole-blood transcriptomes were obtained at admission. Duke Activity Status Index -DASI-, handgrip strength (HGS), sit-to-stand test (STS) and quadriceps ultrasound, were collected as muscle-performance features. Latent class analysis (LCA) was performed to identify subgroups with different recovery capacity.

Results: 89 survivors completed follow-up (64 [57-71] year-old, 23.59% female). Diagnosis of ICUAW at discharge (n=55, 61.8%) was related to longer ICU stay (19 [10.5-31.5] versus 9.5 [6-13] days, p<0.0001) and time on ventilator (15[9-27] versus 7 [3.25-11] days, p<0.0001). Muscle-performance differed between ICUAW and non-ICUAW patients at 3mo, but not at 6mo, and no differentially expressed genes were found. LCA revealed two classes (?persistent weakness? [n=29, 33%] and ?strength recovery? [n=60]), with no differences in baseline or in-hospital clinical variables. We identified 22 differentially expressed genes (adjusted p-value cut-off=0.05) between classes, related to immune response, regulation of ion transport, muscle morphogenesis and transmission of nerve impulse.

Conclusions: Transcriptomics at ICU admission may help to identify pathogenetic molecular mechanisms leading to persistent muscle weakness in ARDS survivors.