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Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summaryA sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.
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Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-resistant and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between "hot" immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines. One sentence summaryA third booster dose of inactivated vaccine produces a highly sifted humoral immune response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the Spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures to contain the spread of the disease in many countries has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread and whether they can cause a more severe disease remain unclear. Herein, we performed a structural investigation using molecular dynamics simulations and determined dissociation constant (KD) values using surface plasmon resonance (SPR) assays of three fastspreading SARS-CoV-2 variants, Alpha, Beta and Gamma ones, as well as genetic factors in the host cells that may be related to the viral infection. Our results suggest that the SARS-CoV-2 variants facilitate their entry into the host cell by moderately increased binding affinities to the human ACE2 receptor, different torsions in hACE2 mediated by RBD variants, and an increased Spike exposure time to proteolytic enzymes. We also found that other host cell aspects, such as gene and isoform expression of key genes for the infection (ACE2, FURIN and TMPRSS2), may have few contributions to the SARS-CoV-2 variants infectivity. In summary, we concluded that a combination of viral and host cell factors allows SARS-CoV-2 variants to increase their abilities to spread faster than wild-type. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY
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Objective The purpose of this study was to compare the self-evaluation and doctor-patient orientation between medical students and residents before the courses in different communication sections,and gave guide to different objects for their targeted teaching.Methods We set a sample made of 331 medical students and 308 residents who were trained in Clinical communication skills course in Peking Union Medical College from Oct.2009 to Oct.2013.Before the course,they were investigated by two self-assessment questionnaires.One is communication skills and occupation practice confidence;the other is doctor-patient orientation.Their result data were analyzed and handled by SPSS 17.0 software,adopting an independent samples t test.Results The order of the different aspects of doctor patient communication skills was same in two groups,gathering complete history [(4.340 ± 0.756) vs.(4.050 ± 0.707)] first,and establishing good doctor patient relationship [(4.310 ±0.740) vs.(4.030 ±0.790)],discussing a therapeutic plan with patient [(4.050 ± 0.812) vs.(3.600 ± 0.823)],informing bad news [(3.850 ± 0.897) vs.(3.260 ± 0.907)] followed.According to the self-assessment,residents were more confident than medical students in all these aspects above mentioned and establishing good doctor patient relationship.The doctorpatient orientation scale indicated that the residents group is more inclined to doctor-centric mode than the medical students group.Conclusion This study suggested that the residents is more confident in doctorpatient communication skills than medical students,while is less inclined to patient-centric mode than them.The focus of the communication teaching is similarity in the distribution of the two groups.Medical students' communication curriculum needs to take into account the limited clinical experiences,and training for residents needs to emphasize the capacity of empathy and perspective-taking.
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Humanistic doctor-patient communication is an essential capability for medical workers and is as impor -tant as medical technology .Its education has been getting more and more attention in recent years .However , the training and evaluation of humanistic doctor-patient communication as a practical other than theoretical capability has been difficult .A new method , clinical scenery drama , based on psychodrama and role theory , is developed by Dept.of Psychological Medicine , Peking Union Medical College Hospital from recent 10 years of medical doctor and student training .In clinical scenery drama , medical students are thrown to different roles to empathize with their feelings and conflicts , try to resolve clinical dilemma with humanistic communication technique besides medi-cal technology .Then the sharing and comments from teachers and observers help students to understand the situa -tion from other perspectives and think about other possible solutions .
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Cascading failures have become major threats to network robustness due to their potential catastrophic consequences, where local perturbations can induce global propagation of failures. Unlike failures spreading via direct contacts due to structural interdependencies, overload failures usually propagate through collective interactions among system components. Despite the critical need in developing protection or mitigation strategies in networks such as power grids and transportation, the propagation behavior of cascading failures is essentially unknown. Here we find by analyzing our collected data that jams in city traffic and faults in power grid are spatially long-range correlated with correlations decaying slowly with distance. Moreover, we find in the daily traffic, that the correlation length increases dramatically and reaches maximum, when morning or evening rush hour is approaching. Our study can impact all efforts towards improving actively system resilience ranging from evaluation of design schemes, development of protection strategies to implementation of mitigation programs.