ABSTRACT
High priority efforts are under way to support the development of novel mucosal COVID-19 vaccines, such as the US Governments Project NextGen and the Center for Epidemic Preparedness Innovations (CEPI) goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how the immunogenicity of mucosal vaccines will be evaluated. This study investigated the role of oral mucosal antibody responses in viral clearance and in COVID-19 symptom duration. Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022. High and moderate oral fluid anti-spike (S) SIgA post infection was associated with significantly higher likelihood of viral clearance and of COVID-19 symptom resolution across age groups. Those with high and moderate anti-S SIgA cleared the virus and recovered 14 days (95% CI: 10-18 days) and 9-10 days (95% CI: 6-14 days) earlier, respectively. Delayed but higher oral fluid anti-S IgG was associated with significantly longer time to viral clearance and recovery. The effect size of moderate or high SIgA was equivalent to prior COVID-19 vaccine immunity, which was also associated with faster clearance and recovery. Unvaccinated adults with prolonged COVID-19 symptoms had significantly lower anti-RBD SIgA 15-30 days after infection onset (p<0.001). Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new vaccines that can boost local mucosal immunity. DisclaimerThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Subject(s)
COVID-19ABSTRACT
Background Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding safety of these vaccines for the pregnant persons and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, efficacy or effectiveness, reactogenicity, and immunogenicity of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review (LSR) of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide information necessary to help guide vaccine policy decisions.Methods We aim to conduct a LSR based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety (i.e., impacts on obstetric and neonatal outcomes), efficacy or effectiveness of COVID-19 vaccines in pregnant persons. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including pre-specified subgroup and sensitivity analyses, and will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to evaluate the certainty of evidence.Conclusion This will be the first living systematic review (LSR) and meta-analysis assessing the safety, reactogenicity, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons. An online interactive dashboard for data visualization using Microsoft Power BI will be developed to regularly update and disseminate the latest findings (an in-progress version is available at https://safeinpregnancy.org/lsr/). In addition, the findings will be disseminated through publications and presentations.
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children. We compared Receptor Binding Domain binding antibody (RBDAb) and SARS-CoV-2 neutralizing antibody (neutAb) in children aged 0-4 years, 5-17 years, and in adults aged 18-62 years in a SARS-CoV-2 household study. Among 55 participants seropositive at enrollment, children aged 0-4 years had >10-fold higher RBDAb titers than adults (373 vs.35, P<0.0001), and the highest RBDAb titers in 11/12 households with seropositive children and adults. Children aged 0-4 years had 2-fold higher neutAb than adults, resulting in higher binding to neutralizing (B/N)Ab ratios compared to adults (1.9 vs. 0.4 for ID50, P=0.0002). Findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutAb to measure the immunogenicity of COVID-19 vaccines in children aged 0-4 years.