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Introduction: The ongoing emergence of SARS-CoV-2 variants poses significant challenges to existing therapeutics. The spike (S) glycoprotein is central to both viral entry and cell-to-cell transmission via syncytia formation, a process that confers resistance to neutralizing antibodies. The mechanisms underlying this resistance, particularly in relation to spike-mediated fusion, remain poorly understood. Methods: We analyzed two clinical SARS-CoV-2 isolates differing by a single amino acid substitution in the S protein. Using biochemical and cell-based assays, we evaluated entry kinetics, syncytia formation, and the neutralizing efficacy of convalescent sera. These parameters were further correlated with S-mediated cell-cell fusion activity. Results: The single amino acid substitution significantly altered entry kinetics and enhanced syncytia formation. This modification did not diminished the neutralizing capacity of convalescent sera, but it increased the efficiency of S-induced cell-cell fusion. These findings highlight the mutation's impact on viral transmissibility and immune evasion. Discussion: Our study demonstrates that even minor changes in the S protein can profoundly influence SARS-CoV-2 transmissibility and resistance to antibody-mediated neutralization. Understanding the molecular basis of S-mediated cell-cell fusion is crucial for anticipating the impact of emerging variants and developing next-generation therapeutic strategies. These insights provide a framework for predicting variant fitness and optimizing treatment approaches against future SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Men who have sex with men (MSM) and people with HIV are at increased risk of anal HPV infection and cancer. This study aimed to assess the prevalence of anal HPV among MSM with HIV (MWH) and without HIV (MWoH), as well as among MSM under and over 35 years. Factors associated with infection from high-risk (HR) HPV were investigated. This retrospective cohort analysis included MSM receiving care at IRCCS San Raffaele, Milan, Italy, with at least one HPV test collected from 2014 to 2023. Among 1577 MSM, 1427 (90%) were MWH. At first screening, 87.6% were had HR-HPV and MWoH were significantly younger, as compared to MWH. Cytological abnormalities were more frequent among younger MSM, while high-grade lesions were more frequent among those over 35 years of age. In multivariate regressions, the risk of ≥1 HR-HPV genotype at first and last screening was associated with younger age (adjusted odds ratio, aOR (95% confidence interval): 0.33 (0.18, 0.59); 0.34 (0.18, 0.58), p < 0.001) and concomitant STI (aOR 2.74 (1.59, 5.08), p < 0.001; 1.68 (1.09, 2.67), p: 0.023). A discrepancy between the recommend and actual age for screening was found. As a younger age and concomitant STIs were associated with infection by ≥1 HR-HPV, we promote a more tailored screening approach for both MWH and MWoH. [ABSTRACT FROM AUTHOR]

Background 4CMenB appears to be effective in reducing Neisseria gonorrhoeae (Ng) infections. Aims are to assess factors associated with breakthrough rectal Ng after 4CMenB and evaluate clinical and microbiological characteristics of breakthrough infections compared with before vaccination. Methods This was a retrospective study of gay, bisexual, and other men who have sex with men (GBMSM) vaccinated with 4CMenB (2 doses) between 2017 and 2023 at the San Raffaele Scientific Institute for Research, Hospitalization and Healthcare (IRCCS San Raffaele Scientific Institute), Milan, Italy, and tested for rectal Ng. Rectal Ng infection is considered breakthrough if it occurs >1 month after the second 4CMenB dose and with positive nucleic acid amplification test (NAAT) result. Follow-up was from July 2017 (first 4CMenB vaccination) to November 2023 (data freeze). Rectal Ng was screened with both NAAT and gonococcal-specific cultures. Characteristics of individuals with or without breakthrough Ng and of Ng infections before or after 4CMenB were compared using Mann-Whitney and χ2/Fisher tests. Results Overall, 473 GBMSM vaccinated with 4CMenB were included, with a median age (interquartile range) of 43 (37–51) years; 451 of 473 were living with human immunodeficiency virus. The percentage of NAAT-positive rectal Ng swab samples was 76 of 957 (7.7%) after 4CMenB and 51 of 456 (11.1%) before. Breakthrough rectal Ng after baseline were 76 in 57 of 473 people. People with rectal Ng after 4CMenB were younger, more likely to have a previous sexually transmitted infection, and had more sexual partners than those without (all P <.001). Breakthrough rectal Ng infections were less frequently symptomatic (34.2% vs 66.7%; P =.001) and more likely with negative gonococcal-specific culture (55.3% vs 19.6%; P <.001) compared with before vaccination. Conclusions Breakthrough rectal Ng infections after 4CMenB were 76 in 57/473 people, preferentially identified in GBMSM with higher-risk sexual behaviors, were less often symptomatic, and more often with negative gonococcal-specific cultures, suggesting lower infection virulence. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to estimate the effectiveness of original and bivalent COVID-19 vaccines in reducing COVID-19-associated hospitalizations among the adult population of Turin, Italy. Methods: We conducted a retrospective, test-negative, case–control study of 5768 adults aged ≥50 years who had symptoms that were consistent with COVID-19-like illness and were admitted to the hospitals of the Turin Health Unit network from 1 January 2021 to 31 January 2023. We evaluated the effectiveness of the vaccines that at the time of the study were authorized in the European Union (original/bivalent BNT162b2; original mRNA-1273; ChAdOx1-S; Ad26.COV2.S) by comparing the odds of a positive test for SARS-CoV-2 in vaccinated patients with the odds of a positive test in unvaccinated patients. The association between vaccination status, hospitalization, ICU admission and positive SARS-CoV-2 test was estimated by building multivariate adjusted logistic regression models. Results: During the predominance of the pre-Omicron variants, the vaccine effectiveness of two and three doses received in the last 120 days against COVID-19-associated hospitalizations was 93.6% (95% CI: 90.1 to 95.9) and 97.1% (95% CI: 90.8 to 99.1), respectively. During the predominance of the Omicron variant, the vaccine effectiveness of two and three doses was 26.6% (95% CI: −0.6 to 46.5) and 75.2% (95% CI: 68.1 to 80.7), respectively, and it rose to 88% (95% CI: 78.2 to 93.3) for four or five doses of the bivalent vaccine. Conclusions: Our study confirms that the COVID-19 vaccines protect adult patients from hospitalizations, including the subgroup ≥80 years, also during the period of the Omicron variant's predominance. [ABSTRACT FROM AUTHOR]

Author(s): Roberto Burioni; Anna Odone; Carlo Signorelli Italy's experience of mandatory vaccination could complement the latest French case study you discuss (see ). It provides insight into why such a [...]