Importance Maternal immunization with tetanus toxoid and reduced diphtheria toxoid acellular pertussis (Tdap) vaccine could prevent infant pertussis. The effect of vaccine-induced maternal antibodies on infant responses to diphtheria and tetanus toxoids acellular pertussis (DTaP) immunization is unknown. Objective To evaluate the safety and immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to DTaP. Design, Setting and Participants Phase I, randomized, double-masked, placebo-controlled clinical trial conducted in private (Houston) and academic (Durham, Seattle) obstetric practices from 2008 to 2012. Forty eight healthy 18–45 year-old pregnant women received Tdap (n=33) or placebo (n=15) at 30–32 weeks’ gestation with cross-over Tdap immunization postpartum. Interventions Tdap vaccination at 30–32 weeks’ gestation or post-partum. Outcome Measures Primary: Maternal and infant adverse events, pertussis illness and infant growth and development (Bayley-III screening test) until 13 months of age. Secondary: Antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months postpartum, and in infants at birth, 2 months, and after the third (7 months) and fourth (13 months) doses of DTaP. Results All participants delivered healthy newborns. No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 78.8% (95% CI: 61.1%, 91.0%) and 80% (CI: 51.9%, 95.7%) pregnant and postpartum women, respectively. Injection site pain was the predominant symptom. Systemic symptoms were reported in 36.4% (CI: 20.4%, 54.9%) and 73.3% (CI: 44.9%, 92.2%) pregnant and postpartum women, respectively. Malaise and myalgia were most common. Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in women who received Tdap during pregnancy and in their infants at birth and at age 2 months when compared to infants of women immunized postpartum. Antibody responses in infants of Tdap recipients during pregnancy were modestly lower after 3 DTaP doses, but not different following the fourth dose. Conclusions and Relevance This preliminary safety assessment did not find an increased risk of adverse events among women who received Tdap vaccine at 30–32 weeks’ gestation or their infants. Maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap vaccination during pregnancy. Trial Registration ClinicalTrials.gov, study identifier: NCT00707148. URL: http://www.clinicaltrials.gov

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Background During the COVID-19 pandemic, a minority of index cases are associated with a majority of secondary cases suggesting that super-spreaders could drive the pandemic. We identified a phenotype in individuals with extremely high viral load who could act as super-spreaders. Methods Data were analyzed from individuals tested for SARS-CoV-2 from March 18 through August 15, 2020. Outcomes were compared using contingency table and quantile regression to test the equality of medians between the pandemic waves and by viral load groups. Results Of the 11,564 samples tested, 1,319 (11.4%) were positive for SARS-CoV-2. An increase in weekly median viral load occurred in the second wave of the SARS-CoV2 pandemic. This population was more likely to be women, outpatients, symptomatic and have an extremely high or high viral load. In patients with multiple RT-PCR positive tests, the duration of viral shedding was comparable between individuals with asymptomatic/mild and mild/moderate illness severity. Conclusions We detected a small group of individuals with extremely high SARS-CoV-2 viral load with mild illness. We believe that these individuals’ characteristics could be consistent with the super-spreader phenomenon and that greater awareness of the social dynamics of these individuals is needed to understand the spread of SARS-CoV-2.

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In over one third of ARI cases, participants had symptoms consistent with ALRTI. Infection with HRV, RSV, or influenza virus was commonly detected in patients with ALRTI. Viral ALRTI during pregnancy appears to be common and is associated with significant morbidity.

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a b s t r a c tObjective: To describe the clinical presentation and laboratory diagnosis of pregnant women with respiratory syncytial virus (RSV) infection. Methods: Pregnant women in their second and third trimester were enrolled during the course of routine prenatal care visits when they were asymptomatic within the preceding two weeks (healthy controls) or when they reported symptoms of acute respiratory illness (ARI) of 7 days of duration (cases). Clinical outcomes were assessed at enrollment and two weeks after. Re-enrollment was allowed. Nasalpharyngeal secretions were evaluated for respiratory pathogens by real-time reverse transcription polymerase chain reaction (PCR). Sera were tested for RSV-specific antibody responses by Western Blot, microneutralization assay, and palivizumab competitive antibody assay. Results: During the 2015-2016 respiratory virus season, 7 of 65 (11%) pregnant women with ARI at their initial enrollment and 8 of 77 (10%) pregnant women with ARI during the study period (initial or reenrollment) had PCR-confirmed RSV infection. Four (50%) PCR-confirmed RSV ARI cases reported symptoms of a lower respiratory tract illness (LRTI), one was hospitalized. Combining PCR and serology data, the RSV attack rate at initial enrollment was 12% (8 of 65), and 13% (10 of 77) based on ARI episodes. Among healthy controls, 28 of 88 (32%) had a Western Blot profile suggestive of a recent RSV infection either in the prior and/or current season. Conclusion: RSV had an attack rate of 10-13% among ambulatory pregnant women receiving routine prenatal care during the respiratory virus season. The serology results of healthy controls suggest a potentially higher attack rate. Future studies should be aware of the combined diagnostic strength of PCR and serology to identify RSV infection. As maternal RSV vaccine candidates are evaluated to protect young infants, additional priority should be placed on outcomes of pregnant women.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China, and then rapidly spread causing an unprecedented pandemic. A robust serological assay is needed to evaluate vaccine candidates and better understand the epidemiology of coronavirus disease (COVID-19).MethodsWe used the full-length spike (S) protein of SARS-CoV-2 for the development of qualitative and quantitative IgG and IgA anti-S enzyme linked immunosorbent assays (ELISA). A total of 320 sera used for assay development were comprised of pandemic sera from SARS-CoV-2 infected adults (n=51) and pre-pandemic sera (n=269) including sera from endemic human coronavirus infected adults. Reverse cumulative curves and diagnostic test statistics were evaluated to define the optimal serum dilution and OD cutoff value for IgG anti-S and IgA anti-S ELISAs. The IgG and IgA anti-S, and three functional antibodies (ACE-2 receptor blocking antibody, lentipseudovirus-S neutralizing antibody, and SARS-CoV-2 neutralizing antibody) were measured using additional SARS-CoV-2 PCR positive sera (n=76) and surveillance sera (n=25). Lastly, the IgG and IgA anti-S levels were compared in different demographic groups.ResultsThe optimal serum dilution for the qualitative IgG anti-S ELISA was at 1:1024 yielding a 99.6% specificity, 92.2% sensitivity, 92.9% positive predictive value (PPV), and 99.6% negative predictive value (NPV) at a SARS-CoV-2 seroprevalence of 5%. The optimal serum dilution for the qualitative IgA anti-S ELISA was at 1:128 yielding a 98.9% specificity, 76.5% sensitivity, 78.3% PPV, and 98.8% NPV at the same seroprevalence. Significant correlations were demonstrated between the IgG and IgA (r=0.833 for concentrations, r=0.840 for titers) as well as between IgG and three functional antibodies (r=0.811-0.924 for concentrations, r=0.795-0.917 for titers). The IgG and IgA anti-S levels were significantly higher in males than females (p<0.05), and in adults with moderate/severe symptoms than in adults with mild/moderate symptoms (p<0.001).ConclusionWe developed a highly specific and sensitive IgG anti-S ELISA assay to SARS-CoV-2 using full length S protein. The IgG anti-S antibody level was strongly associated with IgA and functional antibody levels in adults with SARS-CoV-2 infection. Gender and disease severity, rather than age, play an important role in antibody levels.