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The SARS-CoV-2 B.1.1.529 variant (Omicron) contains 15 mutations on the receptor-binding domain (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) and humoral immunity requires immediate investigation. Here, we used high-throughput yeast display screening to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs identified from SARS-CoV/SARS-CoV-2 convalescents and vaccinees. Based on the results, NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlaps with ACE2-binding motif, are largely escaped by K417N, N440K, G446S, E484A, Q493K, and G496S. Group E (S309 site) and F (CR3022 site) NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, S371L, and S375F. Furthermore, B.1.1.529 pseudovirus neutralization and RBD binding assay showed that single mutation tolerating NAbs could also be escaped due to multiple synergetic mutations on their epitopes. In total, over 85% of the tested NAbs are escaped by Omicron. Regarding NAb drugs, LY-CoV016/LY-CoV555 cocktail, REGN-CoV2 cocktail, AZD1061/AZD8895 cocktail, and BRII-196 were escaped by Omicron, while VIR7831 and DXP-604 still function at reduced efficacy. Together, data suggest Omicron could cause significant humoral immune evasion, while NAbs targeting the sarbecovirus conserved region remain most effective. Our results offer instructions for developing NAb drugs and vaccines against Omicron and future variants.

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The aim of this study was to investigate the potential role of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorders (ASD) by measuring serum circulating levels of BDNF as well as calcium and comparing them with age-matched and sex-matched normal controls. The study included 75 drug-naive ASD children and 75 age-sex-matched healthy children. The concentration of serum BDNF was determined using the enzyme-linked immunosorbent assay method at baseline. Clinical information was collected. The severity of ASD was assessed at admission using the Childhood Autism Rating Scale total score. The results indicated that the mean serum BDNF levels were significantly (P<0.0001) higher in children with ASD compared with the control cases (17.59±5.55 vs. 11.21±2.79 ng/ml; t=8.902). On the basis of the receiver operating characteristic curve, the optimal cutoff value of serum BDNF levels as an indicator for auxiliary diagnosis of autism was projected to be 12.65 ng/ml, which yielded a sensitivity of 80.8% and a specificity of 70.2%; the area under the curve was 0.840 [95% confidence interval (CI), 0.777-0.904]. In univariate logistic regression analysis, with an unadjusted odds ratio of 9.42 (95% CI, 4.33-25.95; P<0.0001), BDNF of 12.65 ng/ml or more had an association with a diagnosis of ASD. After adjusting for possible covariates, BDNF of 12.65 ng/ml or more is still an independent indicator of ASD, with an adjusted odds ratio of 7.33 (95% CI, 2.98-16.55; P<0.0001). Serum BDNF levels may be associated independently with the severity of ASD, and higher BDNF levels could be considered an independent diagnostic marker of ASD.