No abstract

Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots. Their impact on viral infection, transmission, and efficacy of vaccines and therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. and XBB.1 variants bind ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1 and XBB.1 RBDs bound to human ACE2 and S309 Fab (sotrovimab parent) explain the altered ACE2 recognition and preserved antibody binding through conformational selection. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1, the variant displaying the greatest loss of neutralization. Moreover, in several donors vaccine-elicited plasma antibodies cross-react with and trigger effector functions against Omicron variants despite reduced neutralizing activity. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring persistent immune imprinting. Our findings suggest that this previously overlooked class of cross-reactive antibodies, exemplified by S309, may contribute to protection against disease caused by emerging variants through elicitation of effector functions.

Background: In the last years there has been an intense technological development of robotic devices for gait rehabilitation in spinal cord injury (SCI) patients. The aim of the present study was to evaluate energy cost and psychological impact during a rehabilitation programme with two different types of robotic rehabilitation systems (stationary system on treadmill, Lokomat and overground walking system, Ekso GT). Methods: Fifteen SCI patients with different injury levels underwent robot-assisted gait training sessions, divided into 2 phases: in the first phase all subjects completed 3 sessions both Lokomat and Ekso GT. Afterwards, participants were randomly assigned to Lokomat or the Ekso for 17 sessions. A questionnaire, investigating the Subjective Psychological Impact (SPI) during gait training, was administrated. The functional outcome measures were oxygen consumption (VO2), carbon dioxide production (VCO2), Metabolic Equivalent of Task (MET), walking economy, and heart rate (HR). Results: The metabolic responses (7.73 ± 1.02 mL/kg/min) and MET values (3.20 ± 1.01) during robotic overground walking resulted higher than those during robotic treadmill walking (3.91 ± 0.93 mL/kg/min and 1.58 ± 0.44; p < 0.01). Both devices showed high scores in emotion and satisfaction. Overground walking resulted in higher scores of fatigue, mental effort and discomfort while walking with Lokomat showed a higher score in muscle relaxation. All patients showed improvements in walking economy due to a decrease of energy cost with increased speed and workload. Conclusions: Overground robotic assisted gait training in rehabilitation programmePowered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation needs higher cognitive and cardiovascular efforts than robot-assisted gait training on treadmill. Response to Reviewers:Authors' answers to Reviewers Neurological SciencesWe warmly thank Reviewers for helpful comments and criticisms. Note for reviewing purposes -Our comments/answers in bold italic Revisions and corrections in the text all in red bold Reviewer #1: The revision is satisfying. We thank the Reviewer for her/his positive comment.Reviewer #2: Dear authors, the paper addresses a current topic that has been well developed.However, I suggest some changes to be made. We thank the Reviewer for his positive comment.

The WBVT does not appear to require a long time of recovery and leads to less feeling of fatigue, whereas AER needs an appropriate recovery time after the training session.