Post-acute immunological and behavioral sequelae in mice after Omicron infection.

Progress in understanding long COVID and developing effective therapeutics is hampered in part by the lack of suitable animal models. Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection to test for pulmonary and behavioral post-acute sequelae. Through in-depth phenotyping by CyTOF, we demonstrate that naïve mice experiencing a first Omicron infection exhibit profound immune perturbations in the lung after resolving acute infection. This is not observed if mice were first vaccinated with spike-encoding mRNA. The protective effects of vaccination against post-acute sequelae were associated with a highly polyfunctional SARS-CoV-2-specific T cell response that was recalled upon BA.1 breakthrough infection but not seen with BA.1 infection alone. Without vaccination, the chemokine receptor CXCR4 was uniquely upregulated on multiple pulmonary immune subsets in the BA.1 convalescent mice, a process previously connected to severe COVID-19. Taking advantage of recent developments in machine learning and computer vision, we demonstrate that BA.1 convalescent mice exhibited spontaneous behavioral changes, emotional alterations, and cognitive-related deficits in context habituation. Collectively, our data identify immunological and behavioral post-acute sequelae after Omicron infection and uncover a protective effect of vaccination against post-acute pulmonary immune perturbations.

Impact of ankle foot orthosis stiffness on Achilles tendon and gastrocnemius function during unimpaired gait.

Ankle foot orthoses (AFOs) are designed to improve gait for individuals with neuromuscular conditions and have also been used to reduce energy costs of walking for unimpaired individuals. AFOs influence joint motion and metabolic cost, but how they impact muscle function remains unclear. This study investigated the impact of different stiffness AFOs on medial gastrocnemius muscle (MG) and Achilles tendon (AT) function during two walking speeds. We performed gait analyses for eight unimpaired individuals. Each individual walked at slow and very slow speeds with a 3D printed AFO with no resistance (free hinge condition) and four levels of ankle dorsiflexion stiffness: 0.25Nm/°, 1Nm/°, 2Nm/°, and 3.7Nm/°. Motion capture, ultrasound, and musculoskeletal modeling were used to quantify MG and AT lengths with each AFO condition. Increasing AFO stiffness increased peak AFO dorsiflexion moment with decreased peak knee extension and peak ankle dorsiflexion angles. Overall musculotendon length and peak AT length decreased, while peak MG length increased with increasing AFO stiffness. Peak MG activity, length, and velocity significantly decreased with slower walking speed. This study provides experimental evidence of the impact of AFO stiffness and walking speed on joint kinematics and musculotendon function. These methods can provide insight to improve AFO designs and optimize musculotendon function for rehabilitation, performance, or other goals.