SARS-CoV-2 variants, spike mutations and immune escape.

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of 'variants of concern', that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1

The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1(+) NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro. Activation of CD4(+) T cells triggered the transcription and surface expression of HLA-F mRNA and HLA-F protein, respectively, and induced binding of KIR3DS1. HIV-1 infection further increased the transcription of HLA-F mRNA but decreased the binding of KIR3DS1, indicative of a mechanism for evading recognition by KIR3DS1(+) NK cells. Thus, we have established HLA-F as a ligand of KIR3DS1 and have demonstrated cell-context-dependent expression of HLA-F that might explain the widespread influence of KIR3DS1 in human disease

HLA-Fatal attraction.

International audienceOpen conformers of the non-classical and monomorphic major histocompatibility complex (MHC) class I molecule HLA-F are ligands for the activating receptor KIR3DS1 and trigger the activation of natural killer (NK) cells

Does the COVID‐19 seroconversion in older adults resemble the young?

High antibody titers have been found to correlate with the severity of coronavirus disease 2019 (COVID‐19) disease. Therefore, antibody titers may be higher in older adults, whose disease is known to have a more severe course than younger ones. This study aimed to compare the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) immunoglobulin G (IgG) antibody level in the reverse transcription‐polymerase chain reaction (RT‐PCR) to test positive older adults with young. Patients aged ≥18 with positive RT‐PCR and checked serum IgG antibodies between November 1, 2020 and January 13, 2021 were included. The IgG antibody levels and the time between RT‐PCR positivity with the antibody levels were recorded. A total of 1071 patients were divided into two groups as Group 1 <60 years old (n = 902) and Group 2 ≥60 years old (n = 169). The SARS‐CoV‐2 IgG antibody titers were higher in Group 2 (p = 0.001). This height was present in the first 3 months after positive RT‐PCR. While the antibody titers were compared by dividing Group 2 into the three groups according to age ranges (60–69, 70–79, and ≥80 years), the antibody titer was higher in ≥80 years patients (p = 0.044). High COVID‐19 IgG antibody levels may be associated with the severity of the disease. Also, the humoral immunity advantage was seen in the first 3 months in the older patients, which suggests that older adults with COVID‐19 may develop reinfection in the long term