Faculty Bibliography

BACKGROUND AND OBJECTIVES/UNASSIGNED:Maternal vaccination may prevent infant coronavirus disease 2019 (COVID-19). We aimed to quantify protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant's life. METHODS/UNASSIGNED:Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine (nonboosted or boosted, respectively) had full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G, and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers measured at delivery. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by verified maternal-report and laboratory confirmation through prospective follow-up to 6 months of age between December 2021 and July 2022. The risk reduction for infection by dose group and antibody titer level was estimated in separate models. RESULTS/UNASSIGNED:Infants of boosted mothers (n = 204) had significantly higher Spike IgG, pseudovirus, and live nAb titers at delivery than infants of nonboosted mothers (n = 271), and were 56% less likely to acquire infection in the first 6 months (P = .03). Irrespective of boost, for each 10-fold increase in Spike IgG titer at delivery, the infant's risk of acquiring infection was reduced by 47% (95% confidence interval 8%-70%; P = .02). Similarly, a 10-fold increase in pseudovirus titers against Wuhan Spike, and live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery were associated with a 30%, 46%, 56%, and 60% risk reduction, respectively. CONCLUSIONS/UNASSIGNED:Higher transplacental binding and nAb titers substantially reduced the risk of SARS-CoV-2 infection in infants, and a booster dose amplified protection during a period of omicron predominance. Until infants are age-eligible for vaccination, maternal vaccination provides passive protection against symptomatic infection during early infancy.

The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44-0.88 log₁₀ higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55-1.77 for IgG, 1.00-1.78 for live virus nAb and 1.79-2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.

COVID-19 vaccines were developed at unparalleled speed, but racial disparities persist in vaccine uptake. This is a cross-sectional survey that was conducted in mid-2021 in ambulatory clinics across Brooklyn, New York. The objectives of the study were to assess: knowledge of COVID-19, healthcare communication and access, attitudes including trust in the process of vaccine development and mistrust due to racial discrimination, and to determine the relationship of the above to vaccine receipt. 58 respondents self-identified as Black non-Hispanic and completed the survey: the majority were women (79%), <50 years old (65%), employed (66%), and had annual household income <$75,000 (59%). The majority reported having some health insurance (97%) and a regular place of healthcare (95%). 60% of respondents reported COVID-19 vaccination receipt. A significant percentage of the vaccinated group compared to the unvaccinated group scored higher on knowledge questions (91% vs. 65%; p = 0.018), felt it was important that others in the community get vaccinated (89% vs. 65%, p = 0.04), and trusted vaccine safety (86% vs. 35%; p < 0.0001) and effectiveness (88% vs. 48%; p < 0.001). The unvaccinated group reported a lower annual household income of <$75,000 (72% vs. 50%; p = 0.0002) and also differed by employment status (p = 0.04). Majority in both groups agreed that racial discrimination interferes with healthcare (78%). In summary, unvaccinated Black non-Hispanic respondents report significant concerns about vaccine safety and efficacy and have greater mistrust in the vaccine development process. The relationship between racial discrimination, mistrust, and vaccine hesitancy needs further study in order to improve vaccine uptake in this population.

BACKGROUND:Among those at highest risk for COVID-19 exposure is the large population of frontline essential workers in occupations such food service, retail, personal care, and in-home health services, among whom Black and Latino/Hispanic persons are over-represented. For those not vaccinated and at risk for exposure to COVID-19, including frontline essential workers, regular (approximately weekly) COVID-19 testing is recommended. However, Black and Latino/Hispanic frontline essential workers in these occupations experience serious impediments to COVID-19 testing at individual/attitudinal- (e.g., lack of knowledge of guidelines), social- (e.g., social norms), and structural-levels of influence (e.g., poor access), and rates of testing for COVID-19 are insufficient. METHODS/DESIGN:The proposed community-engaged study uses the multiphase optimization strategy (MOST) framework and an efficient factorial design to test four candidate behavioral intervention components informed by an integrated conceptual model that combines critical race theory, harm reduction, and self-determination theory. They are A) motivational interview counseling, B) text messaging grounded in behavioral economics, C) peer education, and D) access to testing (via navigation to an appointment vs. a self-test kit). All participants receive health education on COVID-19. The specific aims are to: identify which components contribute meaningfully to improvement in the primary outcome, COVID-19 testing confirmed with documentary evidence, with the most effective combination of components comprising an "optimized" intervention that strategically balances effectiveness against affordability, scalability, and efficiency (Aim 1); identify mediators and moderators of the effects of components (Aim 2); and use a mixed-methods approach to explore relationships among COVID-19 testing and vaccination (Aim 3). Participants will be N = 448 Black and Latino/Hispanic frontline essential workers not tested for COVID-19 in the past six months and not fully vaccinated for COVID-19, randomly assigned to one of 16 intervention conditions, and assessed at 6- and 12-weeks post-baseline. Last, N = 50 participants will engage in qualitative in-depth interviews. DISCUSSION:This optimization trial is designed to yield an effective, affordable, and efficient behavioral intervention that can be rapidly scaled in community settings. Further, it will advance the literature on intervention approaches for social inequities such as those evident in the COVID-19 pandemic. TRIAL REGISTRATION:ClinicalTrials.gov: NCT05139927 ; Registered on 11/29/2021. Protocol version 1.0. May 2, 2022, Version 1.0.

Importance/UNASSIGNED:There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective/UNASSIGNED:To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants/UNASSIGNED:CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions/UNASSIGNED:A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures/UNASSIGNED:The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results/UNASSIGNED:Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance/UNASSIGNED:In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04364737.

In the era of highly active antiretroviral therapy (HAART), disseminated Kaposi sarcoma (KS) has become much rarer in the USA. We report a case of a 34-year-old man with KS of the skin, oropharynx, lung and rectum. Within the same lung nodule, we discovered significant burden of colesional Cryptococcus neoformans, in the context of a positive asymptomatic cryptococcal antigenemia, which was a previously unreported occurrence. The gold standard of treatment for KS continues to be HAART. The role of chemotherapy is still controversial. In addition, a cryptococcal antigen screen-and-treat approach with fluconazole is still not routinely recommended in the USA to prevent serious meningeal disease despite recent studies showing efficacy and applicability. We discuss both issues here and the outcome of our patient. We also present the patient's own unique perspective in dealing with the ramifications of these diagnoses.

We report a laboratory-confirmed case of adult intestinal toxemia botulism in an allogeneic hematopoietic stem cell transplantation (allo-HCT) recipient. Onset of symptoms occurred within the hospitalized setting, making this case particularly unique. Botulism may have arisen because of significant intestinal disruption and compromise, and not directly from immune compromise.

Diffractive waveplates and equivalent metasurfaces provide a promising path for applications in thin film beam steering, tunable lenses, and polarization filters. However, fixed metasurfaces alone are unable to be tuned electronically. By combining metasurfaces with tunable liquid crystals, we experimentally demonstrate a single layer device capable of electrically switching a diffractive waveplate design at a measured peak diffraction efficiency of 35%, and a minimum switching voltage of 10V. Furthermore, the nano-scale metasurface aligned liquid crystals are largely independent of variations in wavelength and temperature. We also present a computational analysis of the efficiency limits of liquid crystal based diffractive waveplates, and compare this analysis to experimental measurements.

PURPOSE/OBJECTIVE:An adverse drug reaction associated with the use of prasugrel for dual antiplatelet therapy after percutaneous coronary intervention (PCI) with stent placement is reported. SUMMARY/CONCLUSIONS:About one week after starting prasugrel use following angioplasty and a stent revision procedure, a 61-year-old woman arrived in the emergency department with wheezing, shortness of breath, a feeling of throat closure, and a widespread erythematous, maculopapular, pruritic rash. She reported that the respiratory symptoms had started to develop the previous day, with the onset of rash occurring about 24 hours after initiation of prasugrel therapy. The patient's symptoms subsided after administration of 0.3 mg epinephrine subcutaneously, diphenhydramine 50 mg i.v., and methylprednisolone 125 mg i.v. Prasugrel was discontinued, and the patient was switched to another P2Y12 inhibitor (ticagrelor) for continued dual antiplatelet therapy. Analysis of the case using the adverse drug reaction probability scale of Naranjo et al. indicated that prasugrel was the probable cause of the hypersensitivity reaction. Hypersensitivity manifesting as a rash has been previously reported in patients receiving prasugrel, a thienopyridine P2Y12 inhibitor. Desensitization may be an option for thienopyridine-allergic patients undergoing PCI with stenting; alternatively, the nonthienopyridine P2Y12 inhibitor ticagrelor may be used in a dual antiplatelet therapy regimen. CONCLUSION/CONCLUSIONS:A patient who had undergone PCI with stenting developed shortness of breath and rash associated with prasugrel therapy. Symptoms abated after supportive therapy and discontinuation of prasugrel, the probable offending agent. Treatment was safely switched to ticagrelor.