Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants.

Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines1,2. Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine.

Suboptimal declines and delays in early breast cancer treatment after COVID-19 quarantine restrictions in China: A national survey of 8397 patients in the first quarter of 2020.

BACKGROUND: Cancer patients had been profoundly affected by the outbreak of COVID-19 especially after quarantine restrictions in China. We aimed to explore the treatment changes and delays of early breast cancer (EBC) during the first quarter of 2020. METHODS: We did this retrospective, multicentre, cohort study at 97 cancer centres in China. EBC patients who received treatment regardless of preoperative therapy, surgery or postoperative therapy during first quarter of 2020 were included. FINDINGS: 8397 patients were eligible with a median age of 50 (IQR 43-56). 0·2% (15/8397) of EBC patients were confirmed as COVID-19 infection. Only 5·2% of breast cancer diagnosis occurred after quarantine in Hubei compared with 15·3% in other provinces (OR= 0·30, 95%CI 0·24-0·38). postoperative endocrine therapy were least affected compared with different regions after quarantine (OR=0·37 [95%CI 0·19-0·73]). The proportion of surgery decreased from 16·4% in December last year to 2·6% in February in Hubei. Compared with intervals from diagnosis to treatment before quarantine restrictions, the average time increased with significance from 3·5 to 7·7 days in Hubei and 5·7 to 7·7 days in other provinces (p< 0·001). There were also 18·5 and 7·2 days delay in Hubei and other provinces respectively when calculating interval from surgery to postoperative therapy. INTERPRETATION: EBC from high risk regions had a comparative rate of COVID-19 infection. After implementation of COVID-19 quarantine restrictions, fewer diagnosis and surgery with significant delays were seen when compared with treatment before. FUNDING: Beijing Medical Award Foundation (YJ0120).