Structural basis of spike RBM-specific human antibodies counteracting broad SARS-CoV-2 variants.

The decrease of antibody efficacy to mutated SARS-CoV-2 spike RBD explains the breakthrough infections and reinfections by Omicron variants. Here, we analyzed broadly neutralizing antibodies isolated from long-term hospitalized convalescent patients of early SARS-CoV-2 strains. One of the antibodies named NCV2SG48 is highly potent to broad SARS-CoV-2 variants including Omicron BA.1, BA.2, and BA.4/5. To reveal the mode of action, we determined the sequence and crystal structure of the Fab fragment of NCV2SG48 in a complex with spike RBD from the original, Delta, and Omicron BA.1. NCV2SG48 is from a minor VH but the multiple somatic hypermutations contribute to a markedly extended binding interface and hydrogen bonds to interact with conserved residues at the core receptor-binding motif of RBD, which efficiently neutralizes a broad spectrum of variants. Thus, eliciting the RBD-specific B cells to the longitudinal germinal center reaction confers potent immunity to broad SARS-CoV-2 variants emerging one after another.

Vaccination with the Omicron spike RBD boosts broadly neutralizing antibody levels and confers sustained protection even after acquiring immunity to the original antigen.

The immune evasion of SARS-CoV-2 Omicron variants caused by multiple amino acid replacements in the receptor-binding domain (RBD) of the spike protein wanes the effectiveness of antibodies elicited by current SARS-CoV-2 booster vaccination. The vaccines that target Omicron strains have been recently developed, however, there has been a concern yet to be addressed regarding the negative aspect of the immune response known as original antigenic sin. Here, we demonstrate that the breadth of neutralizing antibodies against SARS-CoV-2 variants is barely elicited by immunizing monovalent viral antigens via vaccination or natural infection in mice and human subjects. However, vaccination of Omicron BA.1 RBD to pre-immunized mice with the original RBD conferred sustained neutralizing activity to BA.1 and BA.2 not only original pseudoviruses. The acquisition of neutralizing antibody breadth was further confirmed in vaccinated-then-Omicron convalescent human sera in which neutralizing activity against BA.1 and BA.2 pseudoviruses was highly induced. Thus, our data suggest that Omicron-specific vaccines or the infection with Omicron viruses can boost potent neutralizing antibodies to the Omicron variants even in the host pre-vaccinated with the original antigen.

Socio-environmental factors associated with diabetes mellitus among patients hospitalized with schizophrenia in Japan.

OBJECTIVE: This study aimed to examine epidemiologically socio-environmental factors associated with diabetes mellitus among patients hospitalized with schizophrenia in Japan. METHODS: This was a cross-sectional study from a single psychiatric hospital. Study patients were adults aged ≥20 years who were hospitalized with schizophrenia one or more times between January 2013 and December 2014. From electronic medical records or health insurance claims, we extracted schizophrenia patients with an F2 code according to ICD-10, and assessed the association of various factors with diabetes mellitus among these patients in a multivariable analysis. RESULTS: During the 2-year period, there were 1899 patients hospitalized with a psychiatric disorder one or more times. Of them, a total of 770 adults with schizophrenia (285 men and 485 women) were eligible for our analysis. The standardized prevalence ratio of diabetes mellitus was 2.0 [95 % confidence interval (CI) 1.6-2.5] among men and 3.0 (95 % CI 2.5-3.6) among women in this hospital. There were no socio-environmental factors associated with diabetes mellitus among men. Among women, factors such as a 730-day hospitalization [adjusted odds ratio (OR) 3.82: 95 % confidence interval (CI) 1.52-9.64], and a medical protection/compulsory/discrimination hospitalization (adjusted OR 0.60, 95 % CI 0.36-0.99) were associated with diabetes mellitus. Compared with women living alone, those who were unmarried and lived together with someone had a significantly lower adjusted OR (0.41, 95 % CI 0.21-0.81). CONCLUSIONS: Socio-environmental factors such as length of hospitalization, type of hospitalization, and marital status and living arrangement were associated with diabetes mellitus among hospitalized women with schizophrenia.