[Educating to properly close the toilet knob taps or to replace them]. / Educare a chiudere in modo corretto i rubinetti a manopola del bagno o a sostituirli.

Systematic reviews have shown a prevalence close to 20% of gastrointestinal symptoms in COVID-19 positive patients, with nearly 40% of patients shedding viral RNA in their faeces, even if it may not be infectious, possibly because of inactivation by colonic fluid.According to current evidence, this virus is primarily transmitted by respiratory droplets and contact routes, including contaminated surfaces. The virus is quite stable on stainless steel, being detected up to 48-72 hours after application. Therefore, some individuals can be infected touching common contaminated surfaces, such as bathroom taps. Taps can be underestimated critical points in the transmission chain of the infection. Indeed, just by turning the knob, people leave germs on it, especially after coughing over their hands, sneezing, and/or blowing their nose. After handwashing with soap, user take back their germs when turning the knob. Paradoxically, the following user collects the germs back on his/her fingers by implementing a preventive measure, maybe before putting food into the mouth or wearing contact lenses.The Italian National Institute of Health recommends to clean and disinfect high-touched surfaces, but it is unrealistic and inefficient to do so after each tap use. As an alternative, new toilets should install long elbow-levers - or at least short levers - provided that people are educated to close them with the forearm or the side of the hand. This is already a standard measure in hospitals, but it is particularly important also in high-risk communities, such as retirement homes and prisons. It would be important also in schools, in workplaces, and even in families, contributing to the prevention both of orofaecal and respiratory infections.In the meantime, people should be educated to close existing knobs with disposable paper towel wipes or with toilet paper sheets.

Ex Vivo and In Vivo CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26)

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV-1. However, its primary receptor portfolio remains controversial, potentially including sialic acid, coxsackie and adenovirus receptor (CAR), integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned on the basis of the inability to cocrystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infection in vitro and in vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domain CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild-type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (i.m.) injection but not after intranasal (i.n.) administration. Ad26 transduction was 10-fold lower than Ad5 transduction after intratumoral (i.t.) injection of CD46expressing tumors. Ad26 transduction of liver was 1,000-fold lower than that ofAd5 after intravenous (i.v.) injection. These data demonstrate the use of CD46 by Ad26 in certain situations but also show that the receptor has little consequence by other routes of administration. Finally, i.v. injection of high doses of Ad26 into CD46 mice induced release of liver enzymes into the bloodstream and reduced white blood cell counts but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during coronavirus disease 2019 (COVID-19) vaccination with this serotype of adenovirus. IMPORTANCE The human species D Ad26 is being investigated as a low-seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection and its role in virus biology, vaccine efficacy, and, importantly, vaccine safety.

Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2.

Numerous neutralizing antibodies that target SARS-CoV-2 have been reported, and most directly block binding of the viral Spike receptor-binding domain (RBD) to angiotensin-converting enzyme II (ACE2). Here, we deliberately exploit non-neutralizing RBD antibodies, showing they can dramatically assist in neutralization when linked to neutralizing binders. We identified antigen-binding fragments (Fabs) by phage display that bind RBD, but do not block ACE2 or neutralize virus as IgGs. When these non-neutralizing Fabs were assembled into bispecific VH/Fab IgGs with a neutralizing VH domain, we observed a ~ 25-fold potency improvement in neutralizing SARS-CoV-2 compared to the mono-specific bi-valent VH-Fc alone or the cocktail of the VH-Fc and IgG. This effect was epitope-dependent, reflecting the unique geometry of the bispecific antibody toward Spike. Our results show that a bispecific antibody that combines both neutralizing and non-neutralizing epitopes on Spike-RBD is a promising and rapid engineering strategy to improve the potency of SARS-CoV-2 antibodies.