Background. Antibody-based strategies for COVID-19 have shown promise in prevention and treatment of early disease. COVID-19 convalescent plasma (CCP) has been widely used but results from randomized trials supporting its benefit in hospitalized patients with pneumonia are limited. Here, we assess the efficacy of CCP in severely ill, hospitalized adults with COVID-19 pneumonia. Methods. We performed a randomized control trial (PennCCP2), with 80 adults hospitalized with COVID-19 pneumonia, comparing up to 2 units of locally sourced CCP plus standard care versus standard care alone. The primary efficacy endpoint was comparison of a clinical severity score. Key secondary outcomes include 14- and 28-day mortality, 14- and 28-day maximum 8-point WHO ordinal score (WHO8) score, duration of supplemental oxygenation or mechanical ventilation, respiratory SARS-CoV-2 RNA, and anti–SARS-CoV-2 antibodies. Results. Eighty hospitalized adults with confirmed COVID-19 pneumonia were enrolled at median day 6 of symptoms and day 1 of hospitalization; 60% were anti–SARS-CoV-2 antibody seronegative. Participants had a median of 3 comorbidities, including risk factors for severe COVID-19 and immunosuppression. CCP treatment was safe and conferred significant benefit by clinical severity score (median [MED] and interquartile range [IQR] 10 [5.5–30] vs. 7 [2.75–12.25], P = 0.037) and 28-day mortality (n = 10, 26% vs. n = 2, 5%; P = 0.013). All other prespecified outcome measures showed weak evidence toward benefit of CCP. Conclusion. Two units of locally sourced CCP administered early in hospitalization to majority seronegative participants conferred a significant benefit in clinical severity score and 28-day mortality. Results suggest CCP may benefit select populations, especially those with comorbidities who are treated early. Trial Registration. ClinicalTrials.gov NCT04397757. Funding. University of Pennsylvania.

Objective: There is mounting evidence that neighborhoods contribute to perinatal health inequity. We aimed (1) to determine whether neighborhood deprivation (a composite marker of area-level poverty, education, and housing) is associated with early pregnancy impaired glucose intolerance (IGT) and pre-pregnancy obesity and (2) to quantify the extent to which neighborhood deprivation may explain racial disparities in IGT and obesity. Study Design: This was a retrospective cohort study of non-diabetic patients with singleton births ≥ 20 weeks’ gestation from 1 January 2017–31 December 2019 in two Philadelphia hospitals. The primary outcome was IGT (HbA1c 5.7–6.4%) at <20 weeks’ gestation. Addresses were geocoded and census tract neighborhood deprivation index (range 0–1, higher indicating more deprivation) was calculated. Mixed-effects logistic regression and causal mediation models adjusted for covariates were used. Results: Of the 10,642 patients who met the inclusion criteria, 49% self-identified as Black, 49% were Medicaid insured, 32% were obese, and 11% had IGT. There were large racial disparities in IGT (16% vs. 3%) and obesity (45% vs. 16%) among Black vs. White patients, respectively (p < 0.0001). Mean (SD) neighborhood deprivation was higher among Black (0.55 (0.10)) compared with White patients (0.36 (0.11)) (p < 0.0001). Neighborhood deprivation was associated with IGT and obesity in models adjusted for age, insurance, parity, and race (aOR 1.15, 95%CI: 1.07, 1.24 and aOR 1.39, 95%CI: 1.28, 1.52, respectively). Mediation analysis revealed that 6.7% (95%CI: 1.6%, 11.7%) of the Black-White disparity in IGT might be explained by neighborhood deprivation and 13.3% (95%CI: 10.7%, 16.7%) by obesity. Mediation analysis also suggested that 17.4% (95%CI: 12.0%, 22.4%) of the Black–White disparity in obesity may be explained by neighborhood deprivation. Conclusion: Neighborhood deprivation may contribute to early pregnancy IGT and obesity–surrogate markers of periconceptional metabolic health in which there are large racial disparities. Investing in neighborhoods where Black patients live may improve perinatal health equity.

Preterm birth (PTB) remains a key public health issue that disproportionately affects Black individuals. Since spontaneous PTB (sPTB) and medically indicated PTB (mPTB) may have different causes and interventions, we quantified racial disparities for sPTB and mPTB, and we characterized the geographic patterning of these phenotypes, overall and according to race/ethnicity. We examined a pregnancy cohort of 83,952 singleton births at 2 Philadelphia hospitals from 2008–2020, and classified each PTB as sPTB or mPTB. We used binomial regression to quantify the magnitude of racial disparities between non-Hispanic Black and non-Hispanic White individuals, then generated small area estimates by applying a Bayesian model that accounts for small numbers and smooths estimates of PTB risk by borrowing information from neighboring areas. Racial disparities in both sPTB and mPTB were significant (relative risk of sPTB = 1.83, 95% confidence interval: 1.70, 1.98; relative risk of mPTB = 2.20, 95% confidence interval: 2.00, 2.42). The disparity was 20% greater in mPTB than sPTB. There was substantial geographic variation in PTB, sPTB, and mPTB risks and racial disparity. Our findings underscore the importance of distinguishing PTB phenotypes within the context of public health and preventive medicine. Future work should consider social and environmental exposures that may explain geographic differences in PTB risk and disparities.

Infants born preterm are at risk of neonatal morbidity and mortality. Preterm birth (PTB) can be categorized as either spontaneous (sPTB) or medically indicated (mPTB), resulting from distinct pathophysiologic processes such as preterm labor or preeclampsia, respectively. A growing body of literature has demonstrated the impacts of nitrogen dioxide (NO₂) and benzene exposure on PTB, though few studies have investigated how these associations may differ by PTB subtype. We investigated the associations of NO₂ and benzene exposure with sPTB and mPTB among 18,616 singleton live births at two Philadelphia hospitals between 2013 and 2017. Residential NO₂ exposure was estimated using a land use regression model and averaged over the patient’s full pregnancy. Benzene exposure was estimated at the census tract level using National Air Toxics Assessment (NATA) exposure data from 2014. We used logistic mixed-effects models to calculate odds ratios for overall PTB, sPTB, and mPTB separately, adjusting for patient- and tract-level confounders. Given the known racial segregation and PTB disparities in Philadelphia, we also examined race-stratified models. Counter to the hypothesis, neither NO₂ nor benzene exposure differed by race, and neither were significantly associated with PTB or PTB subtypes. As such, these pollutants do not appear to explain the racial disparities in PTB in this setting.