Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers.

BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).

A Systematic Review and Meta-Analysis on the Real-World Effectiveness of COVID-19 Vaccines against Infection, Symptomatic and Severe COVID-19 Disease Caused by the Omicron Variant (B.1.1.529).

Real-world data on the effectiveness of COVID-19 vaccines against the Omicron variant (B.1.1.529) is limited. This systematic review aimed to investigate the real-world effectiveness and durability of protection conferred by primary course and booster vaccines against confirmed Omicron infection, and severe outcomes. We systematically searched literature up to 1 August 2022. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled vaccine effectiveness (VE). Overall, 28 studies were included representing 11 million individuals. The pooled VE against Omicron infection was 20.4% (95%CI: 12.1-28.7%) and 23.4% (95%CI: 13.5-33.3%) against symptomatic infection with variation based on vaccine type and age groups. VE sharply declined from 28.1% (95%CI: 19.1-37.1%) at three months to 3.9% (95%CI: -24.8-32.7%) at six months. Similar trends were observed for symptomatic Omicron infection. A booster dose restored protection against Omicron infection up to 51.1% (95%CI: 43.8-58.3%) and 57.3% (95%CI: 54.0-60.5%) against symptomatic infection within three months; however, this waned to 32.8% (95%CI: 16.8-48.7%) within six months. VE against severe Omicron infection following the primary course was 63.6% (95%CI: 57.5-69.7%) at three months, decreased to 49% (95%CI: 35.7-63.4%) within six months, and increased to 86% after the first or second booster dose.

Impact of COVID-19 Containment Strategies and Meningococcal Conjugate ACWY Vaccination on Meningococcal Carriage in Adolescents.

OBJECTIVES: To examine if COVID-19 containment strategies were associated with reduced pharyngeal carriage of meningococci in adolescents. Also, to observe if carriage prevalence of meningococcal A, C, W and Y differed in meningococcal conjugate ACWY vaccinated and unvaccinated adolescents. DESIGN: Repeat cross-sectional study of pharyngeal carriage. SETTING: In 2020, recruitment commenced from February to March (pre-COVID-19) and recommenced from August to September (during COVID-19 measures) in South Australia. PARTICIPANTS: Eligible participants were between 17 and 25 years of age and completed secondary school in South Australia in 2019. RESULTS: A total of 1338 school leavers were enrolled in 2020, with a mean age of 18.6 years (standard deviation 0.6). Pharyngeal carriage of disease-associated meningococci was higher during the COVID-19 period compared with the pre-COVID-19 period (41/600 [6.83%] vs. 27/738 [3.66%]; adjusted odds ratio [aOR], 2.03; 95% CI: 1.22-3.39; P = 0.01). Nongroupable carriage decreased during COVID period (1.67% vs. 3.79%; aOR, 0.45; 95% CI: 0.22-0.95). Pharyngeal carriage of groups A, C, W and Y was similar among school leavers vaccinated with meningococcal conjugate ACWY (7/257 [2.72%]) compared with those unvaccinated (29/1081 [2.68%]; aOR, 0.86; 95% CI: 0.37-2.02; P = 0.73). Clonal complex 41/44 predominated in both periods. CONCLUSIONS: Meningococcal carriage prevalence was not impacted by public health strategies to reduce severe acute respiratory syndrome coronavirus 2 transmission and is unlikely to be the mechanism for lower meningococcal disease incidence. As international travel resumes and influenza recirculates, clinicians must remain vigilant for signs and symptoms of meningococcal disease. Vaccinating people at the highest risk of invasive meningococcal disease remains crucial despite containment strategies.

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents.

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.

Lessons for and from the COVID-19 pandemic response - An appraisal of guidance for the public health management of Invasive Meningococcal Disease.

BACKGROUND: COVID-19 has focussed public attention on the management of communicable disease like never before. Surveillance, contact tracing, and case management are recognised as key components of outbreak prevention. Development of guidance for COVID-19 has drawn from existing management of other communicable diseases, including Invasive Meningococcal Disease (IMD). IMD is a rare but severe outcome of Neisseria meningitidis infection that can be prevented through vaccination. Cases still occur sporadically, requiring ongoing surveillance and consistent management. To this end, national and international public health agencies have developed and published guidance for identification and management of IMD cases. AIM: To assess national and international guidelines for the public health management of IMD, with a focus on the recommendations for identification and management of "close contacts" to IMD cases. METHODS: Guidelines from six national and international public health agencies were assessed using a modified version of the Appraisal of Guidelines, Research and Evaluation (AGREE II) Instrument in four key domains: stakeholder involvement, developmental rigour, clarity, and applicability. A direct comparison of terminology and recommendations for identification and management of close contacts to IMD cases was also conducted. RESULTS: Guidelines from Europe and the United Kingdom rated most highly using the AGREE II Instrument, both presenting a clear, critical assessment of the strength of the available evidence, and the risks, costs, and benefits behind recommendations for management of close contacts. Direct comparison of guidelines identified inconsistencies in the language defining close contacts to IMD cases. CONCLUSION: Discrepancies between guidelines could be due to limited evidence concerning mechanisms behind disease transmission, along with the lack of a consistent process for development and review of guideline recommendations. COVID-19 management has demonstrated that international collaboration for development of public health guidance is possible, a practice that should be extended to management of other communicable diseases.

Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia.

Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases' surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.