The 2000HIV study: Design, multi-omics methods and participant characteristics.

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets. Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort. Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine. Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.

Temporal Trends of Optn Hope Act Variance Participation

Purpose: The Organ Procurement and Transplantation Network (OPTN) created a research variance allowing for transplantation of HIV+ donor kidneys and livers into HIV+ recipients after passage of the HIV Organ Policy Equity (HOPE) Act legislation in 2013 and subsequent published research criteria in November 2015. In May 2020 the OPTN modified the variance to include all solid organs. Method(s): The OPTN database was used to analyze temporal trends in waiting list registrations, HIV+ donors, HOPE transplant recipients, and program participation in the OPTN HOPE Act variance. HIV+ donors were identified through HIV serology/ NAT fields collected by the OPTN;recipients of these organs are HOPE recipients. Result(s): Transplant program participation saw consistent growth but has remained stable for the two years (Fig A). Despite this, patient demand for HOPE kidneys has been simultaneously declining, perhaps driven by a decline in listings related to Hypertensive Nephrosclerosis and DM Type II (listings for HIV Nephropathy remained stable), while liver demand remains low but stable (Fig B). Concurrently, there has been a consistent volume of recovered HIV+ donors and organs transplanted (Fig C, D). Transplant volume recently exceeded 300 organs transplanted (300 deceased donor, 3 living donor), largely driven by kidney (236 kidney, 67 liver;11 SLK) from 187 recovered HIV+ donors. Living donation of HIV+ organs remains limited to kidney. Among HIV+ deceased donors, the kidney discard rate was 32% while the liver discard rate was 4%. Twenty-nine recovered deceased donors had no organs transplanted, and associated common discard reasons for these donors were exhausted match runs and biopsy findings. Conclusion(s): The OPTN database does not include HIV status at listing;therefore, the decline in demand cannot be attributed to potential access changes for HIV+ patients, but may be related to the impacts of the COVID-19 pandemic. The impacts of the COVID-19 pandemic have not noticeably affected HOPE Act transplant volumes, highlighting the resiliency of the US transplant system. Based on consistent activity and positive data and safety analyses through five years, the OPTN recommended removal of the research criteria as a potential barrier to expanded utilization of the HOPE Act to HHS, in turn making HIV-to-HIV transplantation standard of care;the result of that recommendation is pending. (Figure Presented).

School Connectedness and e-cigarette Susceptibility and Use in a Diverse Urban Adolescent Sample

Purpose: Adolescent school connectedness, particularly positive relationships with teachers, generally protects from health risk behaviors such as tobacco use, yet how this relates to adolescent e-cigarette use has not yet been described. This study examines the relationship between school connectedness and e-cigarette susceptibility and use in a diverse adolescent longitudinal sample. Methods: This is a secondary analysis of a school-based intervention including ten public schools in one urban school district. We surveyed 661 middle (66.6% eighth grade) and high school (33.4% eleventh grade) student participants at three time points between spring 2019 and spring 2020. The 2020 surveys were completed early in the COVID-19 pandemic, prior to the transition to remote learning. Respondents had a mean age of 14.1 years, were 53% female, and 28% identified as non-Hispanic white,15.6% as Hispanic, 23.8% as Black, 29.8% as Asian, and 2.9% as American Indian/Alaska Native. Ordinal logistic regression models examined unadjusted and adjusted associations between school connectedness (both baseline and concurrent) and an ordinal measure of e-cigarette susceptibility (any vs. none) and use (any vs. no past 30-day use) at all three time points. Covariates in the adjusted models included grade, intervention condition, English language learner status, gender, race/ethnicity, baseline use of any tobacco, and baseline weighted grade point average. Results: Levels of any tobacco use were low in the spring of 2019 (3.8%), e-cigarettes represented the predominant form of tobacco use (2.4%), and most respondents reported no e-cigarette susceptibility (69%). E-cigarette susceptibility and use remained relatively stable during the follow-up period. Higher levels of baseline school connectedness were consistently associated with lower odds of e-cigarette susceptibility/use in spring 2019 (OR: 0.37, 95% CI: 0.26, 0.53), fall 2019 (OR: 0.51, 95% CI: 0.35, 0.74), and spring 2020 (OR: 0.47, 95% CI: 0.30, 0.73). Higher levels of concurrent school connectedness were also associated with lower odds of e-cigarette susceptibility/use over time: spring 2019 (OR: 0.36, 95% CI: 0.25, 0.51), fall 2019 (OR: 0.48, 95% CI: 0.34, 0.66), and spring 2020 (OR: 0.65, 95% CI: 0.42, 0.99). Findings were similar for eighth and eleventh graders and did not differ significantly both before and after adjusting for other covariates. Conclusions: Both adolescents’ baseline levels of connection to their schools and their connectedness over time appear to serve as protective factors for e-cigarette susceptibility and use. These findings highlight the importance of promoting positive school experiences and strong teacher-student relationships as a mechanism of reducing adolescent risk behaviors such as e-cigarette use among diverse adolescent populations. Sources of Support: This project was funded by a grant from the National Institute of Minority Health and Health Disparities (NIMHD) grant number R01MD010586 (PI: Allen).

Incidence and time to resolution of axillary adenopathy on mammography after COVID-19 vaccination

Background: This study reports incidence, timing, characteristics, and surveillance imaging of mammographic axillary adenopathy following COVID-19 vaccination. As COVID-19 immunizations continue, with possible booster vaccines upcoming, this study offers timing considerations and potential follow-up recommendations for breast imaging after vaccination. Methods: Retrospective analysis of patients (pts) who received at least one COVID-19 vaccine prior to screening (SM) or diagnostic mammography (DM) at Mayo Clinic Florida between January 15 to May 31, 2021. Vaccine-related information was queried by mammography technologists. Adenopathy was assessed by interpreting radiologists and follow-up studies were collated. Mammogram adenopathy included single enlarged node, multiple enlarged nodes, and adenopathy with soft tissue stranding. Ultrasound adenopathy included mildly prominent nodes with preserved fatty hila to rounded nodes with apparent loss of a fatty hilum. Wilcoxon rank-sum test and Fisher's exact test were used to compare continuous and categorical variables, respectively. Multivariable logistic regression model was used to evaluate the association between days from vaccine and adenopathy. Results: Of 2349 pts, 34 (1.4%) had adenopathy (DM=6;SM=28) and 3 (0.1%) were symptomatic. Presence of axillary symptoms was associated with abnormal imaging (p<0.001) with an odds ratio of 33 in multivariable model. Median time after vaccine for pts with adenopathy was significantly shorter at S 14 days compared to 33 days for pts without adenopathy (p<0.001). Incidence of adenopathy decreased as days from vaccine increased (3.4% for 0-14 days, 2.1% for 15-28 days, and 0.4% for > 28 days, p<0.001). After adjusting for being symptomatic, days from vaccine still had a significant impact on finding mammographic adenopathy (for each day after vaccine, OR=0.96, p<0.001). No significant difference was seen based on age (p=0.66), vaccine brand (p=0.66), vaccine dose (p=0.18). ROC analysis to identify a cutoff value for presence/absence of adenopathy was 0.74 (95% CI 0.67-0.81) at 22.5 days following vaccination. Additional imaging with mammogram and/or ultrasound was requested for 31 pts. These included no follow-up (n=4, 12.9%), repeat ultrasound with or without mammogram in 1-3 months (n=26, 83.9%), and biopsy (n=1, 3.2%, pt with ipsilateral breast cancer with negative results, presumably vaccine induced). To date, all pts who underwent surveillance imaging demonstrated normalization of lymph node appearance. The median time for abnormal imaging related to adenopathy to return to BI-RADS 1 or 2 was 84 (range 13-157) days. Conclusion: The incidence of COVID-19 vaccine-induced adenopathy in this study (1.4%) appeared to be lower than self-reported axillary swelling in COVID-19 vaccine trials (16%) but is still higher than the reported incidence of adenopathy on an otherwise normal SM (0.02-0.04%). The incidence of adenopathy decreased significantly over time and was not present in most pts 28 days after the vaccine. In patients with abnormal adenopathy, followup imaging showed resolution of vaccine-induced adenopathy in most patients by 3 months.

Rationale and process for N95 respirator sanitation and reuse in the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: The novel severe acute respiratory coronavirus virus 2 (SARS-CoV-2) was first reported in Wuhan, China, in December 2019 and is notable for being highly contagious and potentially lethal; and SARS-CoV-2 is mainly spread by droplet transmission. The US healthcare system's response to the COVID-19 pandemic has been challenged by a shortage of personal protective equipment (PPE), especially N95 respirators. Restricted use, reuse, and sanitation of PPE have been widely adopted to provide protection for frontline healthcare workers caring for often critically ill and highly contagious patients. Here, we describe our validated process for N95 respirator sanitation. DESIGN: Process development, validation, and implementation. SETTING: Level 1, urban, academic, medical center. METHODS: A multidisciplinary team developed a novel evidence-based process for N95 respirator reprocessing and sanitation using ultraviolet (UV) light. Dose measurement, structural integrity, moisture content, particle filtration, fit testing, and environmental testing were performed for both quality control and validation of the process. RESULTS: The process achieved UV light dosing for sanitation while maintaining the functional and structural integrity of the N95 respirators, with a daily potential throughput capacity of ∼12,000 masks. This process has supported our health system to provide respiratory PPE to all frontline team members. CONCLUSIONS: This novel method of N95 respirator sanitation can safely enable reuse of the N95 respirators essential for healthcare workers caring for patients with COVID-19. Our high-throughput process can extend local supplies of this critical PPE until the national supply is replenished.

Evaluation of tocilizumab in patients with COVID-19 in the intensive care unit

INTRODUCTION: Tocilizumab is a monoclonal antibody targeted against the IL-6 receptor and is recommended for the treatment of rheumatoid arthritis, giant cell arteritis, and cytokine release syndrome induced by CAR-T therapy. Tocilizumab is being investigated as a treatment option for COVID-19, as these patients have been shown to be at an increased risk for cytokine storming. There is conflicting data between retrospective and prospective trials for tocilizumab. The purpose of this study was to evaluate the use of tocilizumab in patients with COVID-19 in the intensive care unit. METHODS: This was a single-center, retrospective, cohort study of ICU patients who received a one-time dose of tocilizumab 400mg IV for COVID-19 between March 19, 2020 and June 29, 2020. The primary outcome of this study was in-hospital mortality and the secondary outcome was secondary infections. Other data points collected included time from symptom onset to administration, time to death after administration, baseline APACHE-II score, baseline and 72-hour post-tocilizumab ventilatory status, vasopressor and paralytic requirements. RESULTS: Thirty-six patients were included. Median age was 59 [45-73] years and 26 (72.7%) subjects were male. Average weight and BMI were 101.8 kg and 35 kg/m2 in patients who expired versus 85.8 kg and 28 kg/m2 in patients who survived. Median mg/kg dose for patients that expired was 3.77 versus 5.16 in patients who survived. The average baseline APACHE-II score was 25 compared to 16 in patients who expired versus patients who survived. Average time from symptom onset to tocilizumab administration was 11.7 days. In-hospital mortality was 58.3%. Average time to death was 17 days. Secondary infection occurred in 8 (22%) patients. At baseline 15 (42%) patients who expired versus 6 (40%) patients who survived were mechanically ventilated, compared to 18 (86%) patients and 9 (60%) patients posttocilizumab administration. No trend was seen in baseline versus 72-hour post PaO2/FiO2 ratio, ferritin, ALT, CK, WBC, platelet count, CRP, or D-dimer. CONCLUSIONS: It is unclear if tocilizumab provides clinical benefit for patients admitted to the ICU with COVID-19. Patients who survived had lower baseline APACHE scores and received higher tocilizumab doses.

Utilization of an Orthopedic Hood as Personal Protective Equipment for Intubation of Coronavirus Patients: a Brief Technical Report.

BACKGROUND: The novel coronavirus disease (COVID-19) has afflicted millions of people worldwide since its first case was reported in December 2019. Personal protective equipment (PPE) has been tailored accordingly, but as of April 2020, close to 10 000 health care workers in the United States have contracted COVID-19 despite wearing recommended PPE. As such, standard guidelines for PPE may be inadequate for the health care worker performing high-risk aerosolizing procedures such as endotracheal intubation. In this brief technical report, we describe the integration of an orthopedic hood cover as an item for full barrier protection against COVID-19 transmission. TECHNICAL DESCRIPTION: The Coronavirus Airway Task Force at Virginia Commonwealth University Medical Center approved this initiative and went live with the full barrier suit during the last week of March 2020. The PPE described in this report includes a Stryker T4 Hood, normally used in conjunction with the Stryker Steri-Shield T4 Helmet. Instead of the helmet, the hood is secured to the head via a baseball cap and binder clip. This head covering apparatus is to be used as an accessory to other PPE items that include an N95 mask, waterproof gown, and disposable gloves. The motor ventilation system is not used in order to prevent airborne viral entry into the hood. DISCUSSION: An advantage of the full barrier suit is an additional layer of droplet protection during intubation. The most notable disadvantage is the absence of a ventilation system within the hood covering. CONCLUSION: Modification of existing PPE may provide protection for health care workers during high-risk aerosolizing procedures such as endotracheal intubation. Although the integration of this medical equipment meets the immediate needs of an escalating crisis, further innovation is on the horizon. More research is needed to confirm the safety of modified PPE.