COVID-19 VACCINES: EVIDENCE, CHALLENGES AND THE FUTURE

Through an unprecedented research and development process, in early 2021, just one year after the COVID-19 pandemic started devastating the world, there are several vaccines commercially available or in advanced phase of testing, each with its own characteristics and challenges. For the first time in the history of vaccination, a global immunization programme has started at a time of intense pandemic activity characterized by high virus transmission, facilitating selection of variants potentially able to escape the vaccine-induced antibody response. The reality is that one cannot rely on a single vaccine when dealing with a pandemic emergency: the urgent need of billions of doses clashes with the production capacity of the pharmaceutical industry. There is therefore no ideal vaccine, but there are many good vaccines to be used immediately. Today,  the international debate about COVID-19 vaccines is the hottest topic in global health whether it relates to technical and scientific issues or to the ethical aspects of access to vaccinations for all. This article aims at reviewing the status of vaccines that are used, or about to be used, in immunization campaigns worldwide

Clinical characterization and whole genome sequence-based typing of two cases of endophthalmitis due to Listeria monocytogenes

Endophthalmitis due to Listeria monocytogenes is an exceedingly rare cause of listeriosis. Here, we report two cases which occurred in patients with different medical history, a 46-years-old immunocompetent woman and an elderly man with several comorbidities. There was no history of trauma or surgery in either patient suggesting an endogenous origin. Despite antibiotic treatment, both patients showed poor visual acuity outcomes. Subtyping clinical isolates using whole genome sequencing could allow to identified Listeria monocytogenes strains involved in rare clinical manifestation, such as in unusual anatomical sites, even in immunocompetent patients, and could be helpful in the redefinition of the hypervirulent strains

Breakthrough Infections: A Challenge towards Measles Elimination?

Measles is one of the most contagious diseases known to man. Despite the existence of a safe and effective live attenuated vaccine, measles can appear in vaccinated individuals. Paradoxically, breakthrough cases increase as vaccination coverage in the general population rises. In measles endemic areas, breakthrough cases represent less than 10% of total infections, while in areas with high vaccination coverage these are over 10% of the total. Two different vaccination failures have been described: primary vaccination failure, which consists in the complete absence of humoral response and occurs in around 5% of vaccinated individuals; and secondary vaccination failure is due to waning immunity or incomplete immunity and occurs in 2–10% of vaccinees. Vaccination failures are generally associated with lower viral loads and milder disease (modified measles) since vaccination limits the risk of complicated disease. Vaccination failure seems to occur between six and twenty-six years after the last vaccine dose administration. This review summarizes the literature about clinical, serological, epidemiological, and molecular characteristics of measles breakthrough cases and their contribution to virus transmission. In view of the measles elimination goal, the assessment of the potential decline in antibody protection and the targeted implementation of catch-up vaccination are essential

A Methodological Approach to Water Concentration to Investigate the Presence of SARS-CoV-2 RNA in Surface Freshwaters

During the COVID-19 public health emergency, an increasing number of studies reported the occurrence of SARS-CoV-2 in wastewaters worldwide, but little is known about the presence of the virus in surface freshwaters. The aim of the current study was to develop and validate an appropriate and scalable methodological approach for the concentration and detection of SARS-CoV-2 from surface freshwater samples, collected within the Milan rural network subjected to flood spillways activity. Overall, both surface water and distilled water samples spiked with inactivated SARS-CoV-2 were used to validate the concentration method for pathogens determination. Two pre-filtration systems, filter paper and Sartolab® P20 (Sartorius, Germany) and two concentration methods, two-phase (PEG-dextran method) separation and tangential flow ultrafiltration (UF), were compared. The effects of pre-filtration and concentration on viral nucleic acid recovery were assessed through real time RT-PCR targeting SARS-CoV-2 and the internal viral control PMMoV (Pepper Mild Mottle Virus). Our results showed that UF is more sensitive than the PEG-dextran method in viral acid nucleic recovery from surface water samples. Better results were obtained pre-filtering samples with Sartolab® P20 and extracting the nucleic acids with undiluted silica, rather than diluted as required by the standard protocol. The proposed method will be used for the monitoring of surface waters in the Milan area

Evaluation of the Virulence Potential of <i>Listeria monocytogenes</i> through the Characterization of the Truncated Forms of Internalin A

Listeria monocytogenes is a widespread Gram-positive pathogenic bacterium that causes listeriosis, a rather rare but severe foodborne disease. Pregnant women, infants, the elderly, and immunocompromised individuals are considered particularly at risk. L. monocytogenes can contaminate food and food-processing environments. In particular, ready-to-eat (RTE) products are the most common source associated with listeriosis. L. monocytogenes virulence factors include internalin A (InlA), a surface protein known to facilitate bacterial uptake by human intestinal epithelial cells that express the E-cadherin receptor. Previous studies have demonstrated that the presence of premature stop codon (PMSC) mutations naturally occurring in inlA lead to the production of a truncated protein correlated with attenuate virulence. In this study, 849 L. monocytogenes isolates, collected from food, food-processing plants, and clinical cases in Italy, were typed and analyzed for the presence of PMSCs in the inlA gene using Sanger sequencing or whole-genome sequencing (WGS). PMSC mutations were found in 27% of the isolates, predominantly in those belonging to hypovirulent clones (ST9 and ST121). The presence of inlA PMSC mutations in food and environmental isolates was higher than that in clinical isolates. The results reveal the distribution of the virulence potential of L. monocytogenes circulating in Italy and could help to improve risk assessment approaches

Immunological Characterization of HIV and SARS-CoV-2 Coinfected Young Individuals

While the risk of SARS-CoV-2 infection and/or COVID-19 disease progression in the general population has been largely assessed, its impact on HIV-positive individuals remains unclear. We present clinical and immunological data collected in a cohort of HIV-infected young individuals during the first wave of COVID-19 pandemic. SARS-CoV-2 RNA, virus-specific antibodies, as well as the expression of factors involved in the anti-viral immune response were analyzed. Moreover, we set up an in vitro coinfection assay to study the mechanisms correlated to the coinfection process. Our results did not show any increased risk of severe COVID-19 in HIV-positive young individuals. In those subjects who contracted SARS-CoV-2 infection, an increase in IL-10 expression and production was observed. Furthermore, in the in vitro coinfection assay, we revealed a reduction in SARS-CoV-2 replication associated to an upregulation of IL-10. We speculate that IL-10 could play a crucial role in the course of SARS-CoV-2 infection in HIV-positive individuals. These results might help defining clinical management of HIV/SARS-CoV-2 co-infected young individuals, or putative indications for vaccination schedules in this population

Characterization of Vaccine Breakthrough Cases during Measles Outbreaks in Milan and Surrounding Areas, Italy, 2017–2021

Despite the existence of an effective live-attenuated vaccine, measles can appear in vaccinated individuals. We investigated breakthrough measles cases identified during our surveillance activities within the measles/rubella surveillance network (MoRoNet) in Milan and surrounding areas (Northern Italy). Between 2017 and 2021, we confirmed measles virus (genotypes B3 or D8) infections in 653 patients and 51 of these (7.8%) were vaccinees. Among vaccinated individuals whose serum was available, a secondary failure was evidenced in 69.4% (25/36) of cases while 11 patients (30.6%) were non-responders. Non-responders were more frequently hospitalized and had significantly lower Ct values in both respiratory and urine samples. Median age and time since the last immunization were similar in the two groups. Importantly, we identified onward transmissions from vaccine failure cases. Vaccinees were involved in 20 outbreaks, in 10 of them they were able to transmit the virus, and in 8 of them, they were the index case. Comparing viral hemagglutinin sequences from vaccinated and non-vaccinated subjects did not show a specific mutation pattern. These results suggest that vaccination failure was likely due to the poor immune response of single individuals and highlights the importance of identifying breakthrough cases and characterizing their clinical and virologic profiles

Listeria monocytogenes Transmission from Donated Blood to Platelet Transfusion Recipient, Italy

We report Listeria monocytogenes infection in a patient in Italy who was transfused with pooled platelet concentrate. Genomic analysis revealed that L. monocytogenes isolates from the donor blood unit, the transfused platelets, and the patient’s blood culture were genetically closely related, confirming transfusion transmission. Additional surveillance and secondary bacterial screening could improve transfusion safety

Preschool-located influenza vaccination and influenza-like illness surveillance: an Italian pilot experience

Abstract Background We describe the first school-located influenza vaccination campaign with quadrivalent live-attenuated influenza vaccine (LAIV) among pre-school children in Italy, coupled with an innovative school-centred influenza-like illnesses (ILIs) surveillance using a self-sampling non-invasive saliva collection method. Methods The pilot study was proposed during the 2021/2022 influenza season to fifteen pre-schools in the Milan municipality. LAIV was offered directly in school to all healthy children without contraindications. ILI differential diagnosis was conducted by real-time RT-PCR for influenza A/B and SARS-CoV-2. Results Five pre-schools were involved in the pilot project and overall, 135 families (31.2%) participated in the study, adhering to both surveillance and vaccination; 59% of families had an immigrant background. No pupil experienced adverse reactions after vaccination. Nineteen saliva samples were collected from sixteen children (11.8%). Six samples (31.6%) tested positive for SARS-CoV-2; none was positive for influenza A/B. Conclusions The participation in the immunisation campaign was good, considering possible absences due to COVID-19 pandemic, and the intranasal administration was well tolerated and helped to overcome parental hesitancy. Saliva sampling represented a useful tool to reduce children’s stress and increase parents’ compliance. The high participation of families with an immigrant background suggests that school-based interventions can represent an effective strategy to overcome socioeconomic and cultural barriers

Additional file 1 of Serological investigation of SARS-CoV-2 infection in patients with suspect measles, 2017–2022

Supplementary Material