Malignant salivary gland tumors: agreement between fine needle aspiration biopsy, incisional biopsy and final histopathological diagnostic / Tumores malignos de glándulas salivales: concordancia entre biopsia por aspiración con aguja fina, biopsia incisional y diagnóstico histopatológico final

Background: Incisional biopsy is indicated for intraoral tumors, but it is a contraindicated surgical procedure formajor salivary glands. To avoid complications and facilitate diagnosis, fine needle aspiration biopsy (FNAB) is atype of biopsy widely used for preoperative diagnosis in these glands.Material and Methods: The aim of this study was to analyze the agreement between the diagnosis by FNAB (ma-jor glands), incisional biopsy (minor glands) and histopathological analysis of the surgical specimen in salivarygland tumors from a database (medical records) of patients treated in a cancer treatment reference center in theNortheast region of Brazil.Results: The sample consisted of 110 cases, being 86 of them malignant tumors in major salivary glands (parotidgland=73; submandibular gland=13) and 24 cases in minor salivary glands (palate). The female gender was themost affected (57.3%), especially in patients over 60 years (42.7%). In the TNM classification, 41.8% of the caseswere in T2 at the time of diagnosis, with most of the regional lymph nodes in N0 (85.5%) and 87.3% of the casesin M0. FNAB was able to identify malignant neoplasms in 68.6% of the cases (n=59), while incisional biopsy inpalatal tumors obtained agreement of 75% of the cases (n=18). The analysis revealed that tumors classified as T3-T4 (p=0.012) showed greater agreement between pre- and post-surgical diagnosis.(AU)

Prevalence of bruxism among college students: what are the associated factors? A cross-sectional study

Evaluate the prevalence of bruxism and to analyze what are the possible associated factors with this condition in students of a Brazilian university. Methods: This was a cross-sectional study, with a sample of 230 students randomly selected among undergraduate courses at a university center. The dependent variable was the presence of awake bruxism and sleep bruxism. The independent variables were sociodemographic factors, smoking, alcohol consumption, oral habits and stress perception (Perceived Stress Scale- PSS 14). Descriptive statistics and bivariate analysis were used. Results: The prevalence of awake bruxism was 28.7% and was associated with the independent variables: course (degree program), gum chewing habits, chin hand placing, facedown sleeping and one-side biting. Sleep bruxism had a 7.0% prevalence and displayed association with gum chewing, pens/pencils/objects biting, tongue/lips/cheeks biting, nails biting and one-side biting. Perceived stress was not associated with either type of bruxism. Conclusion: Bruxism has an important prevalence among university students, especially when distinguishing between awake bruxism and sleep bruxism

SARS-CoV-2 evolution and patient immunological history shape the breadth and potency of antibody-mediated immunity

Since the emergence of SARS-CoV-2, humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralisation responses against SARS-CoV-2Wuhan, SARS-CoV-2, SARS-CoV-2{delta} and SARS-CoV-2o pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2Wuhan, SARS-CoV-2 or SARS-CoV-2{delta}, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design. Author SummaryNeutralising antibodies provide protection against viruses and are generated because of vaccination or prior infections. The main target of anti-SARS-CoV-2 neutralising antibodies is a protein called Spike, which decorates the viral particle and mediates viral entry into cells. As SARS-CoV-2 evolves, mutations accumulate in the spike protein, allowing the virus to escape antibody-mediated immunity and decreasing vaccine effectiveness. Multiple SARS-CoV-2 variants have appeared since the start of the COVID-19 pandemic, causing various waves of infection through the population and infecting-in some cases-people that had been previously infected or vaccinated. Since the antibody response is highly specific, individuals infected with different variants are likely to have different repertoires of neutralising antibodies. We studied the breadth and potency of the antibody-mediated response against different SARS-CoV-2 variants using sera from vaccinated people as well as from people infected with different variants. We show that potency of the antibody response against different SARS-CoV-2 variants depends on the particular variant that infected each person, the exposure type (infection or vaccination) and the number and order of exposures. Our study provides insight into the interplay between virus evolution and immunity, as well as important information for the development of better vaccination strategies.

The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron, the fifth VOC to be described, harbours 30 amino acid mutations in spike including 15 in the receptor-binding domain. Here, we demonstrate substantial evasion of neutralisation by Omicron in vitro using sera from vaccinated individuals. Importantly, these data are mirrored by a substantial reduction in real-world vaccine effectiveness that is partially restored by booster vaccination. We also demonstrate that Omicron does not induce cell syncytia and favours a TMPRSS2-independent endosomal entry pathway. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

Recurrent emergence and transmission of a SARS-CoV-2 Spike deletion ΔH69/V70

SARS-CoV-2 amino acid replacements in the receptor binding domain (RBD) occur relatively frequently and some have a consequence for immune recognition. Here we report recurrent emergence and significant onward transmission of a six-nucleotide out of frame deletion in the S gene, which results in loss of two amino acids: H69 and V70. We report that in human infections {Delta}H69/V70 often co-occurs with the receptor binding motif amino acid replacements N501Y, N439K and Y453F, and in the latter two cases has followed the RBD mutation. One of the {Delta}H69/V70+ N501Y lineages, now known as B.1.1.7, has undergone rapid expansion and includes eight S gene mutations: RBD (N501Y and A570D), S1 ({Delta}H69/V70 and {Delta}144) and S2 (P681H, T716I, S982A and D1118H). In vitro, we show that {Delta}H69/V70 does not reduce serum neutralisation across multiple convalescent sera. However, {Delta}H69/V70 increases infectivity and is associated with increased incorporation of cleaved spike into virions. {Delta}H69/V70 is able to compensate for small infectivity defects induced by RBD mutations N501Y, N439K and Y453F. In addition, replacement of H69 and V70 residues in the B.1.1.7 spike reduces its infectivity and spike mediated cell-cell fusion. Based on our data {Delta}H69/V70 likely acts as a permissive mutation that allows acquisition of otherwise deleterious immune escape mutations. Enhanced surveillance for the {Delta}H69/V70 deletion with and without RBD mutations should be considered as a global priority not only as a marker for the B.1.1.7 variant, but potentially also for other emerging variants of concern. Vaccines designed to target the deleted spike protein could mitigate against its emergence as increased selective forces from immunity and vaccines increase globally. HighlightsO_LI{Delta}H69/V70 is present in at least 28 SARS-CoV-2 lineages C_LIO_LI{Delta}H69/V70 does not confer escape from convalescent sera C_LIO_LI{Delta}H69/V70 increases spike infectivity and compensates for RBD mutations C_LIO_LI{Delta}H69/V70 is associated with greater spike cleavage C_LIO_LIB.1.1.7 requires {Delta}H69/V70 for optimal spike cleavage and infectivity C_LI