Absence of antibody responses to SARS-CoV-2 N protein in COVID-19 vaccine breakthrough cases.

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.

Reduced turnaround times through multi-sectoral community collaboration during the first surge of SARS-CoV-2 and associated effect on patient care and hospital operations.

BACKGROUND: In March 2020, an influx of admissions in COVID-19 positive patients threatened to overwhelm healthcare facilities in East Baton Rouge Parish, Louisiana. Exacerbating this problem was an overall shortage of diagnostic testing capability at that time, resulting in a delay in time-to-result return. An improvement in diagnostic testing availability and timeliness was necessary to improve the allocation of resources and ultimate throughput of patients. The management of a COVID-19 positive patient or patient under investigation requires infection control measures that can quickly consume personal protective equipment (PPE) stores and personnel available to treat these patients. Critical shortages of both PPE and personnel also negatively impact care in patients admitted with non-COVID-19 illnesses. METHODS: A multisectoral partnership of healthcare providers, facilities and academicians created a molecular diagnostic lab within an academic research facility dedicated to testing inpatients and healthcare personnel for SARS-CoV-2. The purpose of the laboratory was to provide a temporary solution to the East Baton Rouge Parish healthcare community until individual facilities were self-sustaining in testing capabilities. We describe the partnership and the impacts of this endeavor by developing a model derived from a combination of data sources, including electronic health records, hospital operations, and state and local resources. FINDINGS: Our model demonstrates two important principles: the impact of reduced turnaround times (TAT) on potential differences in inpatient population numbers for COVID-19 and savings in PPE attributed to the more rapid TAT.

Trichomonas vaginalis Brain Abscess in a Neonate.

We describe a case of cerebral trichomoniasis in a neonate in whom seizures and multiorgan failure developed during treatment for staphylococcal sepsis. Brain abscesses were identified with cranial sonography, and Trichomonas vaginalis was isolated from cerebrospinal fluid samples. The patient died despite metronidazole therapy.

Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive.

BACKGROUND: This study compared metabolic, hormonal and lipid profiles before and during use of a contraceptive vaginal ring (RING) releasing 15 mcg ethinyl estradiol (EE) and 120 mcg etonogestrel per day NuvaRing, Organon USA Inc., Roseland, NJ versus a low-dose oral contraceptive (PILL) containing 20 mcg EE and 100 mcg levonorgestrel daily (Aviane, Barr Pharmaceuticals Inc., Pomona, NY). STUDY DESIGN: Sixty-five women were randomized to either the RING or PILL treatment for five cycles. In the pretreatment cycle (Cycle Days 2-5) and during Weeks 2 and 3 of the fifth treatment cycle, a 75-g oral glucose tolerance test (OGTT) was performed. Baseline samples were used to evaluate basal hormonal, metabolic and lipid levels. RESULTS: Forty-two women completed the study. Basal insulin resistance (HOMA-IR) was slightly decreased, whereas a significant reduction in the insulin sensitivity index (IS(OGTT)) was found in women on PILL therapy compared to those in the RING group (p<.035). Pancreatic beta-cell function was not significantly altered with either treatment. CONCLUSION: The lower-dose, nonoral hormonal RING had a lesser impact on carbohydrate metabolism and greater reduction of free androgen and dehydroepiandrosterone sulfate levels than PILL treatment.

Interrelationships of serum estradiol, estrone, and estrone sulfate, adiposity, biochemical bone markers, and leptin in post-menopausal women.

OBJECTIVE: The aim of this study was to examine the relationships between endogenous estrogens and adiposity, bone markers, and leptin in post-menopausal (PM) women. DESIGN: Seventy-three post-menopausal (PM) women participated in a clinical correlational study. Weight, height, waist-hip ratio, fasted morning serum and first morning voided urine samples were obtained to compare body mass index (BMI), waist-hip ratio, endogenous estrogens, leptin, and bone markers. Serum estradiol, estrone (E1), estrone sulfate (E1S), leptin, osteocalcin, and urinary deoxypyridinoline (Dpd) were determined. RESULTS: Significant positive relationships were found between BMI and estradiol, E1, and E1S (r = 0.52, 0.38, and 0.29; P < or = 0.001, 0.001, and 0.013 respectively). Significant relationships between leptin and estrogens were revealed, but were not significant when BMI was used as a covariate. Although many subjects revealed elevated bone marker levels, no correlation between estrogens or BMI and bone markers (Dpd and osteocalcin) was found. CONCLUSIONS: There are significant positive correlations between estrogens and BMI in PM women. Increasing levels of estradiol, E1, and E1S with increasing BMI may be an indicator of adiposity, but are without effect as a stimulatory factor on leptin production. Waist-hip ratio did not significantly affect leptin concentrations when accounting for BMI. Due to assay sensitivity in the present study, data represent a more precise representation of these relationships. The lack of correlation between estrogens and bone marker levels may have been due to low estrogen levels in PM women.

Variability of serum estrogens among postmenopausal women treated with the same transdermal estrogen therapy and the effect on androgens and sex hormone binding globulin.

OBJECTIVE: To examine the variability of serum estrogens in response to transdermal estrogen replacement therapy (ET), and to determine the effects on androgens and sex hormone binding globulin (SHBG). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Women's hospital. PATIENT(S): Two groups of postmenopausal women: [1] 21 women not on ET enrolled and 17 completed the study; [2] 19 women on continuous transdermal ET enrolled and 13 completed the study. INTERVENTION(S): Women not on ET were administered a placebo patch or a newly initiated estrogen patch, then crossed over to the alternate treatment. Serum samples were obtained at baseline and the subsequent 3 days from the placebo and new-patch groups and from a separate group of women receiving continuous estrogen patch treatment. MAIN OUTCOME MEASURE(S): Estradiol (E(2)), estrone, estrone sulfate, T, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, free androgen index, and SHBG. RESULT(S): There was considerable intrapatient and interpatient variability in the estrogen response to identical treatment doses, with E(2) values differing between women as much as 138 pg/mL and E(2) increases above baseline differing as much as 90 pg/mL. Continuous treatment increased SHBG and decreased androstenedione levels; however, levels of T, DHEA, DHEAS, and free androgen index did not change. CONCLUSION(S): There is great variability of estrogen in response to transdermal ET, but minimal effect on circulating androgens.