The Role of Staff in Transmission of SARS-CoV-2 in Long-term Care Facilities.

BACKGROUND: US long-term care facilities (LTCFs) have experienced a disproportionate burden of COVID-19 morbidity and mortality. METHODS: We examined SARS-CoV-2 transmission among residents and staff in 60 LTCFs in Fulton County, Georgia, from March 2020 to September 2021. Using the Wallinga-Teunis method to estimate the time-varying reproduction number, R(t), and linear-mixed regression models, we examined associations between case characteristics and R(t). RESULTS: Case counts, outbreak size and duration, and R(t) declined rapidly and remained low after vaccines were first distributed to LTCFs in December 2020, despite increases in community incidence in summer 2021. Staff cases were more infectious than resident cases (average individual reproduction number, R i = 0.6 [95% confidence intervals [CI] = 0.4, 0.7] and 0.1 [95% CI = 0.1, 0.2], respectively). Unvaccinated resident cases were more infectious than vaccinated resident cases (R i = 0.5 [95% CI = 0.4, 0.6] and 0.2 [95% CI = 0.0, 0.8], respectively), but estimates were imprecise. CONCLUSIONS: COVID-19 vaccines slowed transmission and contributed to reduced caseload in LTCFs. However, due to data limitations, we were unable to determine whether breakthrough vaccinated cases were less infectious than unvaccinated cases. Staff cases were six times more infectious than resident cases, consistent with the hypothesis that staff were the primary drivers of SARS-CoV-2 transmission in LTCFs.

Implementation of close contact elicitation at the time of COVID-19 testing-Atlanta, GA, October-November 2020.

BACKGROUND: Contact tracing during the Coronavirus Disease 2019 (COVID-19) pandemic in the USA has been met with various challenges. In an attempt to improve the yield of close contact collection, the Fulton County Board of Health implemented a pilot approach to contact elicitation at the time of testing. METHODS: Between October and November 2020, close contacts were elicited from persons under investigation (PUIs) at one COVID-19 testing site in Fulton County, GA. Secure online data collection forms were used to record PUI demographic data, close contact information and reasons for not providing contacts. RESULTS: Of 1238 PUIs, 48% reported at least one contact. Among the 66 people who tested positive, 16 (24%) reported contacts compared to 578/1165 (50%) who tested negative. PUIs of increasing age were less likely to provide contacts; Black and Hispanic PUIs were also less likely to report any contacts compared to White and Asian PUIs. CONCLUSIONS: Our study revealed that PUIs testing positive were less likely to provide contacts compared to PUIs testing negative. Age and racial differences were also noted in the provision of contacts. Further investigation is needed to understand these discrepancies in order to devise more effective strategies for contact elicitation.

Biomaterials-aided mandibular reconstruction using in vivo bioreactors.

Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry without the addition of exogenous growth factors or cells. To translate this technology, we investigated its success in reconstructing a mandibular defect of physiologically relevant size in sheep. We fabricated and implanted 3D-printed in vivo bioreactors against rib periosteum and utilized biomaterial-based space maintenance to preserve the native anatomical mandibular structure in the defect site before reconstruction. Nine weeks after bioreactor implantation, the ovine mandibles were repaired with the autologous bony tissue generated from the in vivo bioreactors. We evaluated tissues generated in bioreactors by radiographic, histological, mechanical, and biomolecular assays and repaired mandibles by radiographic and histological assays. Biomaterial-aided mandibular reconstruction was successful in a large superior marginal defect in five of six (83%) sheep. Given that these studies utilized clinically available biomaterials, such as bone cement and ceramic particles, this strategy is designed for rapid human translation to improve outcomes in patients with large mandibular defects.

Coronavirus Disease 2019 (COVID-19) Prevalences Among People Experiencing Homelessness and Homelessness Service Staff During Early Community Transmission in Atlanta, Georgia, April-May 2020.

BACKGROUND: In response to reported coronavirus disease 2019 (COVID-19) outbreaks among people experiencing homelessness (PEH) in other US cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and associated symptoms, and review shelter infection prevention and control (IPC) policies. METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during 7 April-6 May 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire. RESULTS: Overall, 2875 individuals at 24 shelters and 9 unsheltered outreach events underwent SARS-CoV-2 testing, and 2860 (99.5%) had conclusive test results. The SARS-CoV-2 prevalences were 2.1% (36/1684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases, compared with RT-PCR. Prevalences by shelter ranged 0-27.6%. Repeat testing 3-4 weeks later at 4 shelters documented decreased SARS-CoV-2 prevalences (0-3.9%). Of 24 shelters, 9 completed shelter assessments and implemented IPC measures as part of the COVID-19 response. CONCLUSIONS: PEH living in shelters experienced a higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for the identification and isolation of COVID-19 cases, and is an important strategy to interrupt SARS-CoV-2 transmission.

Estimating the Unknown: Greater Racial and Ethnic Disparities in COVID-19 Burden After Accounting for Missing Race and Ethnicity Data.

BACKGROUND: Black, Hispanic, and Indigenous persons in the United States have an increased risk of SARS-CoV-2 infection and death from COVID-19, due to persistent social inequities. However, the magnitude of the disparity is unclear because race/ethnicity information is often missing in surveillance data. METHODS: We quantified the burden of SARS-CoV-2 notification, hospitalization, and case fatality rates in an urban county by racial/ethnic group using combined race/ethnicity imputation and quantitative bias analysis for misclassification. RESULTS: The ratio of the absolute racial/ethnic disparity in notification rates after bias adjustment, compared with the complete case analysis, increased 1.3-fold for persons classified Black and 1.6-fold for those classified Hispanic, in reference to classified White persons. CONCLUSIONS: These results highlight that complete case analyses may underestimate absolute disparities in notification rates. Complete reporting of race/ethnicity information is necessary for health equity. When data are missing, quantitative bias analysis methods may improve estimates of racial/ethnic disparities in the COVID-19 burden.

Rapid Scale-up of an Antiretroviral Therapy Program Before and During the COVID-19 Pandemic - Nine States, Nigeria, March 31, 2019-September 30, 2020.

In 2018, an estimated 1.8 million persons living in Nigeria had HIV infection (1.3% of the total population), including 1.1 million (64%) who were receiving antiretroviral therapy (ART) (1). Effective ART reduces morbidity and mortality rates among persons with HIV infection and prevents HIV transmission once viral load is suppressed to undetectable levels (2,3). In April 2019, through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR),* CDC launched an 18-month ART Surge program in nine Nigerian states to rapidly increase the number of persons with HIV infection receiving ART. CDC analyzed programmatic data gathered during March 31, 2019-September 30, 2020, to describe the ART Surge program's progress on case finding, ART initiation, patient retention, and ART Surge program growth. Overall, the weekly number of newly identified persons with HIV infection who initiated ART increased approximately eightfold, from 587 (week ending May 4, 2019) to 5,329 (week ending September 26, 2020). The ART Surge program resulted in 208,202 more HIV-infected persons receiving PEPFAR-supported ART despite the COVID-19 pandemic (97,387 more persons during March 31, 2019-March 31, 2020 and an additional 110,815 persons during April 2020-September 2020). Comprehensive, data-guided, locally adapted interventions and the use of incident command structures can help increase the number of persons with HIV infection who receive ART, reducing HIV-related morbidity and mortality as well as decreasing HIV transmission.

Preventing COVID-19 Outbreaks in Long-Term Care Facilities Through Preemptive Testing of Residents and Staff Members - Fulton County, Georgia, March-May 2020.

Long-term care facility (LTCF) residents are at particularly high risk for morbidity and mortality associated with infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), given their age and high prevalence of chronic medical conditions, combined with functional impairment that often requires frequent, close contact with health care providers, who might inadvertently spread the virus to residents (1,2). During March-May 2020 in Fulton County, Georgia, >50% of COVID-19-associated deaths occurred among LTCF residents, although these persons represented <1% of the population (3,4). Mass testing for SARS-CoV-2 has been an effective strategy for identifying asymptomatic and presymptomatic infections in LTCFs (5). This analysis sought to evaluate the timing at which mass testing took place in relation to the known presence of a COVID-19 infection and the resulting number of infections that occurred. In 15 LTCFs that performed facility-wide testing in response to an identified case, high prevalences of additional cases in residents and staff members were found at initial testing (28.0% and 7.4%, respectively), suggesting spread of infection had already occurred by the time the first case was identified. Prevalence was also high during follow-up, with a total of 42.4% of residents and 11.8% of staff members infected overall in the response facilities. In comparison, 13 LTCFs conducted testing as a preventive strategy before a case was identified. Although the majority of these LTCFs identified at least one COVID-19 case, the prevalence was significantly lower at initial testing in both residents and staff members (0.5% and 1.0%, respectively) and overall after follow-up (1.5% and 1.7%, respectively). These findings indicate that early awareness of infections might help facilities prevent potential outbreaks by prioritizing and adhering more strictly to infection prevention and control (IPC) recommendations, resulting in fewer infections than would occur when relying on symptom-based screening (6,7).

Epidemiology of Pediatric Multidrug-Resistant Tuberculosis in the United States, 1993-2014.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an important global public health threat, but accurate estimates of MDR-TB burden among children are lacking. METHODS: We analyzed demographic, clinical, and laboratory data for newly diagnosed pediatric (age <15 years) TB cases reported to the US National TB Surveillance System during 1993-2014. MDR-TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To ascertain potential underestimation of pediatric MDR-TB, we surveyed high-burden states for clinically diagnosed cases treated for MDR-TB. RESULTS: Of 20789 pediatric TB cases, 5162 (24.8%) had bacteriologically confirmed TB. Among 4826 (93.5%) with drug susceptibility testing, 82 (1.7%) had MDR-TB. Most pediatric MDR-TB cases were female (n = 51 [62%]), median age was 5 years (interquartile range, 1-12 years), one-third were Hispanic (n = 28 [34%]), and two-thirds (n = 55 [67%]) were born in the United States. Most cases had additional resistance to ≥1 other first-line drug (n = 66 [81%]) and one-third had resistance to ≥1 second-line drug (24/73 tested). Of 77 who started treatment prior to 2013, 66 (86%) completed treatment and 4 (5%) died. Among the 4 high-TB-burden states/jurisdictions surveyed, there was 42%-55% underestimation of pediatric MDR-TB cases when using only culture-confirmed case definitions. CONCLUSIONS: Only one-quarter of pediatric TB cases had culture-confirmed TB, likely resulting in underestimation of true pediatric MDR-TB burden in the United States using strictly bacteriologic criteria. Better estimates of pediatric MDR-TB burden in the United States are needed and should include clinical diagnoses based on epidemiologic criteria.

Cutaneous metastasis to the scalp as the primary presentation of colorectal adenocarcinoma.

Eruptaneous metastasis is an uncommon presentation of colorectal adenocarcinoma that can occur years after diagnosis of the primary cancer or manifest as the first sign of malignancy. It is essential to diagnose these metastases immediately, as this late-stage development carries a poor prognosis. The scalp is one of the less common sites for skin metastases and nodules may be mistaken for benign entities. In this case report, we report on the case of a 61-year-old woman with CREST syndrome who presented with a cutaneous metastasis to the scalp as the first sign ofcolorectal adenocarcinoma.

Infected animal models for tissue engineering.

Infection is one of the most common complications associated with medical interventions and implants. As tissue engineering strategies to replace missing or damaged tissue advance, the focus on prevention and treatment of concomitant infection has also begun to emerge as an important area of research. Because the in vivo environment is a complex interaction between host tissue, implanted materials, and native immune system that cannot be replicated in vitro, animal models of infection are integral in evaluating the safety and efficacy of experimental treatments for infection. In this review, considerations for selecting an animal model, established models of infection, and areas that require further model development are discussed with regard to cutaneous, fascial, and orthopedic infections.

Modulation of polyplex release from biodegradable microparticles through poly(ethylenimine) modification and varying loading concentration.

PURPOSE: This work investigates the effects of hyaluronic acid (HA) conjugated onto branched poly(ethylenimine) (bPEI) and varying loading concentrations of these polymers complexed with DNA on their release from poly(DL-lactic-co-glycolic acid) (PLGA) microparticles and the transfection of target cells. METHODS: To examine the effect of alteration of the gene delivery polymer on the system, we observed the morphology, size, loading efficiency, polymer and DNA release, and the transfection efficiency for the microparticles formed with three internal phase loading concentrations during microparticle formation. RESULTS: Addition of HA to this vector allowed for increased loading concentration within these systems and significantly altered release kinetics without changing the morphology of the particles. The incorporation of HA onto the bPEI backbone significantly increased the transfection efficiency of the complexes released from the corresponding microparticle formulation. CONCLUSIONS: The results show that the modification of bPEI with HA and the concentration of loaded polymer/DNA complexes can significantly alter the entrapment and release profiles from PLGA microparticles. This is significant in that it offers insight into the effects of modification of gene delivery vectors on a controlled release system designed to achieve a sustained therapeutic response.

Effects of antibiotic physicochemical properties on their release kinetics from biodegradable polymer microparticles.

PURPOSE: This study investigated the effects of the physicochemical properties of antibiotics on the morphology, loading efficiency, size, release kinetics, and antibiotic efficacy of loaded poly(DL-lactic-co-glycolic acid) (PLGA) microparticles (MPs) at different loading percentages. METHODS: Cefazolin, ciprofloxacin, clindamycin, colistin, doxycycline, and vancomycin were loaded at 10 and 20 wt% into PLGA MPs using a water-in-oil-in water double emulsion fabrication protocol. Microparticle morphology, size, loading efficiency, release kinetics, and antibiotic efficacy were assessed. RESULTS: The results from this study demonstrate that the chemical nature of loaded antibiotics, especially charge and molecular weight, influence the incorporation into and release of antibiotics from PLGA MPs. Drugs with molecular weights less than 600 Da displayed biphasic release while those with molecular weights greater than 1,000 Da displayed triphasic release kinetics. Large molecular weight drugs also had a longer delay before release than smaller molecular weight drugs. The negatively charged antibiotic cefazolin had lower loading efficiency than positively charged antibiotics. Microparticle size appeared to be mainly controlled by fabrication parameters, and partition and solubility coefficients did not appear to have an obvious effect on loading efficiency or release. Released antibiotics maintained their efficacy against susceptible strains over the duration of release. Duration of release varied between 17 and 49 days based on the type of antibiotic loaded. CONCLUSIONS: The data from this study indicate that the chemical nature of antibiotics affects properties of antibiotic-loaded PLGA MPs and allows for general prediction of loading and release kinetics.

Intensified specimen collection to improve tuberculosis diagnosis in children from Rural South Africa, an observational study.

BACKGROUND: In drug-resistant TB settings, specimen collection is critical for drug-susceptibility testing (DST). This observational study included multiple specimen types collected from pediatric TB suspects with the aim to determine diagnostic yield and inform clinical practice in children with drug-resistant and drug-susceptible TB. METHODS: From 03/2009-07/2010, TB suspects aged ≥6 months and ≤12 years were recruited among outpatient and inpatient settings. Subjects were new TB suspects or had persistent symptoms despite ≥2 months of TB treatment. The protocol included collection of a single blood and urine specimen, a single sputum induction and, if inpatients and <5 years of age, collection of 3 gastric aspirates (GA). Samples were cultured on solid and/or liquid media. DST was by 1% proportion method. RESULTS: Among 118 children with possible, probable or confirmed TB, the mean age was 4.9 years [SD 3.2] and 64 (62%) of those tested were HIV-positive. Eight (7%) subjects were culture-positive from at least one specimen; yield did not differ by HIV status or TB treatment history. Among those with positive cultures, 7/8 (88%) were from induced sputum, 5/6 (83%) from GA, 3/8 (38%) from blood, and 3/7 (43%) from urine. In subjects with both induced sputum and GA collection, sputum provided one additional case compared to GA. Multidrug resistant (MDR)-TB was detected by urine culture alone in one child >5 years old. Pan-resistant extensively drug resistant (XDR)-TB was identified by cultures from all sites in one subject. CONCLUSIONS: TB was cultured from HIV-positive and -negative children, and allowed for identification of MDR and XDR-TB cases. Urine and induced sputum each provided an additional TB diagnosis and, when compared to GA, may be considered a less invasive, same-day method of specimen collection for childhood TB suspects. This study illustrates the continued challenges and limitations of available strategies for pediatric TB diagnostics.

A capture-recapture modeling framework emphasizing expert opinion in disease surveillance.

In disease surveillance, capture-recapture methods are commonly used to estimate the number of diseased cases in a defined target population. Since the number of cases never identified by any surveillance system cannot be observed, estimation of the case count typically requires at least one crucial assumption about the dependency between surveillance systems. However, such assumptions are generally unverifiable based on the observed data alone. In this paper, we advocate a modeling framework hinging on the choice of a key population-level parameter that reflects dependencies among surveillance streams. With the key dependency parameter as the focus, the proposed method offers the benefits of (a) incorporating expert opinion in the spirit of prior information to guide estimation; (b) providing accessible bias corrections, and (c) leveraging an adapted credible interval approach to facilitate inference. We apply the proposed framework to two real human immunodeficiency virus surveillance datasets exhibiting three-stream and four-stream capture-recapture-based case count estimation. Our approach enables estimation of the number of human immunodeficiency virus positive cases for both examples, under realistic assumptions that are under the investigator's control and can be readily interpreted. The proposed framework also permits principled uncertainty analyses through which a user can acknowledge their level of confidence in assumptions made about the key non-identifiable dependency parameter.

Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against Wuhan-WT, delta and omicron BA1, BA2 spike trimers.

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of human angiotensin converting enzyme 2 (hACE-2) binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using Wuhan-WT (vaccine strain), delta (B.1.167.2), omicron BA1 and BA2 variant viral strains showed strong correlation with cell-based pseudovirus neutralization activity (PNA) and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta and omicron variant resistance to neutralization in samples with paired vaccine strain and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. Importantly, this completely automated assay can be performed in 4 h to measure neutralizing antibody titers for 16 samples over 8 serial dilutions or, 128 samples at a single dilution with replicates. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.

Old drugs, new purpose: retooling existing drugs for optimized treatment of resistant tuberculosis.

Treatment of drug-resistant tuberculosis is hindered by the high toxicity and poor efficacy of second-line drugs. New compounds must be used together with existing drugs, yet clinical trials to optimize combinations of drugs for drug-resistant tuberculosis are lacking. We conducted an extensive review of existing in vitro, animal, and clinical studies involving World Health Organization-defined group 1, 2, and 4 drugs used in drug-resistant tuberculosis regimens to inform clinical trials and identify critical research questions. Results suggest that optimizing the dosing of pyrazinamide, the injectables, and isoniazid for drug-resistant tuberculosis is a high priority. Additional pharmacokinetic, pharmacodynamic, and toxicodynamic studies are needed for pyrazinamide and ethionamide. Clinical trials of the comparative efficacy and appropriate treatment duration of injectables are recommended. For isoniazid, rapid genotypic tests for Mycobacterium tuberculosis mutations should be nested in clinical trials. Further research focusing on optimization of dose and duration of drugs with activity against drug-resistant tuberculosis is paramount.

Use of surveillance data to elucidate household clustering of SARS-CoV-2 in Fulton County, Georgia a major metropolitan area.

BACKGROUND: Households are important for SARS-CoV-2 transmission due to high intensity exposure in enclosed spaces over prolonged durations. We quantified and characterized household clustering of COVID-19 cases in Fulton County, Georgia. METHODS: We used surveillance data to identify all confirmed COVID-19 cases in Fulton County. Household clustered cases were defined as cases with matching residential address. We described the proportion of COVID-19 cases that were clustered, stratified by age over time and explore trends in age of first diagnosed case within households and subsequent household cases. RESULTS: Between June 1, 2020 and October 31, 2021, 31,449(37%) of 106,233 cases were clustered in households. Children were the most likely to be in household clusters than any other age group. Initially, children were rarely (∼ 10%) the first cases diagnosed in the household but increased to almost 1 of 3 in later periods. DISCUSSION: One-third of COVID-19 cases in Fulton County were part of a household cluster. Increasingly children were the first diagnosed case, coinciding with temporal trends in vaccine roll-out among the elderly and the return to in-person schooling in Fall 2021. Limitations include restrictions to cases with a valid address and unit number and that the first diagnosed case may not be the infection source for the household.

Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against native-like vaccine and delta variant spike trimers.

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.

Toward Ending the HIV Epidemic: Temporal Trends and Disparities in Early ART Initiation and Early Viral Suppression Among People Newly Entering HIV Care in the United States, 2012-2018.

Background: In 2012, the US Department of Health and Human Services updated their HIV treatment guidelines to recommend antiretroviral therapy (ART) for all people with HIV (PWH) regardless of CD4 count. We investigated recent trends and disparities in early receipt of ART prescription and subsequent viral suppression (VS). Methods: We examined data from ART-naïve PWH newly presenting to HIV care at 13 North American AIDS Cohort Collaboration on Research and Design clinical cohorts in the United States during 2012-2018. We calculated the cumulative incidence of early ART (within 30 days of entry into care) and early VS (within 6 months of ART initiation) using the Kaplan-Meier survival function. Discrete time-to-event models were fit to estimate unadjusted and adjusted associations of early ART and VS with sociodemographic and clinical factors. Results: Among 11 853 eligible ART-naïve PWH, the cumulative incidence of early ART increased from 42% in 2012 to 82% in 2018. The cumulative incidence of early VS among the 8613 PWH who initiated ART increased from 83% in 2012 to 93% in 2018. In multivariable models, factors independently associated with delayed ART and VS included non-Hispanic/Latino Black race, residence in the South census region, being a male with injection drug use acquisition risk, and history of substance use disorder (SUD; all P ≤ .05). Conclusions: Early ART initiation and VS have substantially improved in the United States since the release of universal treatment guidelines. Disparities by factors related to social determinants of health and SUD demand focused attention on and services for some subpopulations.

Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against native-like vaccine and delta variant spike trimers.

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.