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Understanding the risk factors for breakthrough coronavirus disease 2019 (COVID-19) (BC19) is critical to inform policy. Herein, we assessed Delta (Lineage B.1.617.2) variant-specific effectiveness of the BNT162b2 (Pfizer) vaccine and characterized Delta-driven BC19 cases (fully vaccinated individuals who get infected) with known-time-since-vaccination. In this longitudinal prospective study (January 21–October 30, 2021), 90 naïve and 15 convalescent individuals were enrolled at the initiation of vaccination. Samples from 27 unvaccinated individuals with previous laboratory-confirmed COVID-19 diagnosis were collected at a single time point. Longitudinal serology profile (antibodies against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] S and N proteins) and live-virus-based neutralization capacities were assessed while controlling for age. Sex, age, history of reactions to the COVID-19 vaccine, and viral neutralization capacities were identified as significant risk factors for breakthrough COVID-19. At 8 months postvaccination, male sex, individuals ⩾65 years of age, and individuals who experienced noticeable side effects with the COVID-19 vaccine were at 5.47 ( p-value = 0.0102), 4.33 ( p-value = 0.0236), and 4.95 ( p-value = 0.0159) fold greater risk of BC19 as compared to their peers, respectively. Importantly, every five-fold increase in viral neutralization capacities (by live-virus-based assays) was significantly associated with ~4-fold reduction in the risk occurrence of breakthrough COVID-19 ( p-value = 0.045). Vaccine boosting remarkably increased these viral neutralization capacities by 16.22-fold ( p- value = 0.0005), supporting the importance of the BNT162b2 booster in efforts to control the incursion of future variants into the population at large. Strikingly, BC19 cases exhibited a delayed/absent antibody response to the N protein, suggesting limited exposure to the virus. Since antibodies against N protein are widely used to evaluate the extent of virus spread in communities, our finding has important implications on the utility of existing serological diagnostic and surveillance for COVID-19.

Background: Long-term control of SARS-CoV-2 via vaccination has been confounded by the introduction of the Delta variant (B1.617.2). Herein, we assessed Delta variant-specific effectiveness of BNT162b2 and characterize Delta-driven breakthrough COVID-19 cases with known-time-since-vaccination. Methods: In this longitudinal, prospective study (January 21 to September 01 2021), we obtained samples from naive and convalescent individuals including those vaccinated with BNT162b2 to evaluate the implications of the Delta variant. Serology profile (antibodies against S and N protein) and live-virus based neutralization capacities against the B.1 lineage virus and the Delta variant were assessed, while controlling for age. Findings: 99 eligible participants including 85 naive and 14 convalescent individuals at the initiation of vaccination, were enrolled. In naive vaccinated individuals, neutralizing capacity against a clinical isolate of the SARS-CoV-2 Delta variant was reduced 4.85-fold compared to the basal B.1 lineage. Further, individuals ≥60 years of age (yoa) have significantly lower neutralization capacities against the Delta variant than younger vaccinated individuals (

Objective We prospectively evaluated differences in fasting- and oral glucose tolerance test (OGTT)-derived indices of insulin action in Caucasian (Cau) and African-American (AA) pregnant women and compared them with obstetric outcomes. Study design IRB-approved prospective study in 171 pregnant women undergoing a 3-h OGTT. Mathematical modeling was used to evaluate insulin response, insulin activity and glucose tolerance in fasting and postglucose ingestion state. Insulin sensitivity indices derived from fasting (HOMA-IR) and glucose-stimulated values (SIOGTT) were compared. An insulin sensitivity-secretion index (IS-SI) was calculated from the product of the SIOGTT and early-phase insulin secretion. Results Forty-nine patients had gestational diabetes (GDM), 28 had gestational impaired glucose tolerance (GIGT) and 94 had normal glucose tolerance after an abnormal glucose challenge test (NGT-abnGCT). Insulin sensitivity was lowest in women with GDM. In all groups, pregnant AA women were significantly more insulin resistant than Cau women, based on both HOMA-IR and SIOGTT, but had enhanced insulin secretion compared to their Cau counterparts. The mean IS-SI progressively improved for all women from GDM to GIGT to NGT-abnGCT. Women with NGT-abnGCT had a higher prevalence of large-for-gestational age (LGA) newborns and significantly higher cesarean section rate. Discussion Insulin measures along with glucose determinations during OGTT testing in pregnant women at risk for diabetes provide valuable information that varies according to race. We observed that pregnant women with a lesser degree of glucose tolerance abnormality during pregnancy who receive no intervention have a higher risk for LGA infants and significantly increased C-section rate (ClinicalTrials.gov number, NCT006874791).