Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by its surface glycoprotein, Spike. The S1 subunit of Spike contains the N-terminal domain (NTD) and the receptor-binding domain (RBD), which mediates recognition of the host cell receptor angiotensinconverting enzyme 2 (ACE2). The S2 subunit drives fusion

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.

Purpose To report our 11-year minimum clinical and radiological outcomes, as well as complications of the Charite III total disc replacement (TDR). Methods A total of 35 patients indicated for total disc replacement were implanted with the Charite III prosthesis. Clinical evaluation included visual analog scale (VAS) for back pain and the Oswestry disability index (ODI). Radiological parameters of intervertebral disc height (IDH), range of motion (ROM), lumbar lordosis, lumbar scoliosis and prosthesis position were evaluated. Complications and reoperation rates were also assessed. Results Thirty-two patients had a minimum 11-year follow-up, and 33 prostheses were implanted. The mean follow-up time was 11.8 years, ranging from 11.3 to 13.8 years. Twenty-eight patients (87.5 %) had a successful outcome, as defined by the FDA. Reoperation was performed in 2 patients for adjacent segment degeneration and pedicle fracture (1 case each). Both VAS and ODI scores showed significant improvement compared to baseline. At the final follow-up, the ROM of both the index-and adjacent-level showed an obvious decrease. The IDH of the index level showed a tendency to decrease, but the difference was not significant. The IDH of adjacent levels were not significantly affected by the surgery. Mean lumbar lordosis was increased at the final follow-up, and lumbar scoliosis over 3°was observed in 12 patients (37.5 %), with a mean angle of 5.6°(range 3°-12°). Of all 35 prostheses, 15 were left-shifted, 3 were right-shifted and 14 were just in the middle. In the coronal plane, 25 were rated as ideally placed, 5 were discretely shifted, 4 were slightly shifted and 1 was markedly shifted. In the sagittal plane, only 12 prostheses were rated as ideally placed, 14 were discretely shifted and 9 were suboptimally placed. Prosthesis subsidence was noted in 3 (9.4 %) patients (the subsidence distances were 3.1, 4.2 and 2.8 mm, respectively). Heterotopic ossification was detected in 25 segments (71.4 %), consisting of Class-I heterotopic ossification in 7 segments (20.0 %), Class-II in 9 segments (25.7 %), and Class-III in 9 segments (25.7 %). Class-IV heterotopic ossification was not observed. Conclusion The cumulative survival was 100 % at a mean follow-up of 11.8 years. Clinical and radiological results were satisfactory and long-term clinical results were maintained for a mean follow-up of 11.8 years. Reoperation and complication rates are acceptable, and our study does not substantiate the fear of reoperation or late complications. The results of our long-term follow-up indicate that, with strict indication, TDR is a safe and effective procedure as an alternative to lumbar fusion.

Study design A retrospective study. Objective To evaluate the different degeneration patterns of paraspinal muscles in degenerative lumbar diseases and their correlation with lumbar spine degeneration severity. Summary of background data The degeneration characteristics of different paraspinal muscles in degenerative lumbar diseases remain unclear. Methods 78 patients diagnosed with single-level degenerative lumbar spondylolisthesis (DLS) and 76 patients with degenerative lumbar kyphosis (DLK) were included as DLS and DLK groups. Paraspinal muscle parameters of psoas major (PS), erector spinae (ES) and multifidus muscle (MF) were measured, including fatty infiltration (FI) and relative cross-sectional area (rCSA), namely the ratio of the paraspinal muscle CSA to the CSA of the vertebrae of the same segment. Sagittal parameters including lumbar lordosis (LL) and sagittal vertical axis (SVA) were measured. The paraspinal muscle parameters and ES/MF rCSA ratio were compared between the two groups. Paraspinal muscles parameters including rCSA and FI were also compared between each segments from L1 to L5 in both DLS and DLK groups. In order to determine the influence of sagittal spinal alignment on paraspinal muscle parameters, correlation analysis was conducted between the MF, ES, PS rCSA and FI and the LL in DLS and DLK group. Result MF atrophy is more significant in DLS patients compared with DLK. Also, MF fatty infiltration in the lower lumbar spine of DLS patients was greater compared to DLK patients. DLK patients showed more significant atrophy of ES and heavier ES fatty infiltration. MF FI was significantly different between all adjacent segments in both DLS and DLK groups. In DLS group, ES FI was significantly different between L2/L3 to L3/L4 and L4/L5 to L5/S1, while in DLK group, the difference of ES FI between all adjacent segments was not significant, and ES FI was found negatively correlated with LL. Conclusions Paraspinal muscles show different degeneration patterns in degenerative lumbar diseases. MF degeneration is segmental in both DLS and DLK patients, while ES degenerated diffusely in DLK patients and correlated with the severity of kyphosis. MF degeneration is more significant in the DLS group, while ES degeneration is more significant in DLK patients. MF is the stabilizer of the lumbar spine segments, while the ES tends to maintain the spinal sagittal balance.