Asymptomatic SARS-CoV-2 Infection by Age: A Global Systematic Review and Meta-analysis.

BACKGROUND: Asymptomatic SARS-CoV-2 infections have raised concerns for public health policies to manage epidemics. This systematic review and meta-analysis aimed to estimate the age-specific proportion of asymptomatic SARS-CoV-2 infected persons globally by year of age. METHODS: We searched PubMed, Embase, medRxiv and Google Scholar on September 10, 2020, and March 1, 2021. We included studies conducted during January to December 2020, before routine vaccination against COVID-19. Because we expected the relationship between the asymptomatic proportion and age to be nonlinear, multilevel mixed-effects logistic regression (QR decomposition) with a restricted cubic spline was used to model asymptomatic proportions as a function of age. RESULTS: A total of 38 studies were included in the meta-analysis. In total, 6556 of 14,850 cases were reported as asymptomatic. The overall estimate of the proportion of people who became infected with SARS-CoV-2 and remained asymptomatic throughout infection was 44.1% (6556/14,850, 95% CI: 43.3%-45.0%). The predicted asymptomatic proportion peaked in children (36.2%, 95% CI: 26.0%-46.5%) at 13.5 years, gradually decreased by age and was lowest at 90.5 years of age (8.1%, 95% CI: 3.4%-12.7%). CONCLUSIONS: Given the high rates of asymptomatic carriage in adolescents and young adults and their active role in virus transmission in the community, heightened vigilance and public health strategies are needed among these individuals to prevent disease transmission.

Early-Life Antibiotic-Driven Dysbiosis Leads to Dysregulated Vaccine Immune Responses in Mice.

Antibody-mediated responses play a critical role in vaccine-mediated immunity. However, for reasons that are poorly understood, these responses are highly variable between individuals. Using a mouse model, we report that antibiotic-driven intestinal dysbiosis, specifically in early life, leads to significantly impaired antibody responses to five different adjuvanted and live vaccines. Restoration of the commensal microbiota following antibiotic exposure rescues these impaired responses. In contrast, antibiotic-treated adult mice do not exhibit impaired antibody responses to vaccination. Interestingly, in contrast to impaired antibody responses, immunized mice exposed to early-life antibiotics display significantly enhanced T cell cytokine recall responses upon ex vivo restimulation with the vaccine antigen. Our results demonstrate that, in mice, antibiotic-driven dysregulation of the gut microbiota in early life can modulate immune responses to vaccines that are routinely administered to infants worldwide.

Randomized trial using ultrasound to assess intramuscular vaccination at a 60° or 90° needle angle.

OBJECTIVE: Globally, recommendations differ on the ideal angle of needle insertion to ensure vaccinate deposition in muscle for optimal safety and immunogenicity. This study aimed to compare the level of vaccinate deposition during vaccination, using two different needle angles (60° and 90°), in young children, adolescents and adults. METHODS: In this randomized cross-over study, two doses of a licensed hepatitis vaccine, were administered to study participants, at a 60° or 90° angle using a fixed template. Ultrasonography was performed with a Philips iu22 ultrasound system. Real time clips and hard copies of images were recorded showing the injection and level of deposition of the vaccinate. Reactogenicity at the site of administration was assessed by participants/parents. RESULTS: Nineteen participants were enrolled including children, adolescents and adults. Of the total 38 injections performed, 29 (76%) were confirmed by ultrasound as intramuscular (IM), 3 (8%) as not IM, and 6 (16%) unknown. For vaccinations visualised and administered at 60°, 87% (13/15) were intramuscular vs 94.1% (16/17) for those administered at 90°. A body mass index (BMI)≤25 was associated with a higher likelihood of IM injection compared to BMI>25 (p=0.038). There were no differences in reactogenicity for either 60° or 90° angle of administration. CONCLUSION: For the majority of vaccinees, a 60-90° angle of vaccine administration is appropriate for IM deposition of vaccinate. The likelihood of intramuscular deposition is reduced for individuals with a BMI>25. The increasing rates of obesity globally highlight the importance of tailoring vaccination procedures accordingly.

Ultrasound examination of extensive limb swelling reactions after diphtheria-tetanus-acellular pertussis or reduced-antigen content diphtheria-tetanus-acellular pertussis immunization in preschool-aged children.

OBJECTIVE: The aim of this study was to determine the site, extent, and resolution of tissue involvement when extensive limb swelling occurred in the injected limb for children who received diphtheria-tetanus-acellular pertussis or reduced-antigen content diphtheria-tetanus-acellular pertussis vaccine at 4 to 6 years of age. METHODS: Children who had experienced an injection site reaction at 18 months of age were assigned randomly to receive an intramuscular injection of either reduced-antigen content diphtheria-tetanus-acellular pertussis vaccine or diphtheria-tetanus-acellular pertussis vaccine between 4 and 6 years of age. Children who developed extensive limb swelling were recruited for assessment by clinical examination; ultrasound studies of the affected and opposite (control) arms were performed 24 to 48 hours after immunization and 48 to 96 hours later. RESULTS: Twelve children with extensive limb swelling were enrolled in the study. Ultrasound examinations demonstrated swelling of both the subcutaneous and muscle layers of the vaccinated arm. Ultrasound assessment showed that the swelling exceeded the clinical measurements of skin redness and swelling. Subcutaneous and muscle tissues expanded to 281% and 111% of the tissue thicknesses of the control arm, respectively. Repeat ultrasound examinations after 48 to 96 hours showed considerable resolution of muscle swelling, compared with subcutaneous tissue swelling. There was no significant difference in the extent of swelling detected between children who received diphtheria-tetanus-acellular pertussis vaccine and those who received reduced-antigen content diphtheria-tetanus-acellular pertussis vaccine. CONCLUSION: Extensive limb swelling reactions after diphtheria-tetanus-acellular pertussis or reduced-antigen content booster immunizations involved swelling of subcutaneous and muscle tissues with swelling and duration more marked in subcutaneous tissue.