Vaccination opportunities in multiple sclerosis patients treated with cladribine tablets

: The COVID-19 pandemic and the mass vaccination campaign highlighted the situation of the most vulnerable patients. In this work, we focused attention on patients who have Multiple Sclerosis (MS), particularly in treatment with cladribine tablets, trying to understand if and when it is possible to administer the vaccine successfully. Considering the innovative topic, we reviewed the existing literature with an analysis of the experiences also related to other vaccinations, including influenza and VZV, and very recent data from countries with vaccination campaigns already advanced. Overall, we have taken into account the mechanism of action, the pharmacokinetic/pharmacodynamic of cladribine and the changes in the immune system after its administration, together with the preliminary data about the humoral response to influenza, VZV and SARS-CoV-2 vaccinations in cladribine treated patients. In conclusion, data showed that the use of cladribine tablets seems to permit flexibility regarding vaccination timing and we suggest that vaccination in those patients should be safe and effective.

Regional Differences in COVID-19 Vaccine Hesitancy in December 2020: A Natural Experiment in the French Working-Age Population

It can be assumed that higher SARS-CoV-2 infection risk is associated with higher COVID-19 vaccination intentions, although evidence is scarce. In this large and representative survey of 6007 adults aged 18–64 years and residing in France, 8.1% (95% CI, 7.5–8.8) reported a prior SARS-CoV-2 infection in December 2020, with regional variations according to an East–West gradient (p < 0.0001). In participants without prior SARS-CoV-2 infection, COVID-19 vaccine hesitancy was substantial, including 41.3% (95% CI, 39.8–42.8) outright refusal of COVID-19 vaccination. Taking into account five characteristics of the first approved vaccines (efficacy, duration of immunity, safety, country of the vaccine manufacturer, and place of administration) as well as the initial setting of the mass vaccination campaign in France, COVID-19 vaccine acceptance would reach 43.6% (95% CI, 43.0–44.1) at best among working-age adults without prior SARS-CoV-2 infection. COVID-19 vaccine acceptance was primarily driven by vaccine characteristics, sociodemographic and attitudinal factors. Considering the region of residency as a proxy of the likelihood of getting infected, our study findings do not support the assumption that SARS-CoV-2 infection risk is associated with COVID-19 vaccine acceptance.

Reactogenicity of BNT162b2 mRNA COVID-19 Vaccine in a Young Working Age Population: A Survey among Medical School Residents, within a Mass Vaccination Campaign, in a Regional Reference Teaching Hospital in Italy

Vaccinations are a key prevention measure in fighting the COVID-19 pandemic. The BNT162b2 mRNA vaccine (BioNTech/Pfizer), the first to receive authorization, was widely used in the mass vaccination campaign in Italy. Healthcare workers were identified as a priority group for vaccination, but few studies have assessed its reactogenicity among the young working age population. An online survey was conducted to investigate the adverse reactions occurring in the 7 days following the first and second vaccination doses amongst resident doctors of the University of Genoa, employed at the IRCCS Ospedale Policlinico San Martino of Genoa, between 11 January and 16 March 2021. A total of 512 resident physicians were invited to participate in the study (female = 53.2%; mean age = 28.9 years), of whom 296 (female = 53.4%, mean age = 28.9 years) and 275 (female = 55.3%, mean age = 29.1 years) completed the survey after their first and second vaccination doses, respectively. In the 7 days following the first dose, most common adverse reactions were local pain (96.3%), fatigue (42.6%), headache (33.8%), arthromyalgia (28.0%), and 5.1% reported fever, while following the second dose, participants reported local pain (93.5%), fatigue (74.9%), headache (57.5%), arthromyalgia (58.2%), and fever (30.9%), with a higher prevalence among females. Systemic (but not local) reactions increased following the second vaccination, reaching severe intensity in 9.8% of participants and causing three or more events of moderate intensity in 23.7% of participants. Adverse reactions preventing regular daily activities could cause absenteeism among workers. These results can be useful to inform populations of young individuals, set expectations, and improve adherence to vaccination campaigns.

Can high SARS-CoV-2 adult vaccination rates help protect unvaccinated children? Evidence from a unique rapid mass vaccination campaign

Background: Mass vaccination has the potential to bring the COVID-19 pandemic to a halt by not only protecting individuals who have been vaccinated but also by providing cross-protection to unvaccinated individuals, such as children. However, this indirect protection effect from a vaccinated population onto an unvaccinated group is extremely difficult to observe in real-world situations. Methods: We studied cross-protection to unvaccinated individuals following an unprecedented rapid mass vaccination campaign in Europe. After a large outbreak of B.1.351 (Beta) in the district of Schwaz in Austria, the government offered every adult (16+) citizen of the district a vaccination with BNT162b2 between the 11th and 16th of March 2021. After this week, around 70% of the adult population of Schwaz had received their first dose, which made Schwaz the first widely inoculated region in Europe. The cohort of children under the age of 16 remained entirely unvaccinated (EMA only approved the vaccine for 12-15 year-olds on the 28th of May). This local mass vaccination campaign created a situation in which the vaccination coverage of the adult population sharply differed at the district border of Schwaz, while the coverage of those below the age of 16 remained the exact same. We compared SARS-CoV-2 cases among the adult population as well as children in Schwaz with case numbers of the same age cohorts from control regions. First, we compared Schwaz with a control group of other Austrian districts highly similar to Schwaz in many socio-demographic characteristics as well as in infection spread prior to the mass vaccination campaign. Second, we compared local populations residing along the border of Schwaz which live in the very same geographic area but with different vaccination coverage because they were not included in the vaccination campaign. Interpretation: Prior the mass vaccination campaign, we observed very similar infection spread across all age cohorts in Schwaz and the control regions. Around 3-4 weeks after the campaign, infections started to diverge between Schwaz and the control regions. While the difference was largest among the population aged 16–50 years (which was offered vaccination in the campaign), we also observed a statistically significant reduction in cases among the group of unvaccinated children. Our findings are robust to changes in the control group, as well as controls of a rich set of time and region specific effects. Policy implications: Our results constitute one of the first evidence of an indirect cross-protection effect from a group of vaccinated individuals to an unvaccinated group (in our case children). Given that in many countries the proposition to keep schools open during the academic year 2021/22 is a top priority, this evidence of community-protection is highly policy relevant.

BNT162b2 mRNA COVID-19 Vaccine Effectiveness in the Prevention of SARS-CoV-2 Infection and Symptomatic Disease in Five-Month Follow-Up: A Retrospective Cohort Study

To combat the COVID-19 pandemic, a mass vaccination campaign was initiated in Italy on 27 December 2020. The vaccine available to immunize Italian healthcare workers (HCWs) was the BNT162b2 mRNA COVID-19 vaccine (Comirnaty). This study evaluated the effectiveness of the vaccine against documented SARS-CoV-2 infection and symptomatic diseases in the medium- to long-term. HCWs at Bari Policlinico University-Hospital (Italy) who completed the vaccination schedule were matched with HCWs who had refused vaccination; the two groups were followed-up for 5 months (January–May 2021). Vaccine effectiveness (VE) against infection was 97.7% (95.4–99.0%) at 14–34 days after the first dose, and 94.8% (87.0–97.8%), 83.0% (65.0–92.0%), and 81.0% (42.0–94.0%) at 14–41, 42–69, and >69 days, respectively, after the second dose. The estimated VE for documented symptomatic disease was 99.2% (96.4–99.8%) at 14–34 days after the first dose and 97.2% (90.3–99.2%), 85.0% (63.0–94.2%), and 88.0% (42.0–97.6%) at 14–41, 42–69, and >69 days, respectively, after the second dose. Efforts to increase vaccination rates should be strengthened, including mandatory vaccination for HCWs and greater incentives to increase vaccine acceptance by the general population.

Waning immunity of the BNT162b2 vaccine: A nationwide study from Israel

ABSTRACTBackgroundStarting December 2020, Israel began a mass vaccination campaign against coronavirus administering the Pfizer BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no SARS-CoV-2 infections, a resurgent COVID-19 outbreak initiated mid June 2021. Possible reasons for the breakthrough were reduced vaccine effectiveness against the Delta variant, and waning immunity. The aim of this study was to quantify the extent of waning immunity using Israel’s national-database.MethodsData on all PCR positive test results between July 11-31, 2021 of Israeli residents who became fully vaccinated before June 2021 were used in this analysis. Infection rates and severe COVID-19 outcomes were compared between individuals who were vaccinated in different time periods using a Poisson regression, stratifying by age group and adjusting for possible confounding factors.ResultsThe rates of both documented SARS-CoV-2 infections and severe COVID-19 exhibit a statistically significant increase as time from second vaccine dose elapsed. Elderly individuals (60+) who received their second dose in March 2021 were 1.6 (CI: [1.3, 2]) times more protected against infection and 1.7 (CI: [1.0, 2.7]) times more protected against severe COVID-19 compared to those who received their second dose in January 2021. Similar results were found for different age groups.ConclusionsThese results indicate a strong effect of waning immunity in all age groups after six months. Quantifying the effect of waning immunity on vaccine effectiveness is critical for policy makers worldwide facing the dilemma of administering booster vaccinations.

Simulation of COVID-19 indoor emissions from coughing and breathing with air conditioning and mask protection effects

The COVID-19 infection has emerged as a disruptive pandemic at worldwide level. The study of the mechanism of contagion is one of the greatest challenges before a mass vaccination campaign that would protect populations. The study can support the development of knowledge and tools to develop possible strategies for containing its spread in future events. The saliva droplet aerosol expelled during breathing or coughing is the main cause for the propagation of the SARS-Cov-2. In this work, a URANS CFD approach was used to simulate the dispersion from the mouth of these particles in closed environments. The air conditioning system was considered. The conditions were varied to determine their impact on the diffusion of the aerosol. Lagrangian and Eulerian numerical approaches were used to model the coughing and the breathing events. These were validated with the puff theory, numerical and experimental results. A realistic case of a meeting room with two persons was simulated. Different characteristics of the expulsed aerosols and different ventilation system configurations were considered to demonstrate how these simulations can support management strategies for indoor occupation. Finally, the effect of the protective mask was introduced to quantify its beneficial effects to support safe indoor occupation.

A Modeling Study on Vaccination and Spread of SARS-CoV-2 Variants in Italy

From the end of 2020, different vaccines against COVID-19 have been approved, offering a glimmer of hope and relief worldwide. However, in late 2020, new cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started to re-surge, worsened by the emergence of highly infectious variants. To study this scenario, we extend the Susceptible-Exposed-Infectious-Removed model with lockdown measures used in our previous work with the inclusion of new lineages and mass vaccination campaign. We estimate model parameters using the Bayesian method Conditional Robust Calibration in two case studies: Italy and the Umbria region, the Italian region being worse affected by the emergence of variants. We then use the model to explore the dynamics of COVID-19, given different vaccination paces and a policy of gradual reopening. Our findings confirm the higher reproduction number of Umbria and the increase of transmission parameters due to the presence of new variants. The results illustrate the importance of preserving population-wide interventions, especially during the beginning of vaccination. Finally, under the hypothesis of waning immunity, the predictions show that a seasonal vaccination with a constant rate would probably be necessary to control the epidemic.