Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE).

The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy delivery were not available. We aimed to evaluate potential factors influencing the outcome of the COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing the COVID-19 vaccination with gastro-entero-pancreatic and neuroendocrine neoplasms, treated at our institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection, 86.9% had received two-doses of Pfizer-BioNTech and the rest had received the Moderna vaccine. All patients obtained a subsequent immune-response. Chemotherapy seems to determinate a significantly lower antibody response after vaccination compared to the other anti-cancer agents (p = 0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs. >7 days from the last systemic treatment (p = 0.77) and lymphocytes count (p = 0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue, but rather that the quality of the subset of lymphocytes before the vaccination determine the efficacy level of immune-response in this population.

European Cohorts of patients and schools to Advance Response to Epidemics (EuCARE): a cluster randomised interventional and observational study protocol to investigate the relationship between schools and SARS-CoV-2 infection.

BACKGROUND: Contradictory results were reported on the role of school closure/reopening on the overall SARS-CoV-2 transmission rate, as well as on which kind and level of mitigation measures implemented in schools may be effective in limiting its diffusion. Some recent studies were reassuring, showing that opening did not increase the community spread, although teachers and families are worried about the high class density. On the other hand, distance learning was associated with a negative impact on learning, sociability and psychological health, especially in vulnerable children. As it becomes clear that the SARS-CoV-2 pandemic will last for a long time, there is a high need for studies and solutions to support safe schools opening based on scientific evidence of harms and benefits. The Lolli-Methode (LM) is a strategy for epidemiological surveillance and early intervention aiming at SARS-CoV-2 outbreaks' reduction in schools, relying on polymerase chain reaction analysis of saliva samples. METHODS: In this cluster randomised trial protocol, we aim to determine whether the LM is useful to support schools opening and to reduce clusters and attack rates in schools, compared with the standard of care (SoC) surveillance by public health departments. This multicenter study will enrol 440 classes (around 8800 students, teachers and other personnel) from two countries, cluster randomised to LM or SoC. The samples from the pools will be collected and tested using PCR-based techniques. Test results will be combined with questionnaires filled in by children, parents, schoolteachers, and principals, concerning ongoing mitigation measures, their perceived psychological impact and other health and socio-economic information. An ancillary observational study will be carried out to study the prevalence of SARS-CoV-2 in schools, frequencies and size of clusters and attack rates, to compare the effectiveness of the different preventive measures adopted and to evaluate psychological issues in students and teachers in relation to the pandemic's containment measures. DISCUSSION: By the end of this study, we will have defined and characterised the applicability of the LM for SARS-CoV-2 surveillance, as well as the impact of pandemic preventive measures on children and teachers. Trial registration International Standard Randomised Controlled Trial Number: NCT05396040, 27.05.2022.

Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis.

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

SARS-CoV-2 Circulation in the School Setting: A Systematic Review and Meta-Analysis.

The contribution of children to viral spread in schools is still debated. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Literature searches on 15 May 2021 yielded a total of 1088 publications, including screening, contact tracing, and seroprevalence studies. MOOSE guidelines were followed, and data were analyzed using random-effects models. From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% confidence interval (CI) 0.05-0.81) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%, 95% CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (odds ratio (OR) 0.26, 95% CI 0.11-0.63) and less susceptible to infection (OR 0.60; 95% CI 0.25-1.47). Lastly, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children were 43% significantly less likely than adults to test positive for antibodies (OR 0.57, 95% CI 0.49-0.68). These findings may not applied to the Omicron phase, we further planned a randomized controlled trial to verify these results.

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment.

PURPOSE: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment. PATIENTS AND METHODS: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose. RESULTS: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 109/L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009). CONCLUSION: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 109/L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS. GOV IDENTIFIER: NCT04932863.