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SUMMARYBCG vaccination induces heterologous protection against respiratory tract infections, and in children improves survival independently of tuberculosis prevention. The phase III ACTIVATE-2 study assessed whether BCG could also protect against COVID19 in the elderly. In this double-blind, randomized trial, elderly Greek patients were randomized (1:1) to receive either BCG revaccination or placebo at hospital discharge, followed by 6 months observation for incidence of COVID19 infection. BCG revaccination resulted in 68% risk reduction for total COVID19 clinical and microbiological diagnoses (OR 0.32, 95% CI 0.13-0.79). Five patients in the placebo group and one in the BCG-vaccinated group had severe COVID19 that necessitated hospitalization. 3 months after BCG vaccination 1.3% of placebo and 4.7% of BCG-vaccinated volunteers had anti-SARS-CoV-2 antibodies. These data argue that BCG revaccination is safe and protects the elderly against COVID19. BCG revaccination may represent a viable preventive measure against COVID19.

Background Type I Diabetes mellitus (DT1) is a multifactorial disease with various genetic and environmental factors involved in its pathophysiology. Several nutritional factors such as the timing of exposure to solid foods may increase the risk of DT1. The aim of this systematic review was to investigate the association between the time of introducing solid food into infant's nutrition during the first year of life and the risk of developing DT1. Methods PubMed and Science Direct were searched from inception to October 2019 for observational studies that investigated the above association. No restrictions on language or publication date were applied. Specific inclusion and exclusion criteria were set for the selection of articles. Title and abstract screening were performed by two independent researchers and data were extracted from shortlisted articles. Results In total, 76 studies were screened, and 7 articles met the inclusion criteria. The analysis shows that early exposure (before or during 3 or 4 months) and subsequent exposure (during or after 6 or 7 months) was associated with an increased risk of developing DT1 and/or pancreatic islet autoimmunity, compared to an intermediate exposure period (4-6 months, 4-5 months or 3-6 months). Conclusions The evidence suggests that an interim exposure period of genetically predisposed infants to DT1 from 4 to 5 months of age may reduce the risk of developing DT1 in later life as compared to early or later exposure. However, due to the limitations of the studies, further investigation is required to inform DT1 prevention practices. Key messages There is some evidence indicating that early exposure and later exposure to solid food may increase the risk of developing DT1 in children with a genetic predisposition. Due to the methodological heterogeneity across the studies included, more reliable data from large prospective studies and randomized clinical trials are needed.

BCG vaccination in children protects against heterologous infections and improves survival independently of tuberculosis prevention. The phase III ACTIVATE trial assessed whether BCG has similar effects in the elderly. In this double-blind, randomized trial, elderly patients (n = 198) received BCG or placebo vaccine at hospital discharge and were followed for 12 months for new infections. At interim analysis, BCG vaccination significantly increased the time to first infection (median 16 weeks compared to 11 weeks after placebo). The incidence of new infections was 42.3% (95% CIs 31.9%–53.4%) after placebo vaccination and 25.0% (95% CIs 16.4%–36.1%) after BCG vaccination; most of the protection was against respiratory tract infections of probable viral origin (hazard ratio 0.21, p = 0.013). No difference in the frequency of adverse effects was found. Data show that BCG vaccination is safe and can protect the elderly against infections. Larger studies are needed to assess protection against respiratory infections, including COVID-19 (ClinicalTrials.gov NCT03296423)., Graphical Abstract, Highlights • ACTIVATE is a prospective randomized trial of BCG vaccination in the elderly • BCG increased the time to first infection and decreased the incidence of new infection • Strongest protection was found against viral respiratory tract infections • Epigenetic reprogramming and increased cytokine production was found in monocytes, Interim analysis of the phase III ACTIVATE trial to evaluate protection against infection in elderly patients reveals that BCG vaccination is safe, increases the time to first infection, and shows protection against viral respiratory infections.