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Purified 111Ag was used as a radiotracer to investigate silver loading and release, pharmacokinetics and biodistribution of polyphosphoester-based degradable shell crosslinked knedel-like (SCK) nanoparticles as a comparison to the previously reported small molecule, N-heterocyclic silver carbene complex analogue (SCC1) for the delivery of therapeutic silver ions in mouse models. Biodistribution studies were conducted by aerosol administration of 111Ag acetate, [111Ag]SCC1 and [111Ag]SCK doses directly into the lungs of C57BL/6 mice. Nebulization of the 111Ag antimicrobials resulted in an average uptake of 1.07 ± 0.12% of the total aerosolized dose given per mouse. The average dose taken into the lungs of mice was estimated to be 2.6 ± 0.3% of the dose inhaled per mouse for [111Ag]SCC1 and twice as much dose was observed for the [111Ag]SCKs (5.0 ± 0.3% and 5.9 ± 0.8% for [111Ag]aSCK and [111Ag]zSCK, respectively) at 1 h post administration (p.a.). [111Ag]SCKs also exhibited higher dose retention in the lungs; 62 – 68% for [111Ag]SCKs and 43% for [111Ag]SCC1 of the initial 1 h dose was observed in the lungs at 24 h post administration (p.a.). This study demonstrates the utility of 111Ag as a useful tool for monitoring the pharmacokinetics of silver loaded antimicrobials in vivo.
Background SARS-CoV-2 infections during pregnancy continue in this ongoing pandemic. Care of mother-infant dyads affected by SARS-CoV-2 infection in pregnancy has evolved. Perinatal viral transmission is rare. However, there remain few detailed reports on characteristics and management of these infants during neonatal hospitalization. Our objective was to investigate management and outcomes of infants born to women with laboratory-confirmed SARS-CoV-2 infection in pregnancy including resuscitation, NICU care, separation, and breastfeeding. Methods This is a study of mother-infant dyads with SARS-CoV-2 in pregnancy at Prentice Women’s Hospital in Chicago, IL (3/2020-11/2020). Dyads were tracked prospectively with data obtained by review of electronic medical records including demographics, maternal clinical history, COVID symptoms, and neonatal course. Women were universally screened with SARS-CoV-2 PCR at admission. Mothers were categorized as 1) acute infection (-14–0 days from delivery) vs. previous infection (>14 days), and 2) symptomatic vs. asymptomatic (defined by CDC criteria). Infants of mothers with acute infection were tested for SARS-CoV-2. Results We report a diverse cohort of 210 women with SARS-CoV-2 in pregnancy, 114 acute and 96 previous infection (range 0–229 days between positive PCR and delivery) [Table 1]. Over half (56%) of women were symptomatic, 29/114 (25%) with acute infection, 89/96 (93%) with previous infection. Of 211 infants, one asymptomatic infant tested positive for SARS-CoV-2. The overall rate of preterm birth was 10.9% in this cohort. The rate of preterm birth was 26.6% (8/30) in the symptomatic acute infection group (p=0.055) and birthweight was significantly lower (p=0.03). There was no apparent increased need for resuscitation at delivery. APGARs were 8 (8–9) and 9 (8–9) at 1 and 5 minutes, respectively. Six percent of infants >35 weeks had respiratory distress. About 7% had failed hearing screen (historic Prentice rate ~4%). Separation of infants from mothers with acute infection decreased over time due to policy changes based on available safety data for rooming in (Cuzick’s test for trend p<0.001). Most infants (75%) received breastmilk in the hospital over this timeframe; this was low initially and increased over this timeframe (p<0.001). For example, 45% of mothers with acute infection provided breastmilk in May compared to nearly 100% in November. Twelve women were diagnosed with chorioamnionitis due to fever in labor and also had acute SARS-CoV-2 infection. Conclusion Infants of mothers with SARS-CoV-2 in pregnancy had favorable short-term outcomes, with decrease in separation and increase in breastfeeding over this timeframe. Complex factors likely contribute to differences in birthweight and prematurity in the acute symptomatic group. Isolated fever in the setting of acute SARS-CoV-2 presents a dilemma regarding maternal chorioamnionitis, resulting in antibiotic exposure. Longitudinal follow-up is needed to determine infant outcomes (true hearing loss, development) following maternal SARS-CoV-2 infection.
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