Faculty Bibliography

As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209.

BACKGROUND:Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. METHODS:We studied 50 kidney transplant recipients following SARS-CoV-2 vaccination and quantified their anti-spike protein antibody, donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), and alloantibody formation. RESULTS:Participants were stratified using nucleocapsid testing as either SARS-CoV-2-naïve or experienced prior to vaccination. One of 34 (3%) SARS-CoV-2 naïve participants developed anti-spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS-CoV-2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre- and post-vaccination levels did not change for median dd-cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de-novo donor specific antibody status, or estimated glomerular filtration rate. CONCLUSIONS:SARS-CoV-2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS-CoV-2 infection.

BACKGROUND/UNASSIGNED:People who inject drugs (PWID) in Puerto Rico are disproportionately affected by the hepatitis C virus (HCV) epidemic. However, there is a scarcity of data on the HCV care cascade among PWID in Puerto Rico. This study aims to describe the HCV cascade of care among PWID in Puerto Rico, identify gaps, and explore barriers to HCV care. METHODS/UNASSIGNED:Participants were recruited using respondent-driven sampling and tested for both HCV antibodies (Ab) and RNA (ribonucleic acid) using rapid testing and dried blood spot samples (DBS). The cascade of care was estimated based on the DBS HCV Ab and RNA results, as well as self-reported data on HCV screening, linkage to care, treatment uptake and sustained virologic response collected through a questionnaire. The cascade was constructed sequentially, with each step using the number of people from the preceding step as the base denominator. The survey also assessed participants' perceived barriers to HCV care. RESULTS/UNASSIGNED:Out of 150 participants, 126 (84%) had previously been HCV screened, 87% (109/126) were HCV Ab positive, 72% (79/109) were RNA positive,48% (38/79) were linked to care, 32% (12/38) initiated treatment, 58% (7/12) finished treatment, and 71% (5/7) achieved SVR. Barriers to HCV care included concerns about drug abstinence requirements, access to transportation, stigma in healthcare settings, and lack of knowledge about HCV treatment sites. CONCLUSION/UNASSIGNED:This study provides insights into the HCV cascade of care among PWID in Puerto Rico for the first time and highlights limited diagnosis, treatment uptake, and barriers to care.

Hepatitis C virus (HCV) elimination is an important global public health goal. However, the United States (US) is not on track to meet the World Health Organization's 2030 targets for HCV elimination. Recently, the White House proposed an HCV elimination plan that includes point-of-care (POC) HCV RNA testing, which is currently in use in many countries, but is not approved in the US. POC HCV RNA testing is crucial for implementing community-based testing, and for enabling test-and-treat programs, assessing cure, and monitoring for reinfection.. In this commentary, we review the status of POC HCV RNA testing in the US, discuss factors that are needed for successful implementation, and issue specific public health and policy recommendations that would allow for the use of POC HCV RNA testing to support HCV elimination.

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.

BACKGROUND:Hepatitis C virus (HCV) treatment can effectively cure HCV among people who inject drugs (PWID). Perspectives of PWID treated in innovative models can reveal program features that address barriers to treatment, and guide implementation of similar models. METHODS:We interviewed 29 participants in the intervention arm of a randomized trial. The trial enrolled PWID with HCV in New York City from 2017 to 2020 and tested the effectiveness of a low-threshold HCV treatment model at a syringe services program. Participants were purposively sampled and interviewed in English or Spanish. The interview guide focused on prior experiences with HCV testing and treatment, and experiences during the trial. Interviews were inductively coded and analyzed using thematic analysis. RESULTS:Before enrollment, participants reported being tested for HCV in settings such as prison, drug treatment, and emergency rooms. Treatment was delayed because of not being seen as urgent by providers. Participants reported low self-efficacy, competing priorities, and systemic barriers to treatment such as insurance, waiting lists, and criminal-legal interactions. Stigma was a major factor. Treatment during the trial was facilitated through respect from staff, which overcame stigma. The flexible care model (allowing walk-ins and missed appointments) helped mitigate logistical barriers. The willingness of the staff to address social determinants of health was highly valued. CONCLUSION:Our findings highlight the need for low-threshold programs with nonjudgmental behavior from program staff, and flexibility to adapt to participants' needs. Social determinants of health remain a significant barrier, but programs' efforts to address these factors can engender trust and facilitate treatment. Trial registration NCT03214679.

As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209.

High error rates of viral RNA-dependent RNA polymerases lead to diverse intra-host viral populations during infection. Errors made during replication that are not strongly deleterious to the virus can lead to the generation of minority variants. However, accurate detection of minority variants in viral sequence data is complicated by errors introduced during sample preparation and data analysis. We used synthetic RNA controls and simulated data to test seven variant-calling tools across a range of allele frequencies and simulated coverages. We show that choice of variant caller and use of replicate sequencing have the most significant impact on single-nucleotide variant (SNV) discovery and demonstrate how both allele frequency and coverage thresholds impact both false discovery and false-negative rates. When replicates are not available, using a combination of multiple callers with more stringent cutoffs is recommended. We use these parameters to find minority variants in sequencing data from SARS-CoV-2 clinical specimens and provide guidance for studies of intra-host viral diversity using either single replicate data or data from technical replicates. Our study provides a framework for rigorous assessment of technical factors that impact SNV identification in viral samples and establishes heuristics that will inform and improve future studies of intra-host variation, viral diversity, and viral evolution. IMPORTANCE When viruses replicate inside a host cell, the virus replication machinery makes mistakes. Over time, these mistakes create mutations that result in a diverse population of viruses inside the host. Mutations that are neither lethal to the virus nor strongly beneficial can lead to minority variants that are minor members of the virus population. However, preparing samples for sequencing can also introduce errors that resemble minority variants, resulting in the inclusion of false-positive data if not filtered correctly. In this study, we aimed to determine the best methods for identification and quantification of these minority variants by testing the performance of seven commonly used variant-calling tools. We used simulated and synthetic data to test their performance against a true set of variants and then used these studies to inform variant identification in data from SARS-CoV-2 clinical specimens. Together, analyses of our data provide extensive guidance for future studies of viral diversity and evolution.

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.

The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This article represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.