Spike mutations in SARS-CoV-2 variants confer resistance to antibody neutralization

New SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS-CoV-2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N-E484K-N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

Analysis of 1019 cases with rabies exposure and prophylaxis / 中华实验和临床病毒学杂志

Objective@#To understand the prophylaxis of population exposed to rabies, and provide a basis for prevention and control of rabies.@*Methods@#The registration data of 1 019 cases with rabies exposure in Beijing Ditan Hospital Affiliated to Capital Medical University from Mar, 2017 to Feb, 2018 were analyzed using the descriptive epidemiologic method.@*Results@#Among the 1 019 cases of rabies exposure, the sex ratio of men to women was 0.90∶1, with the highest proportion of them were between 26 and 46 years of age old, accounting for 46.5%. Rabies exposure reached its peak (46.9%) between June and September. In addition, 63.3% of the injuries were caused by dogs and 36.7% by cats. Most of the wounds (55.1%) occurred in hands; and the second was lower limbs (26.6%). Most of the cases (60.7%) had grade II wounds; followed by grade III wounds (39.1%); 69.3% of the cases completed immunization with rabies vaccine. In grade III exposure, 73.7% of the patients were immunized with rabies immunoglobulin. Most of the persons of grade III exposure (73.7%) received inoculation with human rabies immunoglobulin (HRIG).@*Conclusions@#Measures to control rabies should be focused on the management of dogs and cats and the standardization of rabies post-exposure prophylaxis.

Analysis of clinical treatment of dual exposure to rabies virus and HIV in an incident with multi-victims bitten by a dog / 中华实验和临床病毒学杂志

Objective@#To analyze the clinical response in cases of multi-victims bitten by a dog in Beijing (one of whom was HIV positive), and to explore the route and prognosis of dual exposure to rabies virus and HIV.@*Methods@#Descriptive epidemiological methods were used to analyze the exposed cases, the post-exposure prophylaxis(PEP) of rabies and HIV and the follow-up outcomes.@*Results@#After six months-follow up, there was no rabies case was found among those nine victims bitten by the suspected dog. In addition, six HIV-negative victims who had been exposed to HIV via dog saliva were consistently tested to be HIV negative in the follow up period.@*Conclusions@#In cases with multi-victims bitten by one dog, except exposure to rabies virus, it is necessary to be alert to the presence of HIV, HBV or HCV infection in sequential victims. Therefore, the risk of the potential spreading of other blood-borne infectious pathogens should be assessed. It is important to initiate PEP as early as possible.

The effect of HIV infection and HAART on mitochondrion in peripheral monocytes / 中华检验医学杂志

Objective To evaluate the effect of HIV infection and highly active antiretroviral therapy (HAART) on mitochondrial function and mass in peripheral monocytes.Methods There were 14 ART-naive HIV-infected patients,14 NRTI treated HIV-infected patients and 12 healthy controls from Beijing Ditan Hospital.The mitochondrial membrane potential and mitochondrial mass in monocytes were analyzed by flow cytometry.Mitochondrial disturbances related to HIV infection and HAART in monocytes were analyzed.Results In ART-naive patients and NRTI-exposed patients,the levels of mitochondrial membrane potential in monocytes (77.74 ± 14.77,73.94 ± 12.87) were significantly lower than these in healthy controls (89.43 ±4.06) (P =0.032 8,P =0.002 6).The amount of mitochondrial mass in NRTI-exposed patients (3 329.0 ± 836.7) was significantly higher than that in healthy controls (2 075.0 ± 932.2) and that in ART-naive patients (2 592.0 ± 781.5) (P ＜ 0.05).Conclusions The abnormal of mitochondrial membrane potential and mitochondrial mass in monocytes from HIV-infected patients were related to HIV infection and the introduction of HAART.